Original
Clinicopathologic features and treatment response in nephrotic IgA nephropathy with minimal change disease
Jing Qin, Qiongqiong Yang, Xueqing Tang, Wenfang Chen, Zhibin Li, Haiping Mao, Zongpei Jiang, Fengxian Huang and Xueqing Yu
Price
42.00 $
Volume 79 (2013) p. 37 - 44
Abstract
Clinicopathologic features and treatment response in nephrotic IgA nephropathy with minimal change disease
Jing Qin1,2*, Qiongqiong Yang1,2*, Xueqing Tang1,2, Wenfang Chen3, Zhibin Li4, Haiping Mao1,2, Zongpei Jiang1,2, Fengxian Huang1,2 and Xueqing Yu1,2
1Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 2Key Laboratory of Nephrology, Ministry of Health, Guangzhou, Guangdong, 3Department of Pathology and 4Epidemiology and Clinical Research Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
*Both of the authors contributed equally to this work.
Objective: To analyze the clinicopathological features and therapeutic response of nephrotic IgA nephropathy (IgAN) patients with minimal-change disease (MCD). Methods: 62 nephrotic IgAN patients were enrolled between January 2002 and December 2008, and divided into two groups including Group A: patients with MCD-like pathological features, and Group B with non-MCD pathologic pattern. The clinicopathological features, treatments, and responses were then analyzed. Results: 13 (21.0%) patients exhibited MCD-like pathological changes. Patients in Group A presented more prominent proteinuria, hypoalbuminemia but higher hemoglobin and no incidence of renal insufficiency compared to Group B (p < 0.05). 62 patients were treated with corticosteroid, and the complete remission rate in Group A is higher than that in Group B (84.6% vs. 34.7%, p = 0.008), but the relapse rate is much higher in Group A (53.8% vs. 20.4%, p = 0.03). 21 patients were treated combining with immunosuppressant due to unresponsiveness or relapse, which yielded a high re-remission rate in Group A (100%). After follow-up of 53.9 ± 26.9 months, the 5-year renal survival rate is higher in Group A (100%) than that in Group B (84.7%), but no significant difference was observed (p = 0.24). Conclusions: MCD-like pathological changes exist in quite a few nephrotic IgAN patients. These IgAN patients responded well to corticosteroid monotherapy but had a higher rate of relapse. Though manifesting with severe nephrotic symptoms, they tended to have a favorable clinical outcome probably due to the minimal pathological changes. Nevertheless, larger sample size and longer follow-up periods are needed for better understanding of the disease.Correspondence to:
Dr. Xueqing Yu
Department of Nephrology
The First Affiliated Hospital
Sun Yat-sen University
Guangzhou 510080, China
Email: [email protected]
Original
Population pharmacokinetics of adefovir dipivoxil tablets in healthy Chinese volunteers
Jihan Huang, Yaping Zhang, Xiaohui Huang, Lujin Li, Yunfei Li, Kun Wang, Juan Yang, Yingchun He, Yinghua Lv, and Qingshan Zheng
Price
42.00 $
Volume 52 p. 8 - 14
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 1/2014 (8-14)
Population pharmacokinetics of adefovir dipivoxil tablets in healthy Chinese volunteers
Jihan Huang1*, Yaping Zhang2*, Xiaohui Huang3, Lujin Li1, Yunfei Li1, Kun Wang1,2, Juan Yang1, Yingchun He1, Yinghua Lv1, and Qingshan Zheng1
1Department of Pharmacometrics, Center for Drug Clinical Research, Shanghai University of Chinese Medicine, Shanghai, China, 2Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA, and 3Department of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Hefei, Anhui, China
Aim: To develop a population pharmacokinetic model of adefovir dipivoxil in healthy volunteers and evaluate the effect of individual factors on the pharmacokinetics of adefovir dipivoxil. Methods: Plasma concentration data collected from 32 healthy Chinese subjects in a Phase I clinical study was pooled. Subjects received a single oral dose of 10 mg, 20 mg, or 30 mg adefovir dipivoxil, or multiple doses of 10 mg once a day for 9 days. Plasma concentrations of adefovir dipivoxil were measured using a validated liquid chromatography-mass spectrometric method. A nonlinear mixed-effect model was used to analyze the plasma concentration data of adefovir dipivoxil in healthy volunteers and to calculate the relevant parameters as well as inter- and intra-individual variability. Results: The time course of adefovir dipivoxil concentration is best described by a firstorder absorption and first-order elimination two-compartment model with lag time. The final estimate of total body clearance (CL) is 56.9 L/h and 78.7 L/h for single and multiple dosing regimen, respectively; the volume distribution of the central compartment (V2) is 106 L; inter-compartmental clearance (Q) is 220 L/h; volume distribution of the peripheral compartment (V3) is 498 L and 800 L for single and multiple dosing regimen, respectively; absorption rate is 0.509 h–1; and lag time is 0.315 hours. The inter-individual variabilities of CL and V2 were 22.4% and 58.9%, respectively. The proportional error of residual variability is 14.1% and the additive error is 0.30 ng/L. The final pharmacokinetic model was evaluated using a bootstrap method. Conclusions: A nonlinear mixed effect model for oral adefovir dipivoxil formulations was developed in healthy Chinese subjects. A multiple dosing regimen may significantly increase the body clearance and volume distribution of the peripheral compartment compared to a single dosing regimen.
