Volume 54, No. 6/2016(June)
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Original Research
Population pharmacokinetics of IND/GLY (indacaterol/glycopyrronium) in COPD patients
Ivan Demin, Christian Bartels, Gordon Graham, Bruno Bieth, Aurélie Gautier, Hanns-Christian Tillmann, and Romain Sechaud
Price
42.00 $
Page No. 405
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 6/2016 (405-415)
Population pharmacokinetics of IND/GLY (indacaterol/glycopyrronium) in COPD patients
Ivan Demin1, Christian Bartels1, Gordon Graham1, Bruno Bieth1, Aurélie Gautier1, Hanns-Christian Tillmann2, and Romain Sechaud2
1Pharmacometrics, Novartis Pharma AG, and 2Novartis Institutes for Biomedical Research, Basel, Switzerland
Objective: Indacaterol/glycopyrronium (IND/GLY) is a fixed-dose combination (FDC) of indacaterol, an inhaled long-acting β2-agonist (LABA), and glycopyrronium, an inhaled long-acting muscarinic antagonist (LAMA), developed as a maintenance bronchodilator treatment for patients with chronic obstructive pulmonary disease (COPD). A population pharmacokinetic (PK) analysis was performed to describe the PK profiles of indacaterol and glycopyrronium following the twice daily (b.i.d.) and once daily (o.d.) inhalation regimens as FDC or as monotherapies and to determine the effect of covariates. Methods: PK data in 556 COPD patients were pooled from three phase 3 studies. Two phase 3 studies investigated IND/GLY 27.5/12.5 μg b.i.d. and the third study investigated IND/GLY 110/50 μg o.d. Body weight was included in the model with fixed allometric coefficients for indacaterol and glycopyrronium. Results: Statistically significant effects of smoking, age, and sex on apparent clearance of indacaterol; smoking, and estimated glomerular filtration rate at baseline on apparent clearance and Japanese ethnicity on apparent central volume of distribution of glycopyrronium were identified. Conclusion: Systemic exposure to indacaterol and glycopyrronium was shown to be dose-proportional and time-independent following inhalation either as monotherapies or FDC. None of the identified covariate effects was judged to be clinically relevant. There is no PK drug-drug interaction between indacaterol and glycopyrronium in its FDC.Correspondence to:
Ivan Demin, PhD
Novartis Pharma AG
Postfach, 4002 Basel, Switzerland
Email: [email protected]
Original Research
Construction of a database for published phase II/III drug intervention clinical trials for the period 2009 – 2014 comprising 2,326 records, 90 disease categories, and 939 drug entities
Sohyun Jeong, Nayoung Han, Boyoon Choi, Minji Sohn, Yun-Kyoung Song, Myeon-Woo Chung, Han-Sung Na, Eunhee Ji, Hyunah Kim, Ki Yon Rhew, Therasa Kim, In-Wha Kim, and Jung Mi Oh
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42.00 $
Page No. 416
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 6/2016 (416-425)
Construction of a database for published phase II/III drug intervention clinical trials for the period 2009 – 2014 comprising 2,326 records, 90 disease categories, and 939 drug entities
Sohyun Jeong1, Nayoung Han1, Boyoon Choi1, Minji Sohn1, Yun-Kyoung Song1, Myeon-Woo Chung5, Han-Sung Na5, Eunhee Ji2, Hyunah Kim3, Ki Yon Rhew4, Therasa Kim1, In-Wha Kim1, and Jung Mi Oh1
1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 2College of Pharmacy, Gacheon University, Incheon, 3College of Pharmacy, Sookmyung Women’s University, 4College of Pharmacy, Dongduk Women’s University, and 5Clinical Research Division, Toxicology Evaluation and Research Department, National Institute of Food and Drug Evaluation, Osong Health Technology Administration Complex, Chungcheongbuk-do, Korea
