Volume 51, No. 5/2013(May)
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Original
The impact of allergic rhinitis and its treatment on the pharmacokinetics of nasally administered fentanyl
Michael Perelman, Anthony N. Fisher, Alan Smith and Alastair Knight
Price
42.00 $
Page No. 349
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 51 – No. 5/2013 (349-356)
Impact of allergic rhinitis and its treatment on the pharmacokinetics of nasally administered fentanyl
Michael Perelman1, Anthony N. Fisher1, Alan Smith1 and Alastair Knight2
1Archimedes Development Limited, Albert Einstein Centre, Nottingham Science and Technology Park, University Boulevard, Nottingham, and 2Evicom Limited, Langdon Park, Teddington, UK
Objectives: Fentanyl pectin nasal spray (FPNS, Lazanda® in the US and PecFent® in Europe and Australia) is a novel analgesic approved for the management of breakthrough pain in cancer patients. Given that the fentanyl is nasally administered, it is important to understand whether concomitant allergic rhinitis, or its treatment with a vasoconstrictor, would affect its absorption and, potentially, its efficacy or safety. Methods and subjects: Subjects with a history of allergic rhinitis were screened to identify subjects who developed at least moderate rhinitis symptoms on exposure to pollen allergen (either ragweed or tree) in an environmental exposure chamber (EEC). These were entered into a randomized, three-way crossover study in which each subject received 100 μg of FPNS under three exposure conditions; Control (no rhinitis), Rhinitis (symptomatic without decongestant), Treated (symptomatic with concomitant oxymetazoline). Blood samples for fentanyl were collected over a 24-hour period. Results: A total of 132 subjects was screened to identify 54 for inclusion in the study; 31 were evaluable for pharmacokinetics. Measures of fentanyl absorption (mean or median) were similar between Control and Rhinitis conditions: Cmax 453.0 vs. 467.8 pg/ml; AUCt 1,292.3 vs. 1,325.4 pg×h/ml, AUC0-∞ 1,430.6 vs. 1,387 pg×h/ml and tmax 20 vs. 17 minutes. When oxymetazoline was co-administered, overall fentanyl absorption was slightly reduced (AUC0-∞ 1,362.4 pg×h/ml); but, more clinically relevant were the delayed rate of absorption (tmax 53 minutes) and reduced Cmax (235.3 pg/ml). Conclusions: Patients treated with FPNS will be unaffected by the development of allergic rhinitis; but, if oxymetazoline is prescribed, the patient would benefit from added supervision when oxymetazoline is started and stopped.Correspondence to:
Alan Smith, PhD
Archimedes Development Ltd.
Albert Einstein Centre
Nottingham Science and Technology Park
University Boulevard, Nottingham, NG7 2TN, UK
Email: [email protected]
Original
Population pharmacokinetic and pharmacodynamic analyses of teicoplanin in Japanese patients with systemic MRSA infection
Ryuichi Ogawa, Seiichi Kobayashi, Yuki Sasaki, Mizue Makimura and Hirotoshi Echizen
Price
42.00 $
Page No. 357
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 51 – No. 5/2013 (357-366)
Population pharmacokinetic and pharmacodynamic analyses of teicoplanin in Japanese patients with systemic MRSA infection
Ryuichi Ogawa1, Seiichi Kobayashi2, Yuki Sasaki3, Mizue Makimura3 and Hirotoshi Echizen1
1Department of Pharmacotherapy, 2Graduate School of Clinical Pharmacy, Meiji Pharmaceutical University, and 3Department of Hospital Pharmacy, Nihon University School of Medicine Itabashi Hospital, Tokyo, Japan
Background: Teicoplanin is a glycopeptide antibiotic used for the treatment of MRSA infection. An initial loading dose of 400 mg every 12 hours for three doses is the standard dosing regimen. This study aimed to assess whether this regimen was appropriate based on the pharmacokinetic/pharmacodynamic (PK/PD) analyses in Japanese patients. Methods: We conducted a population pharmacokinetic (PPK) analysis of teicoplanin by NONMEM using serum drug concentrations obtained from 116 patients with MRSA infection. PD of the drug was analyzed by a model assuming that the variability of therapeutic responses (assessed by body temperature, serum C-reactive protein concentrations, and white blood cell counts) on the 3rd, 7th or 14th day of treatment is associated with the logarithm of serum unbound drug concentration (Cmax,unbound) divided by the MIC against MRSA (log[Cmax,unbound/MIC]). Results: The final PPK model showed that creatinine clearance and serum albumin