*These authors contribute equally to this work.Correspondence to:
Dr. Kun Wang
Department of pharmacometrics
Center for Drug Clinical Research
Shanghai University of Chinese Medicine
Shanghai 20123, China
Email: [email protected]
Original
Pharmacokinetics of single-dose morinidazole in patients with severe renal impairment
Hao Zhang, Lu Huang, Yuan-yuan Huang, Bin Yi, Qi Pei, Hong-yi Tan, Jie Huang, Ji-shi Liu, Hong Yuan, and Guo-ping Yang
Price
42.00 $
Volume 52 p. 159 - 165
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 2/2014 (159-165)
Pharmacokinetics of single-dose morinidazole in patients with severe renal impairment
Hao Zhang2, Lu Huang1,3, Yuan-yuan Huang1, Bin Yi2, Qi Pei1, Hong-yi Tan1, Jie Huang1, Ji-shi Liu2, Hong Yuan1, and Guo-ping Yang1
1Center of Clinical Pharmacology, 2Department of Nephrology, the Third Xiangya Hospital, and 3College of Pharmacy, Central South University, Changsha, Hunan, China
Objective: To evaluate the pharmacokinetics of morinidazole in individuals with severe renal impairment (RI). Methods: This open-label Phase I study enrolled healthy volunteers and patients with severe RI aged 18 – 65 years. All subjects received a single infusion of sodium chloride injection with 500 mg morinidazole. Plasma and urine concentration of morinidazole and one of its metabolites (M4-1) were evaluated by using HPLC-UV and HPLC-MS/MS respectively. Pharmacokinetic parameters were calculated by Phoenix WinNonlin 6.0 software. Results: 22 individuals (healthy: n = 11, severe RI: n = 11) received morinidazole. In both groups, maximum plasma concentration of morinidazole was reached within 1 hour, while the tmax of M4-1 differed greatly. Both AUC0–t and AUC0–∞ of morinidazole were 1.4 times higher in patients with severe RI, while M4-1 were over 7 times higher than healthy groups. Renal excretion of unchanged morinidazole was decreased by 65% in patients with RI, and M4-1 was decreased by 72%. Apparent correlation between CLcr and CL, AUC, t1/2 and CLr were seen in two groups. Conclusions: A single dose of 500 mg morinidazole is well tolerated. Changes in pharmacokinetic parameters of morinidazole and M4-1 are seen in patients with RI and may be clinically important.Correspondence to:
Prof. Guoping Yang
Center of Clinical Pharmacology, Third Xiangya Hospital
Central South University
Changsha, Hunan 410013, China
Email: [email protected]
Original
Warfarin compared with aspirin for older Chinese patients with stable coronary heart diseases and atrial fibrillation complications
Xinbing Liu, Hongman Huang, Jianhua Yu, Guoliang Cao, Liuliu Feng, Qitan Xu, Shufu Zhang, Mingcheng Zhou, and Yigang Li
Price
42.00 $
Volume 52 p. 454 - 459
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 6/2014 (454-459)
Warfarin compared with aspirin for older Chinese patients with stable coronary heart diseases and atrial fibrillation complications
Xinbing Liu1, Hongman Huang1, Jianhua Yu1, Guoliang Cao2, Liuliu Feng1, Qitan Xu1, Shufu Zhang1, Mingcheng Zhou3, and Yigang Li4
1Department of Cardiology, Shanghai Shi Dong Hospital, 2Department of Geriatrics, Shanghai No. 3 People’s Hospital, 3Department of Cardiology, An Tu Hospital, and 4Department of Cardiology, Xin Hua Hospital, Shanghai, China
Objective: To compare the therapeutic warfarin and aspirin efficacies for treatments of atrial fibrillation (AF) complicated with stable coronary heart disease particularly in older Chinese patients. Methods: In our prospective study 101 patients with AF and stable coronary heart disease older than 80 years were randomized into two groups. One group (n = 51) basically received 1.25 mg/day warfarin per os, followed by addition of 0.5 – 1.0 mg/day from day 3 – 5 if the international normalized ratio (INR) was initially < 1.5 and in order to achieve a maintained INR between 1.6 and 2.5 (warfarin group). The second group (n = 50) received 100 mg aspirin per day (control group). All patients were medicated and monitored for a period of 2 years. The primary endpoint was the occurrence of ischemic stroke or systemic embolism, and the composite secondary endpoint was non-fatal myocardial infarction and all causes of death. For safety evaluation, the hemorrhage rates were recorded. Results: The warfarin medication was superior regarding the overall occurrence of ischemic stroke or systemic embolism as well as non-fatal myocardial infarction and all causes of death outcomes compared to aspirin administration during the 2 years of medication (17.6% vs. 36.0%, p = 0.03), while there was no significant difference of mild (5 vs. 4), severe (2 vs. 1), and fatal (1 vs. 1) hemorrhage incidences between the warfarin and aspirin groups (p > 0.05). Conclusion: Warfarin was found to be more efficacious than aspirin for an anticoagulation therapy of older Chinese patients with AF and stable coronary heart disease.Correspondence to:
Mingcheng Zhou
Department of Cardiology, An Tu Hospital
No. 200 Yanji East Road, Shanghai, 200093, China
Email: [email protected]
Original
IgA nephropathy with anti-neutrophil cytoplasmic antibody seropositivity
Xin Huang, Yuan Wang, Lijiao Xie, Ying Zhang, Sha Tang, Shiwei Yin, Xuejing Gao, Juan Cai, Weili Wang, Jun Zhang, Jinghong Zhao, Yunjian Huang, Yafei Li, and Jingbo Zhang
Price
42.00 $