Objectives: To construct a database of published clinical drug trials suitable for use 1) as a research tool in accessing clinical trial information and 2) in evidence-based decision-making by regulatory professionals, clinical research investigators, and medical practitioners. Materials: Comprehensive information obtained from a search of design elements and results of clinical trials in peer reviewed journals using PubMed (http://www.ncbi.nlm.ih.gov/pubmed). Method: The methodology to develop a structured database was devised by a panel composed of experts in medical, pharmaceutical, information technology, and members of Ministry of Food and Drug Safety (MFDS) using a step by step approach. A double-sided system consisting of user mode and manager mode served as the framework for the database; elements of interest from each trial were entered via secure manager mode enabling the input information to be accessed in a user-friendly manner (user mode). Information regarding methodology used and results of drug treatment were extracted as detail elements of each data set and then inputted into the web-based database system. Results: Comprehensive information comprising 2,326 clinical trial records, 90 disease states, and 939 drugs entities and concerning study objectives, background, methods used, results, and conclusion could be extracted from published information on phase II/III drug intervention clinical trials appearing in SCI journals within the last 10 years. The extracted data was successfully assembled into a clinical drug trial database with easy access suitable for use as a research tool. The clinically most important therapeutic categories, i.e., cancer, cardiovascular, respiratory, neurological, metabolic, urogenital, gastrointestinal, psychological, and infectious diseases were covered by the database. Names of test and control drugs, details on primary and secondary outcomes and indexed keywords could also be retrieved and built into the database. The construction used in the database enables the user to sort and download targeted information as a Microsoft Excel spreadsheet. Conclusion: Because of the comprehensive and standardized nature of the clinical drug trial database and its ease of access it should serve as valuable information repository and research tool for accessing clinical trial information and making evidence-based decisions by regulatory professionals, clinical research investigators, and medical practitioners.Correspondence to:
Jung Mi Oh
College of Pharmacy and Research
Institute of Pharmaceutical Sciences
Seoul National University
1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea
Email: [email protected]
Original Research
Effects of pretreatment with different doses of cisatracurium on succinylcholine-induced fasciculations
Zhuan Zhang, Dong-sheng Zhang, Wei Sui, Xu-hong Liu, Luo Zhang, and Jian-hong Sun
Price
42.00 $
Page No. 426
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 6/2016 (426-432)
Effects of pretreatment with different doses of cisatracurium on succinylcholine-induced fasciculations
Zhuan Zhang, Dong-sheng Zhang, Wei Sui, Xu-hong Liu, Luo Zhang, and Jian-hong Sun
Department of Anesthesiology, Yangzhou No. 1 Peoples’ Hospital, Yangzhou, China
Objective: To compare the effects of different doses of cisatracurium pretreatment on succinylcholine-induced fasciculations. Methods: 90 patients scheduled for laparoscopic cholecystectomies were equally randomized into three groups to receive pretreatment of 0.005, 0.01, and 0.02 mg/kg cisatracurium, respectively. After the pretreatments, general anesthesia was induced 3.5 minutes later, train-of-four stimulation was monitored 4.5 minutes later, succinylcholine 1.5 mg/kg was injected 5 minutes later, and endotracheal intubation was implemented 6.5 minutes later. Side effects of cisatracurium, intensity of fasciculations, intubating conditions, time and extent to maximal depression of twitch and time for its recovery to 20% of control value, and severity of myalgia at 24 hours postoperatively were recorded. Results: Fasciculations were alleviated significantly after the cisatracurium pretreatment of 0.02 mg/kg, more than with the other two doses (p < 0.01). Intubating conditions, time and extent to maximal depression of twitch, time for its recovery to 20% of the controls, and incidence of myalgia had no significant changes among the three groups (p > 0.05). Transient and tolerable diplopia and difficulty opening eyes emerged after pretreatment of 0.02 mg/kg cisatracurium. Conclusion: The pretreatment of 0.02 mg/kg cisatracurium given 5 minutes before succinylcholine injection could alleviate succinylcholine-induced fasciculations without influence on muscle relaxation effects or endotracheal intubating conditions, but did not affect the occurrence of myalgia, and might produce transient diplopia and difficulty opening eyes.Correspondence to:
