Volume 55 (2017), No. 6/2017(June)
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Editorial
Benzodiazepine prescribing in the elderly
Barry G. Woodcock
Page No. 465
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 6/2017 (465)
Benzodiazepine prescribing in the elderly
Barry G. Woodcock
Original
Patterns of benzodiazepine prescribing by neuropsychiatrists and general practitioners for elderly patients in Germany in 2014
Thomas Mell, Louis Jacob, Ida Fuhr, Sandra Dick, Michael Rapp, Karel Kostev
Price
42.00 $
Page No. 466
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 6/2017 (466-471)
Patterns of benzodiazepine prescribing by neuropsychiatrists and general practitioners for elderly patients in Germany in 2014
Thomas Mell1, Louis Jacob2, Ida Fuhr1, Sandra Dick1, Michael Rapp3, Karel Kostev4
1Department of Psychiatry and Psychotherapy, Charité – University Medicine Berlin, Berlin, Germany, 2Faculty of Medicine, University of Paris 5, Paris, France, 3Department of Social and Preventive Medicine, University of Potsdam, Potsdam, and 4IMS Health, Epidemiology, Frankfurt, Germany
Background: The patterns of benzodiazepine prescriptions in older adults are of general and scientific interest as they are not yet well understood. The aim of this study was to compare the prescription patterns of benzodiazepines in elderly people in Germany to determine the share or proportion treated by general practitioners (GP) and neuropsychiatrists (NP). Methods: This study included 31,268 and 6,603 patients between the ages of 65 and 100 with at least one benzodiazepine prescription in 2014 from GP and NP, respectively. Demographic data included age, gender, and type of health insurance coverage. The share of elderly people with benzodiazepine prescriptions was estimated in different age and disease groups for both GP and NP patients. The share of the six most commonly prescribed drugs was also calculated for each type of practice. Results: The share of people taking benzodiazepines prescribed by GP increased from 3.2% in patients aged between 65 and 69 years to 8.6% in patients aged between 90 and 100 years, whereas this share increased from 5.4% to 7.1% in those seen by NP. Benzodiazepines were frequently used by patients suffering from sleep disorders (GP: 33.9%; NP: 5.5%), depression (GP: 17.9%; NP: 29.8%), and anxiety disorders (GP: 14.5%; NP: 22.8%). Lorazepam (30.3%), oxazepam (24.7%), and bromazepam (24.3%) were the three most commonly prescribed drugs for GP patients. In contrast, lorazepam (60.4%), diazepam (14.8%), and oxazepam (11.2%) were those more frequently prescribed to NP patients. Conclusion: Prescription patterns of benzodiazepine in the elderly varied widely between GP and NP.
Correspondence to:
Prof. Dr. Karel Kostev
IMS Health, Epidemiology
Darmstädter Landstraße 1089
60598 Frankfurt am Main, Germany
Email: [email protected]
Original
Real-world prescribing patterns of long-acting benzodiazepines for elderly Koreans in 2013
So Yun Park, SeungJin Bae, Ju-Young Shin
Price
42.00 $
Page No. 472
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 6/2017 (472-479)
Real-world prescribing patterns of long-acting benzodiazepines for elderly Koreans in 2013
So Yun Park1, SeungJin Bae1, Ju-Young Shin2
1College of Pharmacy, Ewha Womans University, Seoul, and 2School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
Objective: We aimed to estimate the prevalence of prescriptions to long-acting benzodiazepines (BZDs) among elderly outpatients in Korea in 2013 and analyze the factors that led to inappropriate prescription practices. Methods: Using the Korea Health Insurance Review and Assessment Service-National Patients Sample database in 2013, we estimated the pattern of BZD prescription among elderly outpatients. BZDs were categorized as long-acting (half-life (T1/2) ≥ 20 hours) or short-acting (T1/2 < 20 hours). In addition, we investigated the pattern of BZD prescription for populations defined according to patient, healthcare provider, and geographic characteristics. Multivariate logistic regression analysis was performed to estimate odds ratios and 95% confidence intervals and identify predictors of long-acting BZD use. Results: Overall, 58,056 elderly patients (38,910 females, 67%) received at least 1 BZD prescription. The total number of BZD prescriptions was 78,843, of which long-acting BZD prescriptions accounted for 44.7%. Diazepam was the most frequently prescribed BZD (39.7%). Long-acting BZDs were most frequently prescribed in the primary-care setting and were relatively frequently prescribed in rural areas. Of the patients prescribed long-acting BZDs, 435 (3.5%) had chronic obstructive pulmonary disease. Long-acting BZD use varied across different medical institutions (p < 0.05). Conclusions: A decrease in long-acting BZD use was identified relative to data from previous studies. However, BZDs continued to be used, and their use should be further limited in the primary-care setting and in rural areas. The results of this study may provide fundamental data for further review of BZD utilization.