Volume 84 (2015) p. 156 - 164
Abstract
Clinical Nephrology, Vol. 84 – No. 3/2015 (156-164)
IgA nephropathy with anti-neutrophil cytoplasmic antibody seropositivity
Xin Huang*1, Yuan Wang*1, Lijiao Xie1, Ying Zhang1, Sha Tang1, Shiwei Yin1, Xuejing Gao1, Juan Cai1, Weili Wang1, Jun Zhang1, Jinghong Zhao1, Yunjian Huang1, Yafei Li2, and Jingbo Zhang1
1Department of Nephrology, Xinqiao Hospital, and 2Department of Epidemiology in College of Preventive Medicine, Third Military Medical University, Chongqing, China
Background: There are few reports of IgA nephropathy (IgAN) with antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. Methods: The authors report the clinical and pathological findings in 14 patients with IgAN and ANCA seropositivity. Results: These retrospective cases consisted of 4 men and 10 women with a mean age of 44.4 ± 12.7 years. ANCA-positivity was documented by EUROBlot kits and indirect immunofluorescence in all patients. The results of EUROBlot kits were positive in 14 patients (12 MPO-ANCA, 2 PR3-ANCA). Indirect immunofluorescence was positive in 14 patients (12 P-ANCA, 2 C-ANCA). Three of 14 IgAN with ANCA-positive patients showed severe clinical manifestations with crescents involving a mean of 56% glomeruli, including heavy proteinuria (mean 24-hour urine protein: 3.8 g/d), hematuria and acute renal failure (mean creatinine: 4.5 ± 3.7 mg/dL). The remaining 11 patients with no crescents showed various degrees of proteinuria (mean 24-hour urine protein: 2.4 ± 2.4 g/d), hematuria and serum creatinine levels (median creatinine: 0.9 (IQR, 0.5 – 1.4) mg/dL). The follow-up period for 10 patients had an average length of 14.0 ± 11.2 months. Among the three patients with crescents who had been treated with steroids and cyclophosphamide, one patient became dialysis dependent at the time of biopsy and remained on dialysis after treatment, another died of acute heart failure, and the last one showed improvement in renal function after treatment and did not develop end-stage renal disease (ESRD) 26 months after renal biopsy. The remaining 7 patients with no crescents were treated with steroids, cyclophosphamide, renin-angiotensin system inhibitors, and/or Traditional Chinese Medicine; 6 had stabilized or improved renal function and one progressed to ESRD with worsening renal function. Conclusions: These findings suggest not all ANCAs are involved in the pathology of IgAN. In patients with IgAN and ANCAs, identification of pathogenic vs. non-pathogenic ANCAs is recommended.
*These authors contributed equally to this work.Correspondence to:
Dr. Jingbo Zhang
Department of Nephrology, Xinqiao Hospital
Third Military Medical University, Chongqing 400037, China
Email: [email protected]
Original
Clinicopathologic features of IgA nephropathy patients with different levels of proteinuria
Zhen Ai, Ricong Xu, Wenting Liu, Qian Zhou, Bin Li, Fengxian Huang, Xueqing Yu, and Qiongqiong Yang
Price
42.00 $
Volume 86 (2016) p. 35 - 41
Abstract
Clinical Nephrology, Vol. 86 – No. 1/2016 (35-42)
Clinicopathologic features of IgA nephropathy patients with different levels of proteinuria
Zhen Ai1#2, Ricong Xu1#2, Wenting Liu1#2, Qian Zhou3, Bin Li3, Fengxian Huang1#2, Xueqing Yu1#2, and Qiongqiong Yang1#2
1Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 2Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, and 3Epidemiology Research Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Aims: To investigate the clinicopathologic features of IgA nephropathy (IgAN) patients with different levels of proteinuria and its clinical significance. Methods: This was a single-center retrospective cohort study. Patients with biopsy-proven primary IgAN were enrolled from January 2006 to December 2011 in The First Affiliated Hospital of Sun Yat-sen University, divided into six groups based on proteinuria at biopsy (≤ 0.30 g/d, 0.31 – 0.50 g/d, 0.51 – 1.00 g/d, 1.01 – 2.00 g/d, 2.01 – 3.00 g/d, and > 3.00 g/d). Demographic and clinicopathologic data were collected and analyzed. Results: 1,413 patients were enrolled in this study, with the median proteinuria being 0.61 g/d (interquartile range 0.30 – 1.29). Patients with proteinuria > 0.50 g/d showed significant differences in their clinicopathologic characteristics with higher prevalence of hypertension, hypoalbuminemia, hyperuricemia, hypercholesterolemia and hypertriglyceridemia, worse renal function, higher proportions of segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, and interstitial inflammation. Even the patients with proteinuria 0.31 – 0.50 g/d exhibited higher uric acid, lower total serum protein and albumin, higher proportions of crescents, and global glomerulosclerosis. Furthermore, multiple risk factors linear regression analysis has shown that there were significant associations between proteinuria and serum albumin, uric acid, total cholesterol, triglyceride, systolic blood pressure, degrees of segmental glomerulosclerosis, proportions of crescents, and global glomerulosclerosis. Conclusion: Clinicopathologic features were significantly worse in IgAN patients with increasing of proteinuria.Correspondence to:
Qiongqiong Yang MD, PhD, Professor of Medicine
Department of Nephrology, The First Affiliated Hospital
Sun Yat-sen University
58th Zhongshan Road II, Guangzhou 510080, China