Jian-hong Sun, MD
Department of Anesthesiology
Yangzhou No. 1 Peoples’ Hospital
368 Middle Hanjiang Road, Yangzhou, 225012, China
Email: [email protected]
Original Research
Population pharmacokinetic characteristics of sirolimus in healthy Chinese subjects and renal transplant patients
Miao Wang, Bao-ling Duan, Yin-jin Yuan, Xia Su, Hang Zheng, Fu-sheng Wang, and He Sun
Price
42.00 $
Page No. 433
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 6/2016 (433-441)
Population pharmacokinetic characteristics of sirolimus in healthy Chinese subjects and renal transplant patients
Miao Wang1,2, Bao-ling Duan2, Yin-jin Yuan3, Xia Su1, Hang Zheng1, Fu-sheng Wang2, and He Sun1
1School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 2National Engineering Research Center of Microbial Medicine, New Drug Research and Development Centre of North China Pharmaceutical Group Corporation, Hebei, and 3School of Chemical Engineering and Technology, Tianjin University, Tianjin, China
Aim: To identify the factors affecting the pharmacokinetics (PKs) of sirolimus in healthy Chinese subjects and renal transplant patients. Methods: A population PK model of sirolimus was constructed using dense data from 22 healthy volunteers and sparse data from 105 renal transplant patients. Results: The data were well described by a two-compartment model with first-order absorption. The estimates of absorption rate constant (Ka), clearance (CL/F), and central volume of distribution (V2/F) were 0.24 h–1, 8.81 L/h, and 676 L, respectively. The CL/F in renal transplant patients was 45.5% lower than that in healthy subjects. Based on the final model, CL/F decreased significantly with increasing cyclosporine (CsA) daily dose and age. A decrease of 7.3% in CL/F for every 100-mg increase in the CsA daily dose and a decrease of 34.2% in CL/F for every 20-year increase in age was observed. Moreover, V2/F increased significantly with increasing serum creatinine in our study. However, the range of serum creatinine concentration and the interindividual variability for V2/F are large. Conclusion: This is the first study to characterize the population PKs of sirolimus using a two-compartment model in healthy Chinese subjects and renal transplant patients. A decrease of 7.3% in the sirolimus CL/F for every 100-mg increase in the CsA daily dose and a decrease of 34.2% in the sirolimus CL/F for every 20-year increase in age was observed, which allowed us to better optimize sirolimus dosing regimens in Chinese renal transplant patients.Correspondence to:
Prof. He Sun, PhD
School of Pharmaceutical Science and Technology
Tianjin University
No.92 Weijin Rd. Nankai District, Tianjin, 300072, PR China
Email: [email protected]
Original Research
Compartmental approach to assess bioequivalence compared to the noncompartmental approach
Sung Eun Kim, Renhua Zheng, Dongwoo Kang, and Bo-Hyung Kim
Price
42.00 $
Page No. 442
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 6/2016 (442-449)
Compartmental approach to assess bioequivalence compared to the noncompartmental approach
Sung Eun Kim1, Renhua Zheng2, Dongwoo Kang3, and Bo-Hyung Kim2
1Department of Pharmacy, Seoul National University Hospital, 2Department of Clinical Pharmacology and Therapeutics, Kyung Hee University College of Medicine and Hospital, Seoul, Republic of Korea, and 3Translational Medicine and Clinical Pharmacology, Daiichi Sankyo Pharma Development, Edison, NJ, USA