Correspondence to:
SeungJin Bae
Associate Professor
College of Pharmacy, Ewha Womans University
52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, South Korea
or
Ju-Young Shin
Assistant Professor, School of Pharmacy,
Sungkyunkwan University
2066 Seobu-ro, Jangan-gu,
Suwon, Gyeong gi-do, South Korea
Email: [email protected] or [email protected]
Original
Benzodiazepine prescribing in the elderly in Germany and Korea: A comparison of two observational studies
Barry Woodcock, Karel Kostev, Ju-Young Shin
Price
42.00 $
Page No. 480
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 6/2017 (480-482)
Benzodiazepine prescribing in the elderly in Germany and Korea: A comparison of two observational studies
Barry Woodcock1, Karel Kostev2, Ju-Young Shin3
1Dustri Medical Science Publications, Rockledge, FL, USA,
2IMS Health, Epidemiology, Frankfurt, Germany, and
3School of Pharmacy, Sungkyunkwan University, Suwon, Korea
Objectives: To identify differences and similarities in benzodiazepine (BZD) prescribing patterns in elderly patients reported in two separate and independent investigations, one from Germany for the year 2014 and the other from Korea for the year 2013. Methods: Data on patients over 65 years, who were prescribed at least one BZD, were obtained from population databases. The design and characteristics of the two studies were similar. Results: The use of BZDs in the elderly in Korea was several-fold higher than in Germany depending on the age stratification. Sleep disorders and depression were less common indications for BZDs in Korea. The use of long-acting BZDs in both countries was higher in patients attending general practitioners compared to specialized hospital departments and clinics. In Korea, diazepam was the most commonly used BZD in general practice. In Germany, lorazepam was the most commonly used BZD both in general practice and neuropsychiatric clinics. Conclusions: The results of this comparison show that a reduction in the use of BZDs in the elderly in Korea may be possible and that in Germany, in some instances, these drugs may be under-used in this patient group. This cross-national comparison may help to reduce inappropriate use of BZD medication and improve prescribing in the elderly but this would have to be the subjects of a more detailed analysis.
Correspondence to:
Prof. Barry G. Woodcock, PO 20 02 32, 63308 Rödermark, Germany
Email: woodcock@
clinpharmacol.com
Original
A meta-analysis of the effect of CYP2D6 polymorphism on the pharmacokinetics and pharmacodynamics of metoprolol
Shuchun Li, Han Lin, WenHuan Sun, YingLi Wang, YouFang Ding, HuanHu Zhao, ShangJian Liu
Price
42.00 $
Page No. 483
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 6/2017 (483-492)
A meta-analysis of the effect of CYP2D6 polymorphism on the pharmacokinetics and pharmacodynamics of metoprolol
Shuchun Li1, Han Lin1, WenHuan Sun1, YingLi Wang1, YouFang Ding1, HuanHu Zhao1, ShangJian Liu2
1Institute of Chinese Minority Traditional Medicine, MinZu University of China and 2DongZhiMen Hospital, Beijing University of Chinese Medicine, Beijing, China