Email: [email protected]
Original Research
Advantage of population pharmacokinetic method for evaluating the bioequivalence and accuracy of parameter estimation of pidotimod
Jihan Huang, Mengying Li, Yinghua Lv, Juan Yang, Ling Xu, Jingjing Wang, Junchao Chen, Kun Wang, Yingchun He, and Qingshan Zheng
Price
42.00 $
Volume 54 p. 682 - 692
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 9/2016 (682-692)
Advantage of population pharmacokinetic method for evaluating the bioequivalence and accuracy of parameter estimation of pidotimod
Jihan Huang*, Mengying Li*, Yinghua Lv, Juan Yang, Ling Xu, Jingjing Wang, Junchao Chen, Kun Wang, Yingchun He, and Qingshan Zheng
Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Objective: This study was aimed at exploring the accuracy of population pharmacokinetic method in evaluating the bioequivalence of pidotimod with sparse data profiles and whether this method is suitable for bioequivalence evaluation in special populations such as children with fewer samplings. Methods: In this single-dose, two-period crossover study, 20 healthy male Chinese volunteers were randomized 1 : 1 to receive either the test or reference formulation, with a 1-week washout before receiving the alternative formulation. Noncompartmental and population compartmental pharmacokinetic analyses were conducted. Simulated data were analyzed to graphically evaluate the model and the pharmacokinetic characteristics of the two pidotimod formulations. Various sparse sampling scenarios were generated from the real bioequivalence clinical trial data and evaluated by population pharmacokinetic method. Results: The 90% confidence intervals (CIs) for AUC0–12h, AUC0–∞, and Cmax were 97.3 – 118.7%, 96.9 – 118.7%, and 95.1 – 109.8%, respectively, within the 80 – 125% range for bioequivalence using noncompartmental analysis. The population compartmental pharmacokinetics of pidotimod were described using a one-compartment model with first-order absorption and lag time. In the comparison of estimations in different dataset, the estimation of random three- and< fixed four-point sampling strategies can provide results similar to those obtained through rich sampling. The nonlinear mixed-effects model requires fewer data points. Moreover, compared with the noncompartmental analysis method, the pharmacokinetic parameters can be more accurately estimated using nonlinear mixed-effects model. Conclusions: The population pharmacokinetic modeling method was used to assess the bioequivalence of two pidotimod formulations with relatively few sampling points and further validated the bioequivalence of the two formulations. This method may provide useful information for regulating bioequivalence evaluation in special populations.
*Jihan Huang and Mengying Li contributed equally to this work.Correspondence to:
Kun Wang, MD
or
Yingchun He
Center for Drug Clinical Research
Shanghai University of Traditional Chinese Medicine
1200#, Cailun Rd, Pudong New District, Shanghai, 201203, China
Email: [email protected] or [email protected]
Original
Long-term renal outcomes of IgA nephropathy presenting with different levels of proteinuria
Zhen Ai, Qian Zhou, Fengxian Huang, Qiongqiong Yang, and Xueqing Yu
Price
42.00 $
Volume 94 (2020) p. 290 - 296
Abstract
Clinical Nephrology, Vol. 94 – No. 6/2020 (290-296)
Long-term renal outcomes of IgA nephropathy presenting with different levels of proteinuria
Zhen Ai1#2, Qian Zhou3, Fengxian Huang1#2, Qiongqiong Yang1#2, and Xueqing Yu1#2
1Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 2Key Laboratory of National Health Commission, Key Laboratory of Guangdong Province, and 3Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Aims: Proteinuria is a strong prognostic factor in IgA nephropathy (IgAN). However, the risk threshold of proteinuria for kidney disease progression remains in debate. This study aimed to evaluate the risk of different levels of proteinuria on renal outcomes in Chinese patients with IgAN.
Materials and methods: Patients with biopsy-proven primary IgAN were recruited and divided into four groups based on their proteinuria levels: ≤ 0.30 g/d, 0.31 – 0.50 g/d, 0.51 – 1.00 g/d, and > 1.00 g/d. The primary outcomes were composed by doubling of baseline serum creatinine (Scr) and end-stage renal disease (ESRD, defined as eGFR < 15 mL/min/1.73m2, initiation of dialysis or transplantation).
Results: A total of 921 IgAN patients were enrolled in this study. During a median follow-up duration of 48 (34 – 62) months, higher risks of doubling of baseline Scr developed in patients with proteinuria 0.31 – 0.50 g/d (HR = 2.87, p = 0.04), 0.51 – 1.00 g/d (HR = 4.26, p = 0.002), and > 1.00 g/d (HR = 14.56, p < 0.001), while increased risks for ESRD were observed in patients with proteinuria 0.51 – 1.00 g/d (HR = 3.00, p = 0.02) and > 1.00 g/d (HR = 13.03, p < 0.001) in unadjusted Cox regression models. After adjusted for potential confounders, proteinuria 0.31 – 0.50 g/d (HR = 3.70, p = 0.04), 0.51 – 1.00 g/d (HR = 3.67, p = 0.02), and > 1.00 g/d (HR = 8.20, p < 0.001) remained to be significantly associated with higher risks of doubling of Scr, while only those with proteinuria > 1.00 g/d (HR = 6.04, p = 0.001) exhibited a markedly increased risk of ESRD.