concentration were significant (p < 0.01) covariates of systemic clearance and peripheral volume of distribution of teicoplanin, respectively. The PD analyses indicated that log[Cmax,unbound/MIC] of 0.30 on Day 3 of teicoplanin therapy was the threshold for achieving successful clinical responses. Integrating the PK and PD data, we consider that the standard loading dose regimen would attain the threshold serum level within the initial 3 days in only less than 50% of the patients. Conclusion: We propose that an extended loading regimen (400 mg every 12 hours for the first 5 doses) would be a treatment option to maximize the therapeutic effects of teicoplanin in patients with systemic MRSA infection.Correspondence to:
Ryuichi Ogawa, PhD
Department of Pharmacotherapy
Meiji Pharmaceutical University
2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan
Email: [email protected]
Original
Time to onset of analgesia following local infiltration of liposome bupivacaine in healthy volunteers: a randomized, single-blind, sequential cohort, crossover study
Glen Apseloff, Erol Onel and Gary Patou
Price
42.00 $
Page No. 367
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 51 – No. 5/2013 (367-373)
Time to onset of analgesia following local infiltration of liposome bupivacaine in healthy volunteers: a randomized, single-blind, sequential cohort, crossover study
Glen Apseloff1, Erol Onel2 and Gary Patou2
1The Ohio State University College of Medicine, Department of Pharmacology, Division of Clinical Pharmacology, Columbus, OH, and 2Pacira Pharmaceuticals, Inc., San Diego, CA, USA
Background/Objective: Bupivacaine liposome injectable suspension is a novel, prolonged-release formulation of bupivacaine. The time to onset of analgesia following an injection of liposome bupivacaine compared with placebo (normal saline) was investigated using a novel incisional pain model. Bupivacaine HCl was used as a positive control, compared with placebo to verify the validity of the study. Materials and methods: In this Phase 1, single-blind, crossover study, healthy volunteers (n = 132) were randomized to four sequential cohorts to receive subcutaneous normal saline in one arm and either liposome bupivacaine 40 mg or bupivacaine HCl 7.5 mg in the other. At 30, 15, 5, and 2 minutes after study drug administration for Cohorts 1 – 4 respectively, an incision was made in each arm and 18% acetic acid solution was applied to elicit pain. The primary outcome measure was a subject’s assessment of pain intensity on a 100 mm visual analog scale. Results: Statistically significant differences in pain intensity scores between liposome bupivacaine and normal saline were observed at 30, 15, 5, and 2 minutes postdose; similar findings were reported for bupivacaine HCl vs. normal saline. Both liposome bupivacaine and bupivacaine HCl were well tolerated and achieved > 30% pain reduction, normalized to placebo, within 5 minutes. Conclusions: These results indicate that liposome bupivacaine offers time to onset characteristics similar to traditional bupivacaine HCl: clinically meaningful analgesia within 2 minutes after administration and substantial analgesia by 5 minutes.Correspondence to:
Prof. Glen Apseloff, MD, FCP
The Ohio State University College of Medicine
Department of Pharmacology
Division of Clinical Pharmacology
5086 Graves Hall, 333 W. 10th Avenue
Columbus, OH 43210, USA
Email: [email protected]
Original
Pharmacokinetic model incorporating mechanism-based inactivation of CYP2D6 can explain both non-linear kinetics and drug interactions of paroxetine
Akiko Mikami, Hisakazu Ohtani, Satoko Hori and Yasufumi Sawada
Price
42.00 $
Page No. 374
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 51 – No. 5/2013 (374-382)
Pharmacokinetic model incorporating mechanism-based inactivation of CYP2D6 can explain both non-linear kinetics and drug interactions of paroxetine
Akiko Mikami1, Hisakazu Ohtani2, Satoko Hori1,3 and Yasufumi Sawada1
1Department of Drug Informatics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 2Department of Clinical Pharmacy, Keio University Faculty of Pharmacy, and 3Interfaculty Initiative in Information Studies, The University of Tokyo, Tokyo, Japan