Objective: The objective of this study is to evaluate the relative performance of individual or population compartmental analysis (ICA or PCA) vs. noncompartmental analysis (NCA) in estimating the systemic exposures of drugs to assess bioequivalence (BE) between original and generic formulations in the case of limited datasets. Methods: BE study data of adefovir, finasteride, and tiropramide were chosen. The analyses were performed for the 1) original dataset, 2) limited dataset with small size for which the number of subjects was decreased to half, and 3) limited dataset with minimal-sampling timepoint of 9 samples. As for NCA and ICA, the Cmax and AUCinf were estimated using WinNonlin®. The PCA was implemented in NONMEM® and then Monte Carlo simulation was utilized to generate 10,000 sets of Cmax and AUCinf. Results: The 90% confidence intervals (CIs) of the original datasets of the 3 drugs were all within BE acceptance criteria regardless of the analysis method. For small-samplesize datasets of adefovir and finasteride, BE results were maintained. In tiropramide, the lower boundary of CI computed from ICA or PCA results was less than 0.800 for the 3 small sample sizes (n = 22, 16, 10), but that of NCA results was less than 0.800 for only the smallest sample size (n = 10). As for the minimal-sampling timepoint, results were within the BE acceptance criteria for all of the 3 analyses. Conclusions: Compartmental approaches can provide a complementary method for BE assessment, as well as being used for restricted-design studies.Correspondence to:
Bo-Hyung Kim, MD, PhD
Department of Clinical Pharmacology and Therapeutics
Kyung Hee University College of Medicine and Hospital
23 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-872, Korea
Email: [email protected]
Original Research
Prevalence of overweight in schizophrenia patients in Asia: findings of the research on Asian psychotropic prescription patterns (REAP) study
Fei Wang, Yu-Tao Xiang, Gabor S. Ungvari, Chee H. Ng, Helen F.K. Chiu, Wei Zheng, Chay-Hoon Tan, and Naotaka Shinfuku
Price
42.00 $
Page No. 450
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]
Original Research
Pharmacokinetic properties and bioequivalence of spironolactone tablets in fasting and fed healthy Chinese male subjects
Zhi-hua Li, Yang Deng, Hua-lin Cai, Zhao-hui Guo, Zhen-yan Hou, Ge Wu, Miao Yan, and Bi-kui Zhang
Price
42.00 $
Page No. 455
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 6/2016 (455-461)
Pharmacokinetic properties and bioequivalence of spironolactone tablets in fasting and fed healthy Chinese male subjects
Zhi-hua Li1,3*, Yang Deng4*, Hua-lin Cai1,2, Zhao-hui Guo1,3, Zhen-yan Hou1, Ge Wu1,3,5, Miao Yan1,2, and Bi-kui Zhang1,2
1Department of Pharmacy, the Second Xiangya Hospital, 2Institute of Clinical Pharmacy, 3School of Pharmaceutical Science, Central South University, 4Pharmaceutical College, Hunan University of Chinese Medicine, and 5Changsha Central Hospital, Changsha, China
Background and purpose: Spironolactone is a potassium-sparing diuretic and is a competitive antagonist of aldosterone, which is widely used in the treatment of primary aldosteronism, essential hypertension, congestive cardiac failure, and various edematous states. The purpose of this study was to compare the pharmacokinetic properties and bioequivalence of the two formulations of spironolactone tablets in healthy Chinese male subjects under fasting and fed condition. Methods: A total of 40 male subjects were enrolled in this randomized, open-label, two-period crossover study, subjects in 2 groups (20 individuals in each group) received a single 100-mg dose of test or reference spironolactone tablet formulations with a 2-week washout period under both fasting and fed condition. The plasma concentrations of canrenone, a major active metabolite of spironolactone, were quantified by a validated high performance liquid chromatography-tandem mass spectrometry method. The pharmacokinetic parameters including AUC0–tlast, AUC0–∞, tmax, and Cmax were employed to test bioequivalence. Results: The relative bioavailability was 99.2 ± 11.6% and 97.6 ± 7.4% under fasting and fed condition, respectively. The 90% confidence intervals of the adjusted geometric mean ratio (test/reference) of Cmax, AUC0–tlast, and AUC0–∞ were 89.7 – 113.8%, 93.9 – 103.3%, and 90.0 – 103.0% in fasting study and 87.7 – 102.3%, 95.1 – 99.5%, and 94.1 – 98.9% in fed study, respectively. Conclusions: Based on pharmacokinetic parameters and the Chinese Food and Drug Administration’s guidance and regulatory criteria for bioequivalence, the test and reference formulations of spironolactone were bioequivalent under both fasting and fed condition. Both formulations were generally well tolerated, with no adverse reaction reported.