Conclusion: Patients with proteinuria levels > 0.30 g/d already have a higher risk of doubling of baseline Scr, suggesting the necessity of early intervention in patients presenting with minimal proteinuria.Correspondence to:
Prof. Xueqing Yu, MD, PhD
Department of Nephrology
The First Affiliated Hospital, Sun Yat-sen University
58th Zhongshan Road II, Guangzhou,
Guangdong 510080, China
Email: [email protected]
Bioavailability Section
A UPLC-MS/MS method for simultaneous quantification of sildenafil and N-desmethyl sildenafil applied in pharmacokinetic and bioequivalence studies in a Chinese population
Jie Huang, Hualin Cai, Wenqun Li, Xiaomei Huang, Huiyu Guan, Xi Wang, Yamin Yin, Binbin He, Jian Huang, and Bikui Zhang
Price
42.00 $
Volume 59 (2021) p. 164 - 174
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 59 – No. 2/2021 (164-174)
A UPLC-MS/MS method for simultaneous quantification of sildenafil and N-desmethyl sildenafil applied in pharmacokinetic and bioequivalence studies in a Chinese population
Jie Huang1#2, Hualin Cai1#2, Wenqun Li1#2, Xiaomei Huang3, Huiyu Guan3, Xi Wang3, Yamin Yin3, Binbin He3, Jian Huang3, and Bikui Zhang1#2
1Department of Pharmacy, The Second Xiangya Hospital, 2Institute of Clinical Pharmacy, Central South University, and 3Xiangya Boai Rehabilitation Hospital, Changsha, China
Objective: To evaluate the pharmacokinetic parameters and bioequivalence of two sildenafil tablets (20 mg) in healthy Chinese subjects.
Materials and methods: A random, crossover, self-control design was used. 20 healthy subjects including males and females were randomized into two groups. A single oral dose of the trial or reference preparation was given to the two groups of subjects after an overnight fast of 10 hours. Blood samples were taken at scheduled time points. Plasma concentrations of sildenafil and N-desmethyl sildenafil were measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). ANOVA was used to check the difference of the mean values of the pharmacokinetic parameters between the two preparations. Bioequivalence was determined by two one-sided t-tests and 90% confidence intervals.
Results: The quantitative range of sildenafil and N-desmethyl sildenafil was 2.000 – 200.0 ng/mL and 0.800 – 80.00 ng/mL, respectively. Plasma samples were stable, and there was no mutual interference between the analyte and internal standard. With the 90% confidence limit, the trial preparations AUC0→t and Cmax fall within 80.00 – 125.00% of the reference preparation’s AUC0→t and Cmax. The tmax of sildenafil and N-desmethyl sildenafil was ~ 0.9 hours and 1 hour, and the T1/2 was 2.4 hours and 3.7 hours, respectively. The relative bioavailability of sildenafil and N-desmethyl sildenafil was 99.28 ± 3.30% and 99.20 ± 3.39%. No significant difference was found in every factor between the trial preparation and the reference preparation.
Conclusion: The UPLC-MS/MS method was successfully established to evaluate the pharmacokinetic parameters of sildenafil in healthy Chinese subjects. The trial preparation was bioequivalent to the reference preparation.Correspondence to:
Prof. Bikui Zhang
Department of Pharmacy
The Second Xiangya Hospital
Central South University, Changsha 410000, China
Email: [email protected]
Case
Report
Hepatic failure with fatal outcome during pregnancy following administration of a single therapeutic dose of acetominophen: Case report and literature review
Yu Gao, Rui Zhang, Hua Liang, and Yan Huang
Price
42.00 $
Volume 60 (2022) p. 486 - 491
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 60 – No. 11/2022 (486-491)
Hepatic failure with fatal outcome during pregnancy following administration of a single therapeutic dose of acetominophen: Case report and literature review
Yu Gao, Rui Zhang, Hua Liang, and Yan Huang
Department of Pharmacy, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
Acetaminophen is generally regarded as a safe antipyretic and analgetic agent and is widely used in cases of pregnancy. However, acetaminophen is also one of the most frequently reported medications in cases of drug overdose. On the other hand, in the few instances described in the literature, where normal doses of acetaminophen administered during pregnancy may have had a fatal outcome, evidence existed pointing to a history of liver disease. It is therefore of interest that the patient in this report who died of liver failure after ingesting standard doses of acetaminophen also suffered from intrahepatic cholestasis during pregnancy although there was no history of liver disease. Other than these instances, there have been no previous reports in the literature of a normal, therapeutic dose of acetaminophen having a fatal outcome in pregnancy. This case emphasizes the need for caution when prescribing acetaminophen during pregnancy to patients with a history of liver disease, regardless of whether the liver function has returned to normal.
Correspondence to:
Rui Zhang, MD
Department of Pharmacy
Chengdu Women’s and Children’s Central Hospital
School of Medicine
University of Electronic Science and Technology of China
NO.1617 Riyue Avenue, Qingyang District
Chengdu, Sichuan Province, China
Email: [email protected]
Bioavailability Section
Pharmacokinetics and bioequivalence of two methylprednisolone tablet formulations in healthy Chinese subjects under fasting and fed conditions
Lianlian Fan, Peiwen Zhang, Chunyan Gan, Qian Huang, Zhen Shen, Xue Xiao, Ying Yang, Daicong Qiu, Gang Mai, and Jianzhong Shentu
Price
42.00 $
Volume 61 (2023) p. 37 - 44
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 61 – No. 1/2023 (37-44)
Pharmacokinetics and bioequivalence of two methylprednisolone tablet formulations in healthy Chinese subjects under fasting and fed conditions
Lianlian Fan1*, Peiwen Zhang1*, Chunyan Gan1, Qian Huang1, Zhen Shen1, Xue Xiao1, Ying Yang1, Daicong Qiu1, Gang Mai1, and Jianzhong Shentu1#2
1Phase 1 Clinical Trial Center, Deyang People’s Hospital, Deyang, and 2Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
Aims: The aims of this study were to evaluate and compare the pharmacokinetic profiles and bioequivalence of two tablet formulations of methylprednisolone (test formulation: Zhejiang Xianju Pharmaceutical Co., Ltd., China; reference formulation: Medrol, Pfizer Italia SRL) in healthy Chinese subjects under fasting and fed conditions.