Objective: To conduct a meta-analysis on the effect of CYP2D6 polymorphism on the pharmacokinetics and pharmacodynamics of metoprolol. Methods: A systematic review and meta-analysis of studies on the effect of CYP2D6 polymorphism on metoprolol pharmacokinetics and pharmacodynamics was performed by using the China national knowledge infrastructure (CNKI), database for Chinese technical periodicals (VIP), Wanfang, and PubMed databases up to the end of January 2015. Review Manager 5.3 (the coherence collaboration, www.gradepro.org) and comprehensive Meta-Analysis Software v2 (CMA) Biostat, Englewood, NJ, USA) were used for meta-analysis. Results: A total of 567 cases from 7 studies were included in the present study. Meta-analysis results showed that the area under the curve (AUC)0–∞ (RR = –6.75, 95% CI (–9.18, –4.31), p < 0.00001); Cmax (RR = –2.40, 95% CI (–3.25, –1.54), p < 0.00001); T1⁄2 (RR = –4.81, 95% CI (–6.86, –2.76), p < 0.00001); CL/F (RR = 1.60, 95% CI (1.03,2.17), p < 0.00001); heart rate (RR = 1.48, 95% CI (0.03, 2.92), p = 0.05), systolic blood pressure (RR = –0.69, 95% CI (–1.85,0.47), p = 0.24); and diastolic blood pressure (RR = –1.95, 95% CI (–3.14, –0.76), p = 0.001). Begg’s funnel plot test showed that the pharmacokinetic parameters (AUC0–∞, Cmax, T1⁄2, and CL/F) and pharmacodynamic parameters (HR, DBP, and SBP) were symmetric. Egger’s test showed that the pharmacokinetic parameters were asymmetrical, and its intercept was statistically significant (p < 0.05), which was indicative of publication bias. The pharmacodynamic parameter intercept was not statistically significant (p > 0.05), indicating that no publication bias existed. Conclusion: CYP2D6 polymorphism significantly influenced the pharmacokinetic parameters of metoprolol. It also affected heart rate and diastolic blood pressure, whereas systolic pressure was not affected.
Correspondence to:
ShangJian Liu, MD
DongZhiMen Hospital
Beijing University of Chinese Medicine
5 Hai Yun Cang, 100700 Beijing, China
Email: [email protected]
Original
Prevalence of aspirin resistance in patients with type II diabetes: a descriptive-analytical study
Rahimeh Eskandarian, Mohammadreza Razavi, Abolfazal Fattah, Kamran Ghods, and Mohammad Forozeshfard
Price
42.00 $
Page No. 493
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 6/2017 (493-497)
Prevalence of aspirin resistance in patients with type II diabetes: a descriptive-analytical study
Rahimeh Eskandarian1, Mohammadreza Razavi2, Abolfazal Fattah3, Kamran Ghods1, and Mohammad Forozeshfard4
1Department of Interventional Cardiology, 2Nursing Care Research Center, 3Department of medical, Faculty of Medicine, and 4Cancer Research Center and Department of Anesthesiology, Semnan University of Medical Sciences, Semnan, Iran
Background: Aspirin resistance is one of the most important factors for arterial thrombotic events in diabetic patients. This study aimed to evaluate aspirin resistance in diabetic patients. Methods: In this cross-sectional study, 180 patients who received 80 mg of aspirin daily for at least 10 days were studied, and their urinary 11-DH-TXB2 was measured. Those with 11-dehydro-thromboxane B2 above 1,500 pg/mg creatinine were considered aspirin resistant. Data with significance level of 5% were analyzed in SPSS-16. Results: The mean ± SD of patient age was 60.22 ± 9.59 years and 50% (n = 90) were male. BMI was normal in 29.4% of the patients (n = 53), the others were overweight or obese. Aspirin resistance was observed in 33 (18%) patients. The relationship between aspirin resistance and gender, age, and BMI was not significant (p > 0.05). Conclusions: There is a high prevalence of aspirin resistance in diabetic patients and given that such patients are at risk of arterial thrombotic events, evaluation of aspirin resistance is suggested for those at a high risk of cardiovascular events or recurring events despite the use of aspirin.