Objective: To develop a pharmacokinetic model able to describe the nonlinear pharmacokinetics of paroxetine (PRX) and to predict the drug-drug interaction between PRX and metoprolol under various dosage regimens. Methods: A pharmacokinetic model of PRX incorporating mechanism-based inhibition was developed. This model was fitted to the drug concentration profiles obtained after single and repeated administrations of PRX to estimate the pharmacokinetic parameters of PRX and degradation rate constant of cytochrome P450 (CYP) 2D6. It was also fitted to the time profile of S-metoprolol after coadministration of metoprolol and PRX, and the fractional contribution of CYP2D6 to overall clearance of S-metoprolol was estimated. Using the developed model and estimated parameters, an optimal dosage regimen for metoprolol during withdrawal of PRX was simulated. Results: The developed model well described the time profiles of both PRX and metoprolol concentration during concomitant administration. The estimated parameters were consistent with reported values. The nonlinear and accumulation properties of PRX could be explained by mechanism-based inhibition of CYP2D6 by PRX. Upon tapering PRX from 20 mg/ day to 10 mg/day for 14 days then 5 mg/day for 14 days until cessation, the optimal dosage regimen to resume 120 mg/day of metoprolol based on the developed model was as follows: 30 mg/day during concomitant administration, 40 mg/day for the next 14 days, 60 mg/day for the next 14 days, and finally 120 mg/day. Conclusions: The developed model enabled us to quantitatively estimate drug-drug interactions of PRX and CYP2D6 substrate drugs, and to predict optimal dosage regimens.Correspondence to:
Prof. Yasufumi Sawada
Laboratory of Drug Informatics
Graduate School of Pharmaceutical Sciences
The University of Tokyo
7-3-1 Hongo, Bunkyoku, Tokyo 113-0033, Japan
Email: [email protected]
Original
Effects of genetic polymorphisms of OPRM1, ABCB1, CYP3A4/5 on postoperative fentanyl consumption in Korean gynecologic patients
Kye-Min Kim, Ho-Sook Kim, Se Hun Lim, Soon Ho Cheong, Eun-Jung Choi, Hyun Kang, Hey-Ran Choi, Jin-Woo Jeon, Jun Heum Yon, Minkyung Oh and Jae-Gook Shin
Price
42.00 $
Page No. 383
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 51 – No. 5/2013 (383-392)
Effects of genetic polymorphisms of OPRM1, ABCB1, CYP3A4/5 on postoperative fentanyl consumption in Korean gynecologic patients
Kye-Min Kim1, Ho-Sook Kim2,3, Se Hun Lim4, Soon Ho Cheong4, Eun-Jung Choi2, Hyun Kang5, Hey-Ran Choi6, Jin-Woo Jeon1, Jun Heum Yon1, Minkyung Oh2 and Jae-Gook Shin2,3
1Department of Anesthesiology and Pain Medicine, Inje University Sanggye Paik Hospital, Seoul 2Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, 3Department of Clinical Pharmacology, 4Department of Anesthesiology and Pain Medicine, Inje University Busan Paik Hospital, 5Department of Anesthesiology and Pain Medicine, College of Medicine, Chung-Ang University, and 6Department of Anesthesiology and Pain Medicine, Inje University Seoul Paik Hospital, Seoul, Republic of Korea
Objective: Fentanyl, a μ-opioid receptor agonist, is a substrate of P-glycoprotein. Its metabolism is catalyzed by CYP3A4 and CYP3A5. The aim of this study was to investigate the association between postoperative fentanyl consumption and genetic polymorphisms of μ-opioid receptor (OPRM1), ABCB1 (gene encoding P-glycoprotein), CYP3A4 and CYP3A5 in Korean patients. Methods: 196 female patients scheduled to undergo total abdominal hysterectomy or laparoscopic assisted vaginal hysterectomy under general anesthesia were enrolled in this study. Intravenous patient-controlled analgesia with fentanyl was provided postoperatively. Cumulative fentanyl consumption was measured during the first 48 hours postoperatively. The severity of pain at rest was assessed with the visual analogue scale. OPRM1 118A>G, ABCB1 2677G>A/T, ABCB1 3435C>T, CYP3A4*18 and CYP3A5*3 variant alleles were genotyped. The effects of genetic and non-genetic factors on fentanyl requirements were evaluated with multiple linear regression analysis. Results: The 24-hour cumulative fentanyl doses were significantly associated with pain core, weight and type of surgery (p < 0.05). The 48-hour cumulative fentanyl doses were significantly associated with pain score, type of surgery and history of PONV or motion sickness (p < 0.05). Genetic polymorphisms were not associated with fentanyl requirements. Conclusion: In Korean gynecologic patients, no association was found between genetic factors and postoperative fentanyl consumption.Correspondence to:
Kye-Min Kim, MD, PhD
Department of Anesthesiology and Pain Medicine
Inje University Sanggye Paik Hospital