Materials and methods: Subjects were randomly allocated to either the fasting group or the fed group and also to one of two sequences (test-reference or reference-test), according to which they received a single 16-mg dose of the test or reference methylprednisolone tablet in the study periods. Blood samples were collected pre dose and at intervals up to 16 hours after administration. Plasma methylprednisolone concentrations were determined using a validated liquid chromatography tandem mass spectrometry method. The safety of the medications was monitored throughout the study. The primary pharmacokinetic parameters measured were Cmax, AUC0–t, and AUC0–∞.
Results: A total of 56 subjects were enrolled, and all completed the study. The 90% confidence intervals for Cmax, AUC0–t, and AUC0–∞, measured under both fasting and fed conditions, fell within the acceptable range for bioequivalence of 80 – 125%. Analysis of variance showed that there were no significant differences in the primary pharmacokinetic parameters (Cmax, AUC0–t, and AUC0–∞) between the test and reference formulation measured under both fasted and fed conditions. No serious or unexpected adverse drug reactions occurred during the study period.
Conclusion: The test methylprednisolone 16 mg tablet produced in China is bioequivalent to the reference formulation (Medrol) in healthy Chinese subjects measured under both fasting and fed conditions. Both formulations were well tolerated by all study participants.
*The authors contributed equally to this study and shared first authorship.Correspondence to:
Jianzhong Shentu, MD, PhD
#79 Qingchun Road
Hangzhou, Zhejiang Province, China, 31003
or
Gang Mai, MD
#173 Taishan Road North
Jingyang District, Deyang,
Sichuan Province, 618000, China
Email: [email protected]; [email protected]
Bioavailability Section
Bioequivalence study of domperidone dry suspension in healthy Chinese subjects under fasted and fed conditions: An open-label, randomized, single-dose, crossover trial
Lihua Wu, Qian Huang, Meihua Lin, Jiejing Kai, Yujie Huang, You Zhai, Jian Liu, and Jianzhong Shentu
Price
42.00 $
Volume 61 (2023) p. 320 - 328
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 61 – No. 7/2023 (320-328)
Bioequivalence study of domperidone dry suspension in healthy Chinese subjects under fasted and fed conditions: An open-label, randomized, single-dose, crossover trial
Lihua Wu1, Qian Huang2, Meihua Lin2, Jiejing Kai2, Yujie Huang2, You Zhai2, Jian Liu2, and Jianzhong Shentu2
1Phase I Clinical Trial Center, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University, Shulan International Medical College, and 2Research Center for Clinical Pharmacy, Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
Background: Domperidone has long been used as a prokinetic agent in the treatment of epigastric distress symptoms. This study aimed to provide adequate evidence for registration approval of a new generic dry suspension formulation of domperidone by comparing the safety and pharmacokinetic profiles between the test and branded reference formulation in the context of fasted and fed condition.
Materials and methods: This was designed as a randomized, open-label, single-dose, two-period, two-treatment crossover study. 32 and 28 eligible healthy subjects were enrolled in the fasted and fed study, respectively. Each subject was randomly assigned to receive either the test or reference formulation in the first period, followed by a 1-week washout period and dosing of the alternate formulation in the second period. A series of blood samples were collected at scheduled timepoints within 48 hours after administration during each treatment period. Plasma concentrations of domperidone were determined by validated HPLC-MS/MS. Pharmacokinetic parameters, including Cmax, tmax, AUC0–t, AUC0–∞, and T1/2, were acquired based on the concentration vs. time profiles by non-compartmental analysis using WinNonlin software. Then the geometric mean ratios (GMR) of Cmax, AUC0–t, and AUC0–∞ between the two formulations and corresponding 90% confidence intervals (CIs) were calculated for bioequivalence determination. Safety was assessed as routine.
Results: The two formulations showed similar pharmacokinetic profiles. Under fasted condition, the GMR and corresponding 90% CIs of AUC0–t, AUC0–∞, and Cmax were 101.48% (96.79 – 106.38%), 101.17% (96.66 – 105.90%), and 104.61% (96.73 – 113.14%), respectively. Under fed condition, the GMR and corresponding 90% CIs were 105.46% (99.19 – 112.12%), 104.21% (98.19 – 110.61%), and 112.78% (103.64 – 122.73%), respectively, for AUC0–t, AUC0–∞, and Cmax. All values fell within the accepted bioequivalence range of 80 – 125%. Both the test and the reference products were well tolerated without any serious or unexpected adverse reactions.