Correspondence to:
Mohammad Forozeshfard
Anesthesiologist
Cancer Research Center
Semnan University of Medical Sciences
Semnan, Iran
Email: [email protected]
Original
Overall survival in response to sorafenib with transarterial chemoembolization for BCLC stage B hepatocellular carcinoma: propensity score analysis
Yonghui Huang, Bin Chen, Ni Liu, Nan Li, Haitao Dao, Wei Chen, and Jianyong Yang
Price
42.00 $
Page No. 498
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 6/2017 (498-508)
Overall survival in response to sorafenib with transarterial chemoembolization for BCLC stage B hepatocellular carcinoma: propensity score analysis
Yonghui Huang, Bin Chen, Ni Liu, Nan Li, Haitao Dao, Wei Chen, and Jianyong Yang
Department of Interventional Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Objective: Barcelona clinic liver cancer (BCLC) stage B hepatocellular carcinoma (HCC) is a heterogeneous disease group. Transarterial chemoembolization (TACE) is indicated for BCLC stage B HCC, while sorafenib is indicated for BCLC stage C HCC. This study aimed to evaluate the efficacy of TACE+sorafenib compared with TACE monotherapy in the treatment of BCLC stage B HCC. Materials: Patients with BCLC stage B unresectable HCC. Methods: This was a retrospective study in patients with BCLC stage B HCC who received TACE (n = 144) or TACE+sorafenib (n = 46) between January 2008 and January 2014. Child-Pugh classification, history of hepatitis or cirrhosis, nodule number, tumor vascularity, ECOG performance status, adverse events, and survival were evaluated. Patients were matched 1 : 1 using the propensity score approach. Results: Median overall survival (OS) was 18.0 months in the TACE+sorafenib group compared with 10.0 months for TACE (p = 0.002). In matched patients, multivariate analysis showed that the use of TACE+sorafenib (HR = 0.351, 95%CI: 0.215-0.574, p < 0.001) and multiple-diffuse nodules (HR = 0.497, 95% CI: 0.293 – 0.884, p = 0.010) were independently associated with a better prognosis. Subgroup analysis showed survival benefits for patients with Child-Pugh A classification (p = 0.001), cirrhosis (p = 0.001), hepatitis B (p < 0.001), hypovascular lesion (p = 0.001), and both single/multiple nodules p = 0.001). Cumulative rates of adverse events were similar between the two groups (p = 0.155), but hand-foot syndrome (58.7% vs. 12.5%, p < 0.001) and diarrhea (60.9% vs. 40.3%, p = 0.02) were more frequent in the TACE+sorafenib group. Conclusions: The combination of TACE+sorafenib might improve the OS of patients with BCLC stage B HCC. These results also suggest that some subsets of patients could benefit more from the TACE+sorafenib combination.
Correspondence to:
Yonghui Huang, MD,
Department of Interventional Radiology
The First Affiliated Hospital, Sun Yat-sen University
Guangzhou 510080, China
Email: [email protected]
Original
Population pharmacokinetics of vancomycin in Chinese pediatric patients
Taotao Liu, Chen Deng, Daohai Cheng, Tianyan Zhou, Hua Lu, Wenxing Wei, Wei Lu
Price
42.00 $
Page No. 509
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 6/2017 (509-516)
Population pharmacokinetics of vancomycin in Chinese pediatric patients
Taotao Liu1, Chen Deng2,3, Daohai Cheng1, Tianyan Zhou2, Hua Lu1, Wenxing Wei1, Wei Lu2
1Department of Pharmacy, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 2State Key Laboratory of Nature and Biomimetic Drug, School of Pharmaceutical Sciences, Peking University, Beijing, and 3Pfizer (China) Research and Development Center, Shanghai, China
Objective: This study was conducted to develop a population pharmacokinetic (PopPK) model for vancomycin and to detect the significant covariates that influence the PopPKs to facilitate individualized therapy for Chinese pediatric patients. Methods: Patients ≤ 10 years old who received vancomycin for ≥ 72 hours between 2007 and 2010 were analyzed using a nonlinear mixed-effects modeling approach (NONMEM). A one-compartment model with first-order elimination was chosen to depict the data. Stepwise covariate modeling (SCM) was employed to detect significant covariates and obtain a final model. Internal validation methods, including bootstrapping and visual predictive checks (VPC), were applied to evaluate the robustness and predictive power of the final model. Results: The analysis included 54 pediatric inpatients with 128 serum concentration samples. The mean age (range) was 124.30 (1.29 – 541.4) weeks, the mean weight was 10.36 (1.4 – 33.5) kg, and the mean baseline serum creatinine (Scr) level was 0.39 (0.15 – 1.32) mg/dL. Pneumonia was the most common indication for vancomycin therapy (33.33%), followed by bacteremia (25.93%), and meningitis (22.22%). A PopPK model of vancomycin in Chinese pediatric patients was developed. Postnatal age (PNA) significantly affected the vancomycin clearance (CL) of pediatric patients, and the influence was described using the sigmoid maximum effect (Emax) model. The effect of body weight (WT) on CL and volume of distribution (V) was investigated using an allometric scaling equation. The final model parameters were CL(L/h) = 11.75×[PNA0.4672/(PNA0.4672+33.30.4672)]×(WT/70)0.75×e0.362 and V(L) = 54.49×WT/70×e0.6711. The model evaluation results suggested robustness and good predictability of the final model. Conclusion: A PopPK model of vancomycin for Chinese pediatric patients was developed in this study. The significant covariates distinguished in the final model can provide helpful information to facilitate individualized therapy for Chinese pediatric patients.
