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Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 2/2014 (151-158)

Pharmacokinetics of simvastatin lactone and its active metabolite simvastatin hydroxy acid in healthy Chinese male and female volunteers

Weihong Yang¹,², Hongpong Xu³, Yanliang Song¹, Xiaofei Wang¹, Xinwei Ren¹, Dengzhi Zhao¹, Yaoxin Cai¹, Shengjun Zhang⁴, Jianmin Huang⁴, Li-Rong Zhang¹, Tianyi Zhang⁵, and Ming Zuo⁵

¹Department of Pharmacology, School of Basic Medical Sciences, ²Department of Forensic Medicine, School of Basic Medical Sciences, Zhengzhou University, ³Zhengzhou Railway Vocational-Technical College, ⁴The First Affiliated Hospital of Zhengzhou University, Zhengzhou, and ⁵Frontage Laboratories (Shanghai) Co., Ltd, Shanghai, China
Background: Gender differences in pharmacokinetics have been reported to have important clinical consequences; however, no information about differences in the pharmacokinetics of the cholesterol-lowering drug simvastatin lactone and its metabolite, simvastatin hydroxy acid, in males and females is available. Objective: The aim of this study was to investigate the effect of gender on the pharmacokinetics of simvastatin lactone and simvastatin hydroxy acid in healthy Han Chinese volunteers. Methods: 16 healthy volunteers (8 males and 8 females) were orally administered a single dose of 40 mg simvastatin lactone after an overnight fast. Plasma was then collected 24 hours after simvastatin lactone administration. Concentrations of simvastatin lactone and simvastatin hydroxy acid were measured by high performance liquid chromatography/mass spectrometry/mass spectrometry (HPLC/MS/MS). Results: There were no significant associations between the pharmacokinetic parameters of simvastatin lactone and gender. For simvastatin hydroxy acid, peak plasma concentrations (C_max) and dose-normalized by the subject weight C_max (NC_max) were higher in females than in males. Furthermore, NC_max and dose-normalized by the subject weight AUC (NAUC_0–24h, NAUC_0–∞) ratios of simvastatin hydroxy acid to simvastatin lactone in females were higher than in males. Conclusion: This study indicates that gender affects the plasma concentrations of active simvastatin hydroxy acid, but has no significant effect on parent simvastatin lactone. Raised plasma concentrations of simvastatin hydroxy acid in females may enhance the risk of systemic adverse effects during simvastatin lactone treatment.Correspondence to:
Prof. Li-Rong Zhang, MD
Department of Pharmacology, School of Medicine
Zhengzhou University
100 Science Road, Zhengzhou 450001, China
Email: [email protected]

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 9/2015 (737-745)

Effect of CYP3A4*1G, CYP3A5*3, POR*28, and ABCB1 C3435T on the pharmacokinetics of nifedipine in healthy Chinese volunteers

Xiao-Fei Wang¹,²*, Liang Yan²*, Hui-Min Cao², Lu-Man Wei², Wei-Hong Yang², Sheng-Jun Zhang³, and Li-Rong Zhang²