Conclusion: Pharmacokinetic bioequivalence was established between the two dry suspension formulations of domperidone in healthy Chinese subjects. Both products were safe and well tolerated.Correspondence to:
Lihua Wu, MD, PhD
Phase I Clinical Trial Center
Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University
Shulan International Medical College
Hangzhou, Zhejiang Province, PR China, 310022
or
Jianzhong Shentu, PhD
Research Center for Clinical Pharmacy
Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research
The First Affiliated Hospital, College of Medicine
Zhejiang University
Hangzhou, Zhejiang Province, PR China, 310003
Email: [email protected]; [email protected]
Nephro
Pharmacology
Comparative analysis of roxadustat efficacy between maintenance hemodialysis and peritoneal dialysis patients
Liling Zhang, Yan Huang, Defeng Yin, Tingting Zhu, Qi Liu, Ying Li, and Linwang Gan
Price
42.00 $
Volume 101 (2024) p. 34 - 42
Abstract
Clinical Nephrology, Vol. 101 – No. 1/2024 (34-42)
Comparative analysis of roxadustat efficacy between maintenance hemodialysis and peritoneal dialysis patients
Liling Zhang1*, Yan Huang1*, Defeng Yin2, Tingting Zhu1, Qi Liu1, Ying Li1, and Linwang Gan1
1Department of Nephrology, 2Department of Emergency, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China
Background: This study evaluated the comparative efficacy of roxadustat for renal anemia between patients on maintenance hemodialysis (HD) and peritoneal dialysis (PD).
Materials and methods: 93 maintenance dialysis patients who regularly followed up from August 2015 to June 2021 were enrolled. Despite receiving a therapeutic dose ≥ 12,000 U/week of erythropoiesis-stimulating agents (E+SA) in the past 12 weeks, this had not worked very well. Subjects were assigned to the HD group (n = 60) or the PD group (n = 33) based on their dialysis treatment modality. All patients received oral roxadustat and were followed up for 24 weeks, after which their hemoglobin, serum iron, transferrin saturation, and ferritin were tested.
Results: We observed that the hemoglobin level of PD patients was significantly increased from 76.1 ± 15.7 g/L to 106 ± 23.8 g/L (p < 0 .001), while it significantly increased from 73.8 ± 12.9 g/L to 100.7 ± 20.2 g/L (p < 0.001) in the HD patients. After 1 and 3 months of roxadustat treatment, the hemoglobin level and its change in the PD group was significantly higher compared to that in the HD group despite the higher dose of roxadustat in the latter group. In addition, roxadustat was noted to reduce cholesterol levels and stabilize serum iron levels in parallel with improving hemoglobin levels.
Conclusion: Roxadustat can effectively increase the hemoglobin level of maintenance dialysis patients, even in those with low erythropoietin response or erythropoietin resistance, and, more importantly, its efficacy in PD patients was more significant.
*Contributed equally.Correspondence to:
Linwang Gan, MD
Department of Nephrology
the Affiliated Hospital of Southwest Medical University
No. 25 Taiping Street
Luzhou 646000, Sichuan Province, China
Email: [email protected]
Original
Intraperitoneal vancomycin plus levofloxacin for the treatment of peritoneal dialysis-related peritonitis in patients with no response to cefazolin plus ceftazidime
Jiafan Zhou, Yajuan Huang, Xing Zhang, Liping Xiong, Rui Zhang, and Hongrui Shi
Price
42.00 $
Volume 101 (2024) p. 164 - 170
Abstract
Clinical Nephrology, Vol. 101 – No. 4/2024 (164-170)
Intraperitoneal vancomycin plus levofloxacin for the treatment of peritoneal dialysis-related peritonitis in patients with no response to cefazolin plus ceftazidime
Jiafan Zhou*, Yajuan Huang*, Xing Zhang, Liping Xiong, Rui Zhang, and Hongrui Shi
Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Introduction: Peritoneal dialysis-related peritonitis (PDRP) should be treated as soon as possible by an empirical regimen without waiting for effluent bacterial culture results. We retrospectively investigated patients treated with vancomycin plus levofloxacin as a treatment regimen if there was no response to cefazolin plus ceftazidime.
Materials and methods: We collected records of adult patients with PDRP from January 1, 2013, to November 30, 2020. The characteristics of episodes of PDRP with no response to cefazolin plus ceftazidime treated by intraperitoneal (IP) injection of vancomycin plus levofloxacin were analyzed.
Results: 118 episodes of PDRP were recorded, among which 115 episodes were treated with IP antibiotics. 93 episodes were treated with cefazolin plus ceftazidime. In 38 episodes, treatment was switched to IP injection of vancomycin plus levofloxacin if there was no response to cefazolin plus ceftazidime. 26/38 (68.4%) episodes were cured by vancomycin plus levofloxacin. Fever, diabetes, fasting glucose, a decrease in effluent leukocytes on day 3 and day 5, and Charlson Comorbidity Index (CCI) scores were significantly different between uncured and cured episodes. No variable was associated with treatment failure after multiple logistic regression. Fever, diabetes, a decrease in effluent leukocytes on day 3, and CCI score were associated with treatment failure after univariable logistic regression.
Conclusion: Vancomycin plus levofloxacin may be effective if patients are not responsive to cefazolin plus ceftazidime.
*Jiafan Zhou and Yajuan Huang contributed equally to this work.Correspondence to:
Hongrui Shi, MD
or
Rui Zhang, MD, PhD
Department of Nephrology
the Sixth Affiliated Hospital
Sun Yat-sen University
No. 26, Yuancun Erheng Road
Guangzhou, Guangdong, 510655, China
Email: [email protected]; [email protected]
Original
Cost-utility analysis of pembrolizumab versus nivolumab in the treatment of metastatic colorectal cancer from the perspective of the healthcare payer
Zhen Lu, Xiaoyan Huang, Yingjuan Ou, Qinbo Wang, and Qirong Tan
Price
42.00 $
Volume 63 (2025) p. 179 - 189
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 63 – No. 5/2025 (179-189)
Cost-utility analysis of pembrolizumab versus nivolumab in the treatment of metastatic colorectal cancer from the perspective of the healthcare payer
Zhen Lu1, Xiaoyan Huang2#5, Yingjuan Ou2#4#5, Qinbo Wang2#4#5, and Qirong Tan3
1Department of Pharmacy, JianLi People’s Hospital, Jingzhou, 2Department of Pharmacy, The sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 3Department of General Practice, the University of HongKong-Shenzhen Hospital, Shenzhen, 4Department of Graceland Medical Center, The Sixth Affiliated Hospital, Sun Yat-Sen, University, Guangzhou, and 5Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Background: Colorectal cancer (CRC) is a malignant tumor with the third highest incidence worldwide. The comprehensive economic evaluation of programmed cell death protein-1 inhibitors in China, however, has not yet been carried out. The aim of this study is to assess the cost-utility of pembrolizumab and nivolumab in the treatment of metastatic colorectal cancer (mCRC).