Correspondence to:
Taotao Liu, MSc
Department of Pharmacy
The First Affiliated Hospital of Guangxi Medical University
6 Shuangyong Road, Nanning, Guangxi, 530021 China
Email: [email protected]
Short
Report
“Total evidence” network meta-analysis as a tool for improving the assessment of biosimilars: application to etanercept in rheumatoid arthritis
Andrea Messori, Sabrina Trippoli, and Claudio Marinai
Price
42.00 $
Page No. 517
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 6/2017 (517-520)
“Total evidence” network meta-analysis as a tool for improving the assessment of biosimilars: application to etanercept in rheumatoid arthritis
Andrea Messori, Sabrina Trippoli, and Claudio Marinai
HTA Unit, ESTAR Toscana, Regional Health Service, Firenze, Italy
Since biosimilars generally have undergone less clinical research than originators, their place in therapy can be strengthened by increasing the amount of clinical evidence supporting their approval. This report describes an approach in which a “total evidence” network meta-analysis is performed that compares the biosimilar not only with the originator but also with the previous standard of care. This analysis was retrospectively applied to etanercept biosimilar in rheumatoid arthritis (end-point = ACR50). Using an increased number of evaluated patients (1,003 for network meta-analysis vs. 596 for equivalence trial), our results confirmed the equivalence index previously estimated from the approval trial of biosimilar.
Correspondence to:
Dr. Andrea Messori, PharmD
HTA Unit, ESTAR Toscana, Regional Health Service
Via San Salvi 12, 50100 Firenze, Italy
Email: [email protected]
Case
Report
Daptomycin-associated eosinophilic pneumonia with rechallenge: a case report
Melanie Nickerson, Ashish Bhargava, Pramodini Kale-Pradhan
Price
42.00 $
Page No. 521
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 6/2017 (521-524)
Daptomycin-associated eosinophilic pneumonia with rechallenge: a case report
Melanie Nickerson1, Ashish Bhargava2,3, and Pramodini Kale-Pradhan2,4
1Ascension, St. John Providence Macomb-Oakland Hospital, 2Ascension, St. John Hospital and Medical Center, Detroit, and 3School of Medicine, and 4Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA
Purpose: A case of daptomycin-associated acute eosinophilic pneumonia (AEP) with positive rechallenge is reported. Summary: AEP associated with daptomycin is reported in the literature, and the product labeling contains a warning and precaution statement. Criteria for diagnosing daptomycin-induced AEP varies and generally includes bronchoalveolar lavage (BAL) eosinophils ≥ 25%. We report a case of a 70-year-old woman with cough, shortness of breath, and altered mental status who presented ~ 9 days after starting therapy with daptomycin to treat methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. Daptomycin was utilized because of a presumed vancomycin allergy. Aspiration pneumonia was suspected and IV ampicillin and sulbactam was initiated. Clinical status improved initially but ~ 1 week later, her respiratory status declined. During work-up, peripheral eosinophils were abnormal at 11.6%, so daptomycin therapy was discontinued. BAL revealed 5% eosinophils with negative infectious work-up. Respiratory status rapidly improved after discontinuation of daptomycin. Linezolid therapy was initiated. Due to an uncertain association with daptomycin and concerns associated with long-term linezolid therapy, the patient agreed to rechallenge with daptomycin. Within 24 hours, respiratory symptoms returned and daptomycin was permanently discontinued. The patient rapidly recovered without the need for systemic corticosteroid treatment. Conclusions: Our case supports a broadened definition of pulmonary eosinophilia associated with daptomycin administration. It is important for clinicians to consider daptomycin as an etiology of pneumonia with abnormal eosinophils when other causes have been excluded. Clinicians could also consider peripheral eosinophilia as a possible indication of AEP when BAL is not available or cannot be obtained.