1342, Dongil-ro, Nowon-gu
Seoul, 139-707 Republic of Korea
or
Jae-Gook Shin, MD, PhD
Department of Pharmacology and PharmacoGenomics Research Center
Inje University College of Medicine
Department of Clinical Pharmacology
Inje University Busan Paik Hospital
Busan, Republic of Korea
Email: [email protected] or [email protected]
Original
Pharmacokinetics and efficacy of ropivacaine in Chinese patients following intra-articular administration
Saizhen Chen, Zhongyi Chen, Yinxiu Jin, Ziyou Tian, Xuezheng Lin, Mengyong Zhu, Shanshan Xu, Jiamiao Lin and Lijun Xu
Price
42.00 $
Page No. 393
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 51 – No. 5/2013 (393-400)
Pharmacokinetics and efficacy of ropivacaine in Chinese patients following intra-articular administration
Saizhen Chen1,2, Zhongyi Chen2, Yinxiu Jin3, Ziyou Tian1, Xuezheng Lin1, Mengyong Zhu1, Shanshan Xu1, Jiamiao Lin1 and Lijun Xu1
1Taizhou Central Hospital, 2Taizhou Hospital, and 3Taizhou Vocational & Technical College, Taizhou, Zhejiang, China
Objective: The purpose of the present study was to investigate the pharmacokinetics and efficacy of ropivacaine in Chinese patients by intra-articular administration after arthroscopic knee surgery, in order to assess the safety and efficacy. Patients and methods: 21 ASA I-II patients received a single-dose of ropivacaine 150 mg in a 20 ml intra-articular injection at the end of surgery. Plasma samples were collected prior to and after ropivacaine administration. Plasma concentrations of ropivacaine were measured by HPLC. Pharmacokinetic parameters were calculated using noncompartmental analysis. Population pharmacokinetic modeling was performed to yield estimates of clearance, volume of distribution, and absorption rate constant. An analysis of covariates on the pharmacokinetic parameters was also carried out. Pain assessments were made using a verbal rating scale at intervals of 2, 4, 8, 12, 24, 36, 48 and 72 hours after surgery. Results: The results show that the peak plasma concentrations occurred at an average of 0.93 ± 0.56 h (0.25 – 2 h), with a mean of 0.91 ± 0.4 mg/l (range 0.35 – 1.54 mg/l). The peak plasma concentrations and the times to reach the peak plasma concentration exhibited a marked variability among the subjects. All concentrations were well below the estimated toxic threshold (2.2 mg/l). No patient experienced adverse events that may have been related to ropivacaine administration. The intra-articular use of ropivacaine provided excellent control of pain after knee arthroscopy. Conclusion: Ropivacaine 150 mg provided satisfactory postoperative pain relief and can be safely administered by intraarticular injection in Chinese patients after arthroscopic knee surgery and the pharmacokinetic profiles of ropivacaine exhibited marked variability among the subjects. The high variability of pharmacokinetic profiles in this study may be caused by gender and body weight.Correspondence to:
Saizhen Chen
Department of Pharmacy
Taizhou Central Hospital
Taizhou, Zhejiang 318000, China
Email: [email protected]
Original
Lack of a relationship between the serum concentration of aminoglycosides and ototoxicity in neonates
Rianto Setiabudy, Ronny Suwento, Lily Rundjan, Fikry H. Yasin, Melva Louisa, Adisti Dwijayanti and Ernawati Simanjuntak
Price
42.00 $
Page No. 401
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 51 – No. 5/2013 (401-406)
Lack of a relationship between the serum concentration of aminoglycosides and ototoxicity in neonates
Rianto Setiabudy1, Ronny Suwento2, Lily Rundjan3, Fikry H. Yasin2, Melva Louisa1, Adisti Dwijayanti4 and Ernawati Simanjuntak5
1Department of Pharmacology and Therapeutics, 2Department of Ear, Nose, and Throat, Ciptomangunkusumo Hospital, Faculty of Medicine, 3Neonatology Division, Cipto Mangunkusumo Hospital, 4Department of Medical Pharmacy and 5Jakarta Provincial Health Laboratory, Jakarta, Indonesia