*Zhi-hua Li and Yang Deng contributed equally to this work.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] and [email protected]
Original Research
Effect of ABCB1 rs12720464 and rs1055302 polymorphisms in Chinese patients on the time course of action of rocuronium administered as a single dose
Tian-long Qi, Yin-hui Zhou, Jing-jing Yuan, Zhi-song Li, Zhong-yu Wang, Yan-zi Chang, Er-xian Zhao, Dan Cheng, Jun-kai Hou, Yan Tian, Ge-zi Chen, Yuan-yuan Mao, Yang Ren, Li-rong Zhang, Quan-cheng Kan, and Wei Zhang
Price
42.00 $
Page No. 462
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 6/2016 (462-470)
Effect of ABCB1 rs12720464 and rs1055302 polymorphisms in Chinese patients on the time course of action of rocuronium administered as a single dose
Tian-long Qi1, Yin-hui Zhou1, Jing-jing Yuan1, Zhi-song Li1, Zhong-yu Wang1, Yan-zi Chang1, Er-xian Zhao1, Dan Cheng1, Jun-kai Hou1, Yan Tian1, Ge-zi Chen1, Yuan-yuan Mao1, Yang Ren1, Li-rong Zhang2, Quan- cheng Kan3, and Wei Zhang1
1Anesthesiology Department in the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 2Department of Pharmacology, School of Medicine, Zhengzhou, 3Clinical Pharmacology Base, The Open Key Clinical Medical Experimental Laboratory Institute of Henan Province, First Affiliated Hospital, Zhengzhou University, Zhengzhou, China
Objective: To determine whether ABCB1 gene polymorphisms affect the time course of action of rocuronium in Chinese patients. Methods: This study included 105 unrelated Chinese patients undergoing general anesthesia with propofol, fentanyl, and rocuronium. Neuromuscular monitoring was performed with calibrated acceleromyography. Patients were allowed to recover spontaneously from the neuromuscular block. The time interval between the first maximum depression of the train of four (TOF) and spontaneous recovery TOF ratio of 0.25/0.7/0.8/0.9 was recorded. The Sequenom MassArray® single-nucleotide polymorphism (SNP) detection technology was used to detect the genotypes of the ABCB1 rs12720464, rs1055302. Demographic and non-genetic clinical data were also collected. Results: In the present study, the mean time to spontaneous recovery of TOF ratio 0.8/0.9 in ABCB1 rs12720464 GG genotype was longer compared to that observed in ABCB1 rs12720464 AG genotype (56.77 ± 14.23 minutes vs. 49.50 ± 10.49 minutes, and 62.58 ± 18.16 minutes vs. 53.20 ± 12.56 minutes, respectively, p < 0.05). Further, the time to spontaneous recovery of TOF 0.7/0.8/0.9 in ABCB1 rs1055302 GG genotype was longer than that in ABCB1 rs1055302 AG genotype (52.00 ± 12.10 minutes vs. 44.83 ± 7.38 minutes, 55.96 ± 13.92 minutes vs. 46.83 ± 7.67 minutes, 61.66 ± 17.70 minutes vs. 49.50 ± 8.44 minutes, respectively, p < 0.05). Conclusion: In Chinese patients who were administered a single dose of rocuronium, the genetic variants ABCB1 rs12720464, and rs1055302 contribute to the individual< variability of time course of action.Correspondence to:
Prof. Wei Zhang, PhD
Anesthesiology Department
First Affiliated Hospital, Zhengzhou University
Zhengzhou, Henan 450052, China
Email: [email protected]
Short Report
Vincristine-induced paralytic ileus during induction therapy of treatment protocols for acute lymphoblastic leukemia in adult patients
Takeo Yasu, Nobuhiro Ohno, Toyotaka Kawamata, and Yosuke Kurokawa
Price
42.00 $
Page No. 471
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 6/2016 (471-473)
Vincristine-induced paralytic ileus during induction therapy of treatment protocols for acute lymphoblastic leukemia in adult patients
Takeo Yasu1, Nobuhiro Ohno2, Toyotaka Kawamata2, and Yosuke Kurokawa1