¹Translational Medicine Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, ²Department of Pharmacology, School of Basic Medical Sciences, and ³Clinical Research Center, First Affiliated Hospital, Zhengzhou University, Zhengzhou, China
Objective: Nifedipine is a calcium channel blocker that is widely used in the treatment of cardiovascular disease. However, significant individual variances in the disposition of nifedipine have been reported, and genetic factors are considered to play an important role. The aim of the present study was to investigate the effect of CYP3A4*1G, CYP3A5*3, ABCB1-C3435T, and POR*28 genetic polymorphisms on nifedipine pharmacokinetics in healthy Chinese volunteers. Methods: 45 healthy Chinese volunteers enrolled in this study received a single oral dose of 90 mg nifedipine after providing written informed consent. Volunteers were genotyped for CYP3A4*1G, CYP3A5*3, POR*28, and ABCB1-C3435T. The blood concentrations of nifedipine were determined by high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Results and discussion: There were significant differences of AUC_0–∞ and AUC_0–48h in the different CYP3A5*3 genotype groups (p = 0.043 and p = 0.048, respectively). The CYP3A5*3 GG group and POR*28 CT/TT group were found to have lower AUC_0–∞ and C_max compared with the POR*28 CC group (p = 0.046 and p = 0.002, respectively). In addition, the POR*28 CT/TT group was found to have longer t_1/2 but lower C_max than the CYP3A4*1G GG group (p = 0.032 and p = 0.002, respectively) as well as the CYP3A4*1G GG and the CYP3A5*3 GG group (p = 0.038 and p = 0.036, respectively) compared with the POR*28 CC group. No significant associations were found between CYP3A4*1G/ABCB1-C3435T polymorphism and pharmacokinetics of nifedipine. Conclusion: Both CYP3A5*3 and POR*28 polymorphisms are found to be associated with the difference in disposition of nifedipine; POR*28 is considered to have an impact on CYP3A4 activity.Correspondence to:
Prof. Li-Rong Zhang, PhD
Department of Pharmacology, School of Medicine
Zhengzhou University
100 Science Road, Zhengzhou 450001, China
Email: [email protected] and [email protected]

Abstract

Clinical Nephrology, Vol. 84 – No. 2/2015 (95-99)

Effect of BMP7 on podocyte transdifferentiation and Smad7 expression induced by hyperglycemia

Liqiu Liu, Wen Fu, Jing Xu, Leping Shao, and Yanfei Wang

Department of Nephrology, the Affiliated Hospital of Qingdao University, Qingdao, China
Objective: To investigate the effect of BMP7 on the transdifferentiation and Smad7 expression of podocytes induced by high glucose in vitro and to explore its possible protective mechanisms. Methods: Mouse podocytes were cultured and divided into normal glucose group (NG), high glucose group (HG), mannitol group, NG+BMP7 group, and HG+BMP7 group. Real-time PCR and Western blot were applied respectively to detect the mRNA and protein expression levels of synaptopodin, desmin, and Smad7. Results: The cells significantly up-regulated the mRNA and protein expression of desmin and reduced the expression of both synaptopodin and Smad7 after 48 hours (vs. NG, p < 0.01). BMP7 dramatically suppressed the mRNA and protein expression of desmin and protected the expression of synaptopodin and Smad7 after incubation with high glucose for 48 hours (vs. HG, p < 0.01). Conclusions: BMP7 can inhibit the epithelial-to-mesenchymal cell transformation (EMT) of podocytes induced by high glucose; Smad7 may mediate the blunting effects of BMP7 on high glucose in podocytes.Correspondence to:
Liqiu Liu
Department of Nephrology
The Affiliated Hospital of Qingdao University
Qingdao 266003, China
Email: [email protected]

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 3/2016 (193-199)

Effects of UGT1A1*6, UGT1A1*28, and ABCB1-3435C>T polymorphisms on irinotecaninduced toxicity in Chinese cancer patients

Liang Yan¹*, Xiao-fei Wang²*, Lu-man Wei¹, Ya-li Nie¹, Jing-yang Liu¹, and Li-rong Zhang¹

¹Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, and ²Translational Medicine Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China
Object: The aim of this study was to investigate whether UGT1A1*6/*28 or ABCB1-3435C>T polymorphisms affect irinotecan-induced severe diarrhea and neutropenia in Chinese cancer patients. Methods: A total of 157 cancer patients was enrolled in this study and the genotypes of UGT1A1*6/*28 and ABCB1-3435C>T polymorphisms were analyzed by PCRSanger sequence. The relationship between UGT1A1*6/*28 and ABCB1-3435C>T polymorphisms and irinotecan induced severe diarrhea and neutropenia were analyzed. Results and conclusion: UGT1A1*6 and UGT1A1*28 polymorphisms were associated with severe neutropenia (p = 0.025, p = 0.022, respectively) but not diarrhea (p = 0.343, p = 0.185, respectively), and ABCB1- 3435C>T polymorphism was not associated with irinotecan induced severe toxicities (p = 0.457, p = 0.161, respectively).Correspondence to:
Prof. Li-rong Zhang, MD
Department of Pharmacology
School of Basic Medical Sciences
Zhengzhou University
100 Science Road, Zhengzhou 450001, China
Email: [email protected]