Materials and methods: A Markov model microsimulation of efficacy and cost-utility analysis (CUA) was carried out, and efficacy and safety data were compared using network meta-analysis. Literature screening and data extraction were performed according to established criteria where the main outcome indicators, complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were compared between two treatments. The lifetime cost and outcomes of mCRC treatment were estimated, and quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) were used to evaluate the economy of each program.
Results: A total of 442 studies were evaluated of which 15, with a total of 798 patients, were included in the analysis. Of these, 13 evaluated PD, and total patients for CR, PR, SD, and PD were 82, 283, 160, and 180 respectively. The corresponding heterogeneity values were (p = 0.13, heterogeneity index as percentage (I2) = 29.53%), (p < 0.01, I2 = 72.55%), (p = 0.03, I2 = 46.54%), (p < 0.01, I2 = 80.31%), and (p = 0.13 > 0.05). The proportion of patients classified as CR in the pembrolizumab group was greater than in the nivolumab group (0.105 vs. 0.085). However, the number of patients classified as PR and SD in the nivolumab group exceeded those in the pembrolizumab group. The number of patients classified as PD were similar in the two groups. Combination therapy nivolumab + ipilimumab yielded an incremental gain of 0.04 QALYs at an additional cost of 356,723 ¥. The ICER reached 8,918,075 ¥/QALYs, surpassing three times the per capita gross domestic product (GDP).
Conclusion: Both pembrolizumab and nivolumab showed beneficial effects in patients with mCRC. Nivolumab in combination with ipilimumab led to improved progression-free survival, but the values for ICER reached 8,918,075 ¥/QALYs. Treatment of non-resectable or metastatic microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) advanced solid tumors CRC with pembrolizumab alone, in the Chinese population examined, was the most cost-effective, where the willingness-to-pay threshold was 242,928 ¥/QALY (100 ¥ = 13.75 US$ and 12.63 €).Correspondence to:
Qinbo Wang, MD
Department of Pharmacy
the Sixth Affiliated Hospital
Sun Yat-Sen University
26# Erheng Road, Yuan Village, Tianhe District
Guangzhou 510655, China
or
Qirong Tan, MD
Department of General Practice
the University of HongKong-Shenzhen Hospital
No.1 Haiyuan 1st Road, Futian District
Shenzhen, 518053, China
Email: [email protected]; [email protected]
Original
Network meta-analysis of bisphosphonates in the treatment of bone metastases from breast cancer
Li-Wen Zhang, An Huang, Hong-Fang Ma, and Jun Shen
Price
42.00 $
Volume 64 (2026) p. 470 - 481
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 64 – No. 9/2026 (470-481)
Network meta-analysis of bisphosphonates in the treatment of bone metastases from breast cancer
Li-Wen Zhang1*, An Huang2*, Hong-Fang Ma3, and Jun Shen1
1Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou City, 2Department of Breast Surgery, Maternal and Child Health Hospital, Yiwu City, and 3Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
Objective: Through a network meta-analysis, this study aimed to systematically evaluate the efficacy and safety of bisphosphonates in reducing skeletal-related events in patients with bone metastases from breast cancer, providing clinical guidance for treatment selection.
Materials and methods: Randomized controlled trials (RCTs) on bisphosphonate therapy for bone metastases in breast cancer were retrieved from PubMed, Cochrane, and Embase databases from inception to January 2025. Statistical analyses were performed using Stata software.
Results: 22 studies involving 14,934 patients were included. The bisphosphonates evaluated were pamidronate, zoledronate, clodronate, and ibandronate. Regarding the reduction of pathological fractures, the efficacy ranking was clodronate > ibandronate > pamidronate > zoledronate. Significant differences were found between clodronate and pamidronate (OR = –1.41, 95% CI: –2.78 to –0.04) and between clodronate and zoledronate (OR = –1.44, 95% CI: –2.85 to –0.04). For hypercalcemia reduction, zoledronate was more effective than clodronate and pamidronate, though differences were not statistically significant (p > 0.05). In terms of safety, ibandronate showed fewer adverse reactions than clodronate and zoledronate, with a significant difference between ibandronate and zoledronate (OR = –1.14, 95% CI: –1.99 to –0.28).
Conclusion: Clodronate was most effective in reducing pathological fractures, zoledronate was superior in controlling hypercalcemia, and ibandronate demonstrated the best safety profile. Further clinical studies are warranted to clarify the comparative advantages of each bisphosphonate and support individualized treatment decisions.
*Both authors contributed equally to this study.Correspondence to:
Jun Shen, MD
Department of Surgical Oncology
Sir Run Run Shaw Hospital
Zhejiang University School of Medicine
No. 3. East road of Qingchun
Hangzhou 310016, Zhejiang Province, China
Email: [email protected]