Introduction: Gentamicin and the other aminoglycosides are toxic antibiotics, but they are urgently needed to treat newborns with neonatal sepsis. Aminoglycosides are well known for their nephrotoxicity and ototoxicity. The aminoglycoside dosage currently applied in Indonesia is derived from studies done in Caucasian populations. The safety and efficacy of this dosage regimen, however, has never been evaluated to date. The pharmacokinetic profile of drugs may vary between populations and this may be influenced by genetic factors, lifestyle, drug interactions, etc. The detection of aminoglycoside toxicity in newborns is usually problematic. The present study aims to know the proportion of ototoxicity in newborns in the Cipto Mangunkusumo Hospital treated with gentamicin or amikacin in relation to their trough serum concentration. Methods: The serum level of gentamicin and amikacin were quantified using Liquid Chromatography Tandem Mass Spectrometry (LC-MSMS), and is assumed to be safe if the trough serum concentrations are < 2 mcg/ml and effective if it is between 5 – 12 mcg/ml. For amikacin the desired trough serum concentrations are < 10 mcg/ml and the peak is between 20 – 30 mcg/ml. The hearing function was assessed by Distortion Product Otoacoustic Emission (DPOAE) instrument. This study is registered with the www.clinicaltrials.gov NCT01624324. Conclusion: Our study indicated that there was no relationship between aminoglycosides serum trough concentration and ototoxicity in neonates with neonatal sepsis.Correspondence to:
Rianto Setiabudy, MD, PhD
Departement Farmakologi dan Terapeutik
Fakultas Kedokteran Universitas Indonesia
Jl. Salemba 6, Jakarta Pusat, Jakarta, 10430, Indonesia
Email: [email protected]
Original
Initial dosage regimens of vancomycin for Chinese adult patients based on population pharmacokinetic analysis
Chenhui Deng, Taotao Liu, Tianyan Zhou, Hua Lu, Daohai Cheng, Xiaobing Zhong and Wei Lu
Price
42.00 $
Page No. 407
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 51 – No. 5/2013 (407-415)
Initial dosage regimens of vancomycin for Chinese adult patients based on population pharmacokinetic analysis
Chenhui Deng1,2, Taotao Liu3, Tianyan Zhou1,2, Hua Lu3, Daohai Cheng3, Xiaobing Zhong3 and Wei Lu1,2
1State Key Laboratory of Natural and Biomimetic Drugs, 2School of Pharmaceutical Sciences, Peking University, Beijing, and 3The First Affiliated Hospital of Guangxi Medical University, Guangxi, China
Objective: To build a population pharmacokinetic model for Chinese adult patients and develop initial dosage regimens for patients with different degrees of renal function to achieve target steady-state trough concentrations in the range of 10 – 15 and 15 – 20 mg/l. Method: Data on serum vancomycin concentration was collected from a retrospective study including 72 Chinese adult patients. NONMEM was used to build the population pharmacokinetic model, and a one-compartment model was chosen to describe the vancomycin concentration-time profile. Internal evaluation by bootstrap and visual predictive check (VPC) was performed to evaluate the robustness and prediction of the final model. Monte Carlo simulations were conducted to develop initial dosage regimens to achieve target trough concentrations. Results: A one-compartment model was built with creatinine clearance (CLcr) as the key covariate influencing drug clearance. The estimated drug clearance for patients with normal renal function (CLcr ≥ 80 ml/min) was 4.90 l/h, and 0.0654 × CLcr if CLcr was < 80 ml/min. The apparent volume of the central compartment was 47.76 l and no covariate was found to affect it. The results of bootstrap analysis were in agreement with the original parameters of the final model, and VPC of the final model demonstrated good predictability. Initial dosage regimens were developed based on the simulations of the population pharmacokinetic model. Conclusion: A one-compartment model fitted the retrospective data and CLcr had a significant effect on drug clearance. Initial dosage regimens for vancomycin were proposed to provide some help to individual therapy for Chinese adult patients with different renal functions.Correspondence to:
Dr. Wei Lu
School of Pharmaceutical Sciences
Peking University, Beijing 100191, China
Email: [email protected]
Original
Frequency of hospitalizations prior to and after conversion to a rebate pharmaceutical in depression patients in Germany
Karel Kostev, Uwe May, Christian Ott, Marc Paul, Klaus Schetschok, Malte Tingelhoff, Carolin Claus and Lilia Waehlert
Price
42.00 $
Page No. 416
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 51 – No. 5/2013 (416-422)
Frequency of hospitalizations prior to and after conversion to a rebate pharmaceutical in depression patients in Germany
Karel Kostev1*, Uwe May2*, Christian Ott2, Marc Paul2, Klaus Schetschok2, Malte Tingelhoff2, Carolin Claus2 and Lilia Waehlert2
1IMS Health, Frankfurt am Main, and 2Hochschule Fresenius, FB Wirtschaft und Medien, FG Gesundheitsökonomie, Idstein, Germany