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 6/2016 (450-454)

Prevalence of overweight in schizophrenia patients in Asia: findings of the research on Asian psychotropic prescription patterns (REAP) study

Fei Wang¹, Yu-Tao Xiang¹, Gabor S. Ungvari²,³, Chee H. Ng⁴, Helen F.K. Chiu⁵, Wei Zheng⁶, Chay-Hoon Tan⁷, and Naotaka Shinfuku⁸

¹Unit of Psychiatry, Faculty of Health Sciences, University of Macau, Macao SAR, China, ²School of Psychiatry & Clinical Neurosciences, University of Western Australia, ³University of Notre Dame Australia/Marian Center, Perth, ⁴Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia, ⁵Department of Psychiatry, Chinese University of Hong Kong, Hong Kong SAR, ⁶Guangzhou Brain Hospital (Guangzhou Huiai Hospital), Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China, ⁷Department of Pharmacology, National University of Singapore, Singapore, and ⁸International Center for Medical Research, Kobe University School of Medicine, Kobe, Japan
Objective: This study examined the proportion of overweight in schizophrenia inpatients in selected Asian countries and territories and its independent demographic and clinical correlates. Method: Data on 1,534 hospitalized schizophrenia patients in 9 Asian countries and territories were collected by a review of medical files supplemented by a clinical interview during a 1-month period. Patients’ sociodemographic and clinical characteristics, prescriptions of psychotropic drugs, and Body Mass Index (BMI) were recorded using a standardized protocol and data collection procedure. For analyzes, BMI ≥ 25 kg/m² was defined as overweight. Results: The proportion of overweight was 35.8% (549/1,534) in the entire sample, with 39.7% (224/564) in females and 33.5% (325/970) in males (p = 0.01) and with wide inter-country variations. Multiple logistic regression analysis revealed that after controlling for study sites, overweight was independently associated with more frequent use of mood stabilizers (p < 0.001, odds ration (OR) = 1.4, 95% confidence interval (CI) = 1.1 – 1.8) and longer length of illness (p < 0.001, OR = 1.6, 95% CI = 1.2 – 2.1) but was less likely found in male patients (p = 0.003, OR = 0.7, 95% CI = 0.5 – 0.8). Conclusions: The prevalence of overweight Asian schizophrenia patients is significantly lower than the reported figures among their Western counterparts. There is considerable variation in prevalence of overweight schizophrenia patients within Asian countries and territories.Correspondence to:
Dr. Yu-Tao Xiang, MD, PhD
3/F, Building E12, Faculty of Health Sciences
University of Macau
Avenida da Universidade, Taipa, Macau SAR, China
Email: [email protected]

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 58 – No. 6/2020 (299-309)

Potentially inappropriate medications at admission and discharge in older adults: A comparison of the Beers 2019 and 2015 criteria 