1Department of Pharmacy, and 2Department of Hematology/Oncology, The Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Vincristine (VCR) is an important drug used in the treatment of acute lymphoblastic leukemia (ALL). VCR-induced neurotoxicity can manifest as peripheral neuropathy, constipation, or paralytic ileus. While there are some case reports describing VCR-induced paralytic ileus (VIPI) in pediatric ALL, there are fewer publication on adult ALL patients. Therefore, we retrospectively investigated VIPI during induction therapy of treatment protocols for ALL in 19 adult patients. The incidence of VIPI was 32%. VIPI was significantly increased in patients receiving concomitant itraconazole (ITCZ) (p = 0.04). We recommend avoidance of the combination of VCR and ITCZ.Correspondence to:
Takeo Yasu, PhD
The Research Hospital
The Institute of Medical Science
The University of Tokyo
4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
Email: [email protected]
Short Report
Prolonged effects of miconazole oral gel on warfarin anticoagulation even after treatment withdrawal
Satoshi Murakami, Akihiro Tanaka, Keiko Ido, Mamoru Tanaka, and Hiroaki Araki
Price
42.00 $
Page No. 474
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 6/2016 (474-476)
Prolonged effects of miconazole oral gel on warfarin anticoagulation even after treatment withdrawal
Satoshi Murakami, Akihiro Tanaka, Keiko Ido, Mamoru Tanaka, and Hiroaki Araki
Division of Pharmacy, Ehime University Hospital, Toon, Japan
Objective: We investigated the effect of terminating miconazole oral gel (MOG) treatment on the anticoagulant activity of warfarin by evaluating changes in international normalized ratio levels (INR). Methods: Data were collected from the medical records of 6 patients treated with warfarin and MOG. Results: Following cessation of MOG treatment, increased INR and INR/dose levels were observed for an average of 15 days, showing that the anticoagulant activity of warfarin was increased for ~ 2 weeks. Conclusions: Closer monitoring of INR levels for at least 2 weeks may be required upon withdrawal of MOG treatment in patients treated with warfarin.Correspondence to:
Akihiro Tanaka,PhD
Division of Pharmacy, Ehime University Hospital
454 Shitsukawa, Toon, Ehime 791-0295, Japan
Email: [email protected]
Bioavailability Section
Pharmacokinetics and bioavailability in healthy Chinese volunteers of a novel rabeprazole sterile powder formulation for injection
Zhongying Ma, Chengtao Lu, Jiankang Li, Fan Li, Xueqing Li, Ying Song, Jie Ge, and Aidong Wen
Price
42.00 $
Page No. 477
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 6/2016 (477-483)
Pharmacokinetics and bioavailability in healthy Chinese volunteers of a novel rabeprazole sterile powder formulation for injection
Zhongying Ma*, Chengtao Lu*, Jiankang Li, Fan Li, Xueqing Li, Ying Song, Jie Ge, and Aidong Wen
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, China
Rabeprazole sterile powder for injection (RSPI) is a new formulation, compared with rabeprazole enteric coated tablets. The aim of this study was to evaluate the pharmacokinetic properties and bioavailability of RSPI in healthy Chinese volunteers. Pharmacokinetic studies included an ascending single dose of 10, 20, 40 mg, and a multiple doses of 20 mg. A bioavailability study was evaluated following a single dose of 20 mg between RSPI and Pariet® Pharmacokinetic parameters of rabeprazole given in each treatment period were calculated using non-compartmental analysis. In the PK study, after a single intravenous dose of 10, 20, and 40 mg, the main pharmacokinetic parameters for rabeprazole were as follows: Cmax 566.88, 897.23, 2,171.6 ng/mL; AUClast/794.31, 1,122.76, 2,446.85 ng×h/mL, respectively. After multiple doses of 20 mg, the main pharmacokinetic parameters for rabeprazole were Cmax 991.90 ng/mL, AUClast 1,261.08 ng×h/mL. In the BA study, after a single oral dose of Pariet® 20 mg, the main pharmacokinetic parameters for rabeprazole were Cmax 582.74 ng/mL, AUClast 1,135.5 ng×h/mL. RSPI produced a lessthan-proportional increase in exposure with increasing dose in healthy subjects. The accumulation ratio was 1.0, suggesting RSPI displayed no accumulation after repeated administration. The bioavailability of RSPI was increased by ~ 11% as measured by AUClast compared with Pariet® after a single oral administration.