*both authors contributed equally to the manuscript
Background: The aim of this study was to investigate the frequency of hospitalization in depression patients with and without conversion to a rebate pharmaceutical and to show the negative consequences of rebate contracts on the health of patients with depression. Methods: This retrospective study was performed using two databases that included data on ~ 10 millions patients gathered between July 2009 and June 2012. This study included adults (> 18 years) on an antidepressive drug therapy who had statutory health insurance with rebate contracts on antidepressive pharmaceuticals. Results: In total, 47,968 patients on an antidepressive drug therapy were included in the persistence analysis using the IMS Disease Analyzer database. Of those, 26,651 patients were converted to a rebate product whereas 21,317 patients continued with the initial pharmaceutical product. After adjusting for the majority of demographic and clinical variables, the risk of hospitalization was 57% higher in patients who switched to a rebate pharmaceutical in comparison to patients who did not. When projected to the national level, this was found to equal an additional 34,157 patients hospitalized due to conversion to a rebate pharmaceutical resulting in direct inpatient costs amounting to 363.8 million EUR per year in Germany. Conclusions: Despite some limitations, this analysis presents a clear association between the initiation of rebate contracts and a negative impact on the health of patients on an antidepressive drug therapy.Correspondence to:
Dr. Karel Kostev
Senior Research Adviser
IMS HEALTH – Epidemiology
Darmstädter Landstraße 108
60598 Frankfurt am Main, Germany
Email: [email protected]
Original
Pharmacokinetics of single and multiple oral doses of arbidol in healthy Chinese volunteers
Yaxin Sun, Xiaojing He, Feng Qiu, Xu Zhu, Mingming Zhao, Jesse Li-Ling, Xianying Su and Limei Zhao
Price
42.00 $
Page No. 423
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 51 – No. 5/2013 (423-432)
Pharmacokinetics of single and multiple oral doses of arbidol in healthy Chinese volunteers
Yaxin Sun1, Xiaojing He1, Feng Qiu1, Xu Zhu1, Mingming Zhao1, Jesse Li-Ling2,3, Xianying Su4 and Limei Zhao1
1Department of Pharmacy, Shengjing Hospital of China Medical University, 2Sino-Dutch Biomedical and Information Engineering School, Northeastern University, Shenyang, 3Institute of Medical Genetics, School of Life Science & Key Laboratory for Bio-resources and Eco-environment of the Ministry of Education, Sichuan University, Chengdu, and 4Northeast Pharmaceutical Science & Technology Development Co., Ltd., Shenyang, China
Background: Arbidol is licensed in Russia and China for prophylaxis and treatment of influenza A and B. This study was to assess the pharmacokinetics of single and multiple doses of arbidol in healthy Chinese volunteers. Methods: This was a single-center, open-label, two-phase study conducted in 12 subjects. In singledose phase, subjects were randomized to receive single doses of 0.2, 0.4 and 0.8 g of arbidol in a crossover design with a 7-day washout period between administration. In the multiple-dose phase, subjects received 0.2 g 3 times a day for 7 days. Serial blood samples were collected at predefined time points. Plasma concentrations were determined with a validated HPLC method. Safety assessments were conducted throughout the study. Results: After administration of single doses of 0.2, 0.4 and 0.8 g, geometric mean estimates for arbidol Cmax were 0.70, 1.24, and 2.16 mg/l and the mean of AUClast were 3.27, 5.81 and 12.72 mg×h/l, respectively. The AUClast and Cmax showed dose proportionality. After administration of multiple doses, the mean of Cmax,ss of arbidol was 0.41 mg/l and the mean accumulation ratio is ~ 1.12. Compared with single-dose phase, arbidol exhibited lower Cmax and prolonged plasma concentration profiles. Conclusions: In healthy Chinese subjects, single dosing of arbidol resulted in linear plasma pharmacokinetics. Arbidol exhibited little accumulation with repeated administration. Compared with single doses, multiple oral doses showed somewhat different pharmacokinetics and tissue distribution patterns. Sex did not appear to affect the pharmacokinetic properties of arbidol.Correspondence to:
Professor Limei Zhao, PhD
Department of Pharmacy