Feifei Wang¹*, Zhuo Ma³*, Meng Liu², and Xinan Wu¹

¹Pharmacy Department of Hefei BOE Hospital, Hefei, ²Pharmacy Department of Lu’an Second People’s Hospital, Lu’an, and ³Pharmacy Department of Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
Background: Potentially inappropriate medications (PIMs) for older adults are those with an unfavorable risk-beneﬁt ratio when more effective and safe therapeutic alternatives are available. PIMs represent an important public health problem.
Aim: The study aimed to investigate the prevalence of PIM at admission and discharge identified by the Beers 2019 and 2015 criteria in older patients in China and to identify the correlates of PIMs.
Materials and methods: This was a cross-sectional study conducted in a tertiary hospital in China. Hospitalized patients in the internal medicine department aged ≥ 60 years were enrolled from June 2018 to October 2018. Information on medications at admission and discharge was collected and evaluated regarding PIMs using Beers 2019 and 2015 criteria. The concordance between PIM use according to Beers 2019 and 2015 criteria was calculated using κ tests. Multivariate logistic regressions were used to evaluate the factors associated with PIM use.
Results: Totally, 604 patients aged ≥ 60 years were included. The prevalence of PIM at admission was 53.3 and 55.0% according to the Beers 2015 and 2019 criteria, whereas the prevalence of PIM at discharge was 32.0 and 33.4% according to both criteria. The most frequent PIMs at admission and discharge were both diuretics according to the Beers 2019 criteria. PIMs at admission and discharge identified by the Beers 2019 criteria were both associated with the number of prescribed medications, acute heart failure, and chronic heart failure.
Conclusion: The Beers 2019 and 2015 criteria showed good accordance in our study.

*These authors contributed equally to this work.Correspondence to:
 Xinan Wu, PhD 
Pharmacy Department of Hefei BOE Hospital
Intersection of Dongfang Avenue and Wenzhong Road
Xinzhan District, Hefei 230000, China
Email: [email protected]

Abstract

Clinical Neuropathology, Vol. 43 – No. 5/2024 (147-156)

Application of carbonic anhydrase IX in sporadic hemangioblastoma of the central nervous system and hemangioblastoma associated with von Hippel–Lindau disease

Xue Chen¹#, Xiaoxiang Gao²#, Jiaqi Bo¹#, Haixia Bi³, Haoyang Zhang¹, Yuting Liu¹, Jie Yu¹, Xianghua Yi¹, Fei Wang⁴, Suxia Zhang¹, and Yu Zeng¹

¹Department of Pathology, Tongji Hospital, School of Medicine, Tongji University, ²Department of Orthopedics, Naval Medical Research Institute, Chinese People‘s Liberation Army Naval Medical Center, ³Department of Pathology, Shibei Hospital, Jing’an District, and ⁴Department of Neurosurgery, Tongji Hospital, School of Medicine, Tongji University School of Medicine, Shanghai, China
Objective: This research aims to examine the expression of carbonic anhydrase IX (CAIX) protein in hemangioblastoma of the central nervous system and its potential application in pathological diagnosis and differential diagnosis.
Materials and methods: Immunohistochemistry was used to identify the expression of CAIX and the α-inhibin protein. The sensitivity and specificity of CAIX and α-inhibin for identifying hemangioblastoma of the central nervous system were compared. In addition, 86 patients with meningiomas were gathered to detect CAIX protein expression. Hemangioblastoma and angiomatous, microcystic the two subtypes of meningiomas, were compared for CAIX and EMA protein expression.
Results: In hemangioblastoma, there were significant differences in the median positive percentage and staining intensity of CAIX and α-inhibin (p < 0.05). There was no discernible difference in the expression of the CAIX protein between sporadic hemangioblastoma of the central nervous system and those linked to von Hippel‒Lindau disease. In comparison to angiomatous and microcystic meningiomas, the positive rate of CAIX in hemangioblastomas was substantially greater (p < 0.001). The expression of EMA in microcystic meningioma (6/6) and angiomatous meningioma (17/17) was significantly different from hemangioblastoma (0/30) (p < 0.0001).
Conclusion: Hemangioblastoma might be diagnosed with high specificity and sensitivity through CAIX immunohistochemistry. The combination of CAIX with EMA is useful for the diagnosis and differential diagnosis of hemangioblastoma.