*Zhongying Ma and Chengtao Lu contributed equally.Correspondence to:
Prof. Aidong Wen
Department of Pharmacy, Bijing Hospital
Fourth Military Medical University
Xi’an, P.O. Box 710032, China
Email: [email protected]
Bioavailability Section
Bioequivalence and food effect study of enteric-coated mesalazine tablets in healthy Chinese volunteers by HPLC-ESI-MS/MS
Zhao-hui Guo, Yang Deng, Hua-lin Cai, Huan-de Li, Zhi-hua Li, Miao Yan, and Bi-kui Zhang
Price
42.00 $
Page No. 484
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 6/2016 (484-494)
Bioequivalence and food effect study of enteric-coated mesalazine tablets in healthy Chinese volunteers by HPLC-ESI-MS/MS
Zhao-hui Guo1#3*, Yang Deng1#2*, Hua-lin Cai1#3, Huan-de Li1#3, Zhi-hua Li1#3, Miao Yan1#3, and Bi-kui Zhang1#3
1Department of Pharmacy, Second Xiangya Hospital, Central South University, Institute of Clinical Pharmacy, Central South University, Changsha, 2School of Pharmacy, Hunan University of Chinese Medicine, Changsha, and 3School of Pharmaceutical Science, Central South University, Changsha, China
Objective: To establish a developed HPLC-ESI-MS/MS method for simultaneous determination of mesalazine (5-ASA) and its major metabolite N-Ac-5-ASA in human plasma and to investigate bioequivalence of two enteric-coated mesalazine tablets as well as the effect of highfat food on the pharmacokinetics of 5-ASA and N-Ac-5-ASA. Methods: In this open-label, randomized, crossover, two-states, fourperiod study, 20 healthy Chinese volunteers were randomized to receive a single oral dose of trial or reference preparation (2 × 250 mg) under fasting and fed state. Plasma samples were obtained at 0, 1, 2, 3, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 24, and 36 hours postdose and were measured by a developed HPLC-ESI-MS/MS method. Safety and tolerability were assessed throughout the study. Results: The HPLC-ESI-MS/MS method required only 7.0 minutes run time and was successfully applied in analyzing ~ 2,000 samples. High-fat-food administration prolonged tmax of 5-ASA and N-Ac-5-ASA (p < 0.05), while AUC was not significantly affected by the meal (p > 0.05). The 90% confidence intervals (CIs) of the fed/fasting and trial/reference ratios of log-transformed Cmax and AUC were within 80 – 125%. The two one-sided t-tests showed that the trial and reference preparation were bioequivalent (p > 0.05). Conclusions: This developed HPLC-ESI-MS/MS method is suitable for massive biomedical analysis. Trial and reference preparations are bioequivalent under fasting and fed state. High-fat-food administration delays the absorption of mesalazine while total exposure is not affected. Dietary habits should always be taken into consideration when enteric-coated mesalazine tablets were prescribed to patients.
*These authors contributed equally to this work.Correspondence to:
Prof. Bi-kui Zhang and Dr. Miao Yan
Department of Pharmacy, Second Xiangya Hospital
Central South University, Institute of Clinical Pharmacy
Central South University
Changsha, 410011, China
Email: [email protected] and [email protected]