Shengjing Hospital of China Medical University
Shenyang, China
Email: [email protected]
Original
Current situation of clinical trials in Beijing and Shanghai, China
Yoshitoku Yoshida, Di Xue, Yasuko Yoshida, Yumei Zhang, Defu Ma, Yuzo Sato and Peiyu Wang
Price
42.00 $
Page No. 433
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 51 – No. 5/2013 (433-440)
Current situation of clinical trials in Beijing and Shanghai, China
Yoshitoku Yoshida1, Di Xue2, Yasuko Yoshida3, Yumei Zhang4, Defu Ma4, Yuzo Sato5 and Peiyu Wang4
1Young Leaders’ Program of Health Care Administration, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan, 2School of Public Health, Fudan University, Shanghai, China, 3Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi, Japan, 4School of Public Health, Peking University, Beijing, China and 5Department of Health Science, Aichi Gakuin University, Nisshin City, Aichi, Japan
Objective: Global clinical trials are important because they facilitate rapid delivery of new and effective drugs to patients Assessment of the current situation of clinical trials conducted in Asia is critical for improving performance of global clinical trials. However, review reports from China or other Asian countries are not yet available. Therefore, the purpose of this research was to investigate the current quality of clinical trials conducted in Shanghai, as well as Beijing. Methods: Questionnaires were distributed to medical doctors attending institutes in Beijing and Shanghai in which clinical trials have been conducted. These questionnaires were delivered and collected from both areas by the Peking University research team of Beijing and the Fudan University research team of Shanghai respectively. Analysis and evaluation were conducted by research teams from both China and Japan. Results: Subjects were randomly selected by the respective research team. A total of 145 questionnaires in Beijing and 162 in Shanghai were administered: all 307 questionnaires were completed. In total, 57.2% and 74.5% of respondents from Beijing and Shanghai, respectively, reported participation in audits and inspections on an annual basis conducted by their own institute. A total of 49.2% and 56.0% of respondents from Beijing and Shanghai, respectively, reported that they received reports after the audits and inspections by an institute. 23.5% and 37.7% of respondents from Beijing and Shanghai, respectively, reported participation in audits conducted annually by external authorities. A total of 18.9% and 29.5% of respondents from Beijing and Shanghai, respectively, reported that they received reports after the audits and inspections by an external authority. Conclusions: Our research suggests that clinical trials in Shanghai, as well as in Beijing, are conducted vigorously and appropriately monitored by audits and inspections conducted by concerned institutes and/or by an external authority.Correspondence to:
Yoshitoku Yoshida, PhD
Graduate School of Medicine, Nagoya University
65 Tsurumaicho, Showa-ku
Nagoya, Aichi 466-8550, Japan
Email: [email protected]
Case Report
Pregabalin abuse after past substanceseeking behavior
Georgios Papazisis, Georgios Garyfallos, Chrysanthi Sardeli and Dimitrios Kouvelas
Price
42.00 $
Page No. 441
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 51 – No. 5/2013 (441-442)
Pregabalin abuse after past substanceseeking behavior
Georgios Papazisis1, Georgios Garyfallos2, Chrysanthi Sardeli1 and Dimitrios Kouvelas1
1Department of Pharmacology and Clinical Pharmacology and 22nd Department of Psychiatry, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
Pregabalin is a prescription drug, structurally related to the neurotransmitter GABA. Following the rapidly increasing use of pregabalin, data signaling its abuse liability have been published recently. We report a case of a 19-year-old man with a history of cannabis and alcohol-seeking behavior that showed similar drug-seeking behavior with pregabalin. This report highlights the potential for abuse of pregabalin in patients with a history of substance-seeking behavior. Considering that the drug has recently been proposed as a treatment for alcohol- and benzodiazepine-dependence a better clarification of its abuse potential is essential.Correspondence to:
Georgios Papazisis, MD, PhD
Department of Pharmacology and Clinical Pharmacology
School of Medicine
Aristotle University of Thessaloniki
Thessaloniki, Greece
Email: [email protected]