#These authors have contributed equally to this work and share the first authorship.Correspondence to:
Yu Zeng, MD, PhD, Associate Professor
Department of Pathology
or
Suxia Zhang, MM
Department of Pathology
or
Fei Wang, MD
Department of Neurosurgery, Tongji Hospital, School of Medicine, Tongji University
389, Xincun Road
Ptuo District, Shanghai 200065, China
Email: [email protected] ; [email protected]; [email protected]

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 64 – No. 5/2026 (231-241)

Epidemiological characteristics of severe skin adverse reactions caused by immune checkpoint inhibitors based on case reports 

Su-na Tang¹#², Xiao-wen Ma², Xiao-yan Zhang², Na-na Zhang², Fei Wang², Feng-lin Ye¹, Na-na Chen¹, Ping Yang¹, and Ning-ning Zhu²

¹Department of Thoracic Surgery, First Affiliated Hospital of Bengbu Medical University, and ²School of Nursing, Bengbu Medical University, Bengbu, Anhui, China
Objective: To investigate the epidemiological characteristics of severe cutaneous adverse reactions (cirAEs) induced by immune checkpoint inhibitors (ICIs) and to provide evidence for the rational clinical use of ICIs and pharmacovigilance for cutaneous toxicities.
Materials and methods: We systematically searched the PubMed, MEDLINE, EMBASE, CNKI, and Wanfang databases using keywords including “immune checkpoint inhibitors,” “cutaneous adverse reactions,” “cutaneous toxicity,” “induced,” and “case,” and their combinations to identify detailed case reports on cirAEs. Data on patient demographics (sex and age), primary cancer type, ICI use, time to cirAE onset, cirAE severity grading, and reaction classification were extracted. Descriptive statistics, co-occurrence analysis of clinical manifestations, and the Apriori algorithm were employed to analyze cirAE patterns.
Results: The analysis included a total of 120 articles involving 126 patients (male: 80; female: 46) with a mean age of 63.05 ± 11.85 years. The highest incidence was observed in patients aged 60 – 69 years. The primary cancers were predominantly non-small cell lung cancer and melanoma. Programmed death 1 (PD-1) inhibitors were the most commonly used therapeutic agents. The median time to onset was 15 – 28 days. Most cases were classified as severe Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).
Conclusion: Healthcare professionals must remain vigilant for severe cirAEs and ensure timely diagnosis and management to safeguard patient safety during ICI therapy.Correspondence to:
Prof. Ningning Zhu
School of Nursing
Bengbu Medical University
Bengbu 233030, Anhui, China
Email: [email protected]

Abstract

Li Zheng¹,², Liaoyun Zhang¹, Fei Wang¹, Yongxian Jiang¹, Fei Lv², and Gen Li¹

¹Pharmacy Department, Sichuan Provincial Women’s and Children’s Hospital/The Affiliated Women’s and Children’s Hospital of Chengdu Medical College, and ²Pharmacy Department, Public Health Clinical Center of Chengdu, Chengdu, China
Antidepressant overdose is a prevalent method of self-harm in patients with depression including bipolar disorder. According to the published literature, typical adverse effects are seizures, prolonged QT intervals, and arrhythmias, with cardiotoxicity primarily observed in adults. This paper reports the first documented case of an 11-year-old adolescent with depression who ingested a massive overdose comprising sertraline (60 tablets at 50 mg, giving a total dose of 3 g), quetiapine fumarate (50 tablets at 100 mg giving a total dose of 5 g) and lamotrigine (120 tablets at 25 mg giving a total dose of 3 g). At ~ 4 hours post ingestion, the patient developed hypoxemia, hypotension, persistent seizures, resulting in cardiac arrest. This case report offers critical insights into the clinical management of such cases involving pediatric populations. Correspondence to:
Fei Lv, MD, Pharmacy Department ,Public Health Clinical Center of Chengdu, Chengdu, China, Gen Li, MD, Pharmacy Department, Sichuan Provincial Women’s and Children’s Hospital/The Affiliated Women’s and Children’s Hospital of Chengdu Medical College, Chengdu, China
Email: [email protected]

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