Correspondence to:
Prof. Pramodini B. Kale-Pradhan, PharmD
Department of Pharmacy Practice
Wayne State University and St. John Hospital and Medical Center
22101 Moross Road, Detroit, MI 48236, USA
Email: [email protected]
Facies dolorosa
Intrathecal analgesia by bupivacaine is not enhanced by coadministration of morphine in patients with severe cancer-related pain: a randomized double-blind cross-over study
Ingalill Reif, Anders Wincent, Carl-Olav Stiller
Price
42.00 $
Page No. 525
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 6/2017 (525-532)
Intrathecal analgesia by bupivacaine is not enhanced by coadministration of morphine in patients with severe cancer-related pain: a randomized double-blind cross-over study
Ingalill Reif1, Anders Wincent2, Carl-Olav Stiller3
1Department of Physiology and Pharmacology, Section of Anesthesiology and Intensive Care, 2Department of Anesthesiology, Surgical Services and Intensive Care Medicine (ANOPIVA Clinic), and 3Department of Medicine Solna, Clinical Pharmacology, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden
The objective of this randomized double blind cross-over trial was to determine if patients with severe cancer-related pain and inadequate response to systemic opioids prefer intrathecal (IT) pain relief with a combination of bupivacaine and morphine or bupivacaine only. Adult patients with cancer-related pain (n = 23) scheduled for IT analgesia at the Pain Center at the Karolinska University Hospital Solna, Stockholm, Sweden, were included. The optimal individual flow rate of IT bupivacaine (2 mg/mL) in addition to bolus doses was titrated and maintained for 4 days. Morphine (1 mg/mL) was added to bupivacaine either on day 2 or 4 according to a randomization protocol. Expression of pain relief preference for morphine instead of control (bupivacaine only) was the primary outcome. Secondary outcomes were difference in pain intensity, pain relief, total use of bupivacaine per 24 hours and number of requested bolus doses. Eight patients dropped out during the 4-day study period for reasons not related to the trial. IT bupivacaine significantly decreased median (interquartile range) pain intensity from 5 (3 – 7) at baseline (before catheter insertion) to 1 (0 – 1) (p = 0.0001; Wilcoxon test). Only 1 patient of 15 with 4-day data expressed any preference for morphine. The addition of IT morphine did not result in any significant change of pain intensity, pain relief score, total use of bupivacaine per 24 hours, or number of requested bolus doses. Conclusion: These results suggest that patients with cancer-related pain treated with high doses of systemic opioids, may start IT treatment with an optimal dose of IT bupivacaine without morphine.
Correspondence to:
Carl-Olav Stiller, PhD
Clinical Pharmacology L7:03
Karolinska University Hospital Solna
SE-171 76 Stockholm, Sweden
Email: [email protected]
Bioavailability Section
Pharmacokinetic comparison using two tablets of an evogliptin/metformin XR 2.5/500 mg fixed dose combination vs. 1 tablet each of evogliptin 5 mg and metformin XR 1,000 mg
Sumin Yoon, Su-jin Rhee, Sang-In Park, Seo Hyun Yoon, Joo-Youn Cho, In-Jin Jang, SeungHwan Lee, Kyung-Sang Yu
Price
42.00 $
Page No. 533
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 6/2017 (533-539)
Pharmacokinetic comparison using two tablets of an evogliptin/metformin XR 2.5/500 mg fixed dose combination vs. 1 tablet each of evogliptin 5 mg and metformin XR 1,000 mg
Sumin Yoon1, Su-jin Rhee1, Sang-In Park1, Seo Hyun Yoon1, Joo-Youn Cho1, In-Jin Jang1, SeungHwan Lee1,2, Kyung-Sang Yu1
1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, and 2Clinical Trials Center, Seoul National University Biomedical Research Institute, Seoul, Republic of Korea
Objectives: The aim of this study was to compare the pharmacokinetic (PK) characteristics of evogliptin and metformin following the administration of 2 evogliptin/metformin extended-release (XR) 2.5/500 mg FDC tablets with the coadministration of separate evogliptin 5-mg and metformin XR 1,000-mg tablets (separate formulations). Methods: A randomized, two-period, two-sequence crossover study was conducted. Subjects were randomly assigned to receive 2 FDC tablets or the individual tablets, followed by a 14-day washout period and the administration of the alternate treatment. Blood samples were collected predose and up to 72 hours postdose for each period. PK parameters including Cmax and AUClast were calculated. The geometric mean ratios (GMRs) and the 90% confidence intervals (CIs) between FDC and the separate formulations were calculated for the Cmax and AUClast of evogliptin and metformin. Results: 33 subjects completed the study. The GMR (90% CI) values of Cmax and AUClast for evogliptin were 1.011 (0.959 – 1.066) and 1.010 (0.977 – 1.043), respectively. The GMR (90% CI) values of Cmax and AUClast for metformin were 0.892 (0.827 – 0.963) and 0.893 (0.841 – 0.947), respectively. There was no significant difference between the FDC and separate formulations regarding the occurrence of adverse events. All drug-related adverse events were considered to be mild and resolved without any treatment. Conclusions: Two FDC tablets of evogliptin/metformin XR 2.5/500 mg showed a similar PK profile to the separate formulations of evogliptin 5 mg and metformin XR 1,000 mg. All of the 90% CIs of GMR satisfied the regulatory bioequivalence criteria of 0.800 – 1.250.
Correspondence to:
Kyung-Sang Yu, MD, PhD
Department of Clinical Pharmacology and Therapeutics
Seoul National University College of Medicine and Hospital
101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
Email: [email protected]
Bioavailability Section
Pharmacokinetics and relative bioavailability of two allopurinol tablets in healthy Chinese volunteers
Zhen-yan Hou, Hua-lin Cai, Yang Deng, Zhi-hua Li, Si-si Cao, Ying Chen, Yao Li, Miao Yan, Bi-kui Zhang
Price
42.00 $
Page No. 540
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 6/2017 (540-546)
Pharmacokinetics and relative bioavailability of two allopurinol tablets in healthy Chinese volunteers
Zhen-yan Hou1#2, Hua-lin Cai1#2#3, Yang Deng1#2#4, Zhi-hua Li1#2#3, Si-si Cao1#2#3, Ying Chen1#2#3, Yao Li1#2, Miao Yan1#2#3, Bi-kui Zhang1#2#3
1Department of Pharmacy, The Second Xiangya Hospital, 2Institute of Clinical Pharmacy, 3School of Pharmaceutical Science, Central South University, and 4Pharmaceutical College, Hunan University of Chinese Medicine, Changsha, China
Objective: To evaluate the pharmacokinetics and relative bioavailability of two allopurinol tablets in healthy Chinese volunteers. Methods: A single-center, randomized, cross-over, two-period study design was conducted in healthy male subjects who were identified as not carrying the HLA-B*58:01 allele. Under fasting conditions, a single oral dose of 300 mg test or reference tablets was given with a 1-week washout period. The blood samples were collected for up to 12 hours after the administration and the plasma concentrations of allopurinol were determined by high performance liquid chromatography. Subject interviews and physical examinations were done over regular intervals to monitor the adverse events. Results: 18 subjects were enrolled in the study, and none dropped out. The main pharmacokinetic parameters of allopurinol test and reference preparations were as follows: AUC0–tlast was 6,725.1 ± 1,390.0 ng×h×mL–1 and 6,425.6 ± 1,257.6 ng×h×mL–1; AUC0–∞ was 7,069.1 ± 1,503.2 ng×h×mL–1 and 6,750.6 ± 1,347.7 ng×h×mL–1; tmax was 1.3 ± 0.8 hours and 1.3 ± 0.8 hours; Cmax was 2,203.7 ± 557.4 ng×mL–1 and 2,310.8 ± 662.8 ng×mL–1; and T1/2 was 2.0 ± 1.6 hours and 1.7 ± 0.7 hours. The relative bioavailability was 105.1 ± 12.6%. The 90% confidence intervals for the geometric mean ratios (test/reference) of Cmax, AUC0–tlast, and AUC0–∞ of both preparations fell within the bioequivalence acceptance criteria (80 – 125%). No adverse events were found or reported during the study. Conclusion: The test allopurinol preparations and the reference preparations are bioequivalent and both are well tolerated.
Correspondence to:
Prof. Bi-kui Zhang and Dr. Miao Yan
Department of Pharmacy, The Second Xiangya Hospital, Central South University
Institute of Clinical Pharmacy, Central South University
Renmin Road 139#, Changsha 410011, China
Email: [email protected]
