Volume 53, No. 10/2015(October)
The online-version will be updated before the print-version of this Journal is published. Upon request we will send the password and user name by e-mail. The online-service is only available for subscribers of the print-version, if proof of purchase is submitted.
The use of the online-version will be charged with an extra fee (additional to the subscription of the print-version). The service can be used until December 31st of the year of subscription.
|
| Price of the complete print-issue: 30.00$ |
Add to Cart
|
Viewpoint
Good publication practices in clinical pharmacology: transparency, evidence-based medicine and the 7-D assessment
Barry G. Woodcock and Veronika Luger
Page No. 799
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 10/2015 (799-802)
Good publication practices in clinical pharmacology: transparency, evidence-based medicine and the 7-D assessment*
Barry G. Woodcock and Veronika Luger
Dustri Medical Science Publications, Munich-Oberhaching, Germany
Transparency and evidence-based medicine are cornerstones of good publication practices (GPP), and concern publishers, editors, research investigator, and reviewers alike. Methods for implementing these principles within the framework of GPP are described. The main aspects include obtaining a Manuscript Agreement Contract, a Statement on Transparency of Authorship and a Declaration of Conflicts of Interest from the authors. Assessing whether a manuscript meets the requirements of EBM is demonstrated using the “7-D assessment”. The main purpose of this tool is to established that the (1) right Design, (2) right Diagnosis, (3) right Drug molecule, (4) right Dosage, (5) right Data, (6) right Deductions, and (7) right Documentation have been implemented in order to meet the objectives of the investigation. If the findings from any one of these assessments is questionable, the compliance of the research with EBM principles will be weakened and the reviewers and editors will make recommendations to the publisher accordingly. The guidelines described will help to provide a fair and transparent process of scientific publication and foster the freedom of clinical pharmacological research.
*This text is based on an internal report outlining how the principles of evidence- based medicine can be incorporated into good publication practices: Publication of research findings in medicine and the Editorial Policy of the International Journal of Clinical Pharmacology and Therapeutics by B.G. Woodcock and V. Luger. Dustri Medical Science Publications. Dustri-Verlag Dr. Karl Feistle GmbH & Co. KG, Munich-Oberhaching, Germany and Dustri- Verlag Inc., Rockledge, FL, USA, www.dustri. com, July 2015.Correspondence to:
BG Woodcock
PO 20 02 32, 63308 Rödermark, Germany
Email: [email protected]
Original Research
Comparative effectiveness and tolerability of esomeprazole and omeprazole in gastro-esophageal reflux disease: A systematic review and meta-analysis
Qian Qi, Rugang Wang, Lin Liu, Feng Zhao, and Sheng Wang
Price
42.00 $
Page No. 803
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 10/2015 (803-810)
Comparative effectiveness and tolerability of esomeprazole and omeprazole in gastro-esophageal reflux disease: A systematic review and meta-analysis*
Qian Qi*1, Rugang Wang*2, Lin Liu3, Feng Zhao4, and Sheng Wang5
1Department of Gastroenterology, 2Department of Laboratory Medicine, 3Department of Transfusion Medicine, 4Institute of Gastroenterology, Linzi District People’s Hospital, Binzhou Medical University, and 4Medical Intensive Care Unit, Qilu Shihua Central Hospital, Weifang Medical University, Zibo City, Shandong Province, China
This study aims to evaluate the effectiveness and tolerability of esomeprazole and omeprazole in patients with gastroesophageal reflux disease (GERD). Electronic searches on PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov databases were carried out for reports up to February 28, 2015. Ten eligible studies from 8 articles were found that enrolled a total of 10,286 patients for meta-analysis. These results revealed a significant difference between esomeprazole vs. omeprazole (RR = 1.06, 95% CI [1.01, 1.10], I2 = 72%, p = 0.01) by subgroup according to dosage by random effects model, and a significant difference between esomeprazole 40 mg vs. omeprazole 20 mg (RR = 1.07, 95% CI [1.004, 1.14], I2 = 78%, p = 0.04) based on healing rate as determined by endoscopy, using a random effects model. A significant difference between esomeprazole 20 mg and omeprazole 40 mg (RR = 0.68, 95% CI [0.47, 0.97], I2 = not applicable, p = 0.03) was also found in comparing relief of symptoms by random effects model. There were no significant differences in outcomes between other subgroups, including tolerability. Based on these results, a high dose of esomeprazole is recommended for GERD treatment and control in adults.
*Co-authorCorrespondence to:
Sheng Wang, MD
Institute of Gastroenterology, Linzi District People’s Hospital
Binzhou Medical University, No.139,
Huangong Road, Linzi District, Zibo City
255400, Shandong Province, China
Email: [email protected]
Original Research
Once-daily dosing of levocabastine has comparable efficacy to twice-daily dosing in the treatment of allergic rhinitis assessed in an allergen challenge chamber
Robert D. Murdoch, Philippe Bareille, Diane Ignar, Stephen Mark, Sam R. Miller, Ashutosh Gupta, Anne-Marie Salapatek, and Piyush Patel
Price
42.00 $
Page No. 811
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 10/2015 (811-818)
Once-daily dosing of levocabastine has comparable efficacy to twice-daily dosing in the treatment of allergic rhinitis assessed in an allergen challenge chamber
Robert D. Murdoch1, Philippe Bareille1, Diane Ignar2, Stephen Mark3, Sam R. Miller1, Ashutosh Gupta4, Anne-Marie Salapatek5, and Piyush Patel5
1GlaxoSmithKline, Stevenage, UK, 2GlaxoSmithKline, Research Triangle Park, NC, USA, 3GlaxoSmithKline, Mississauga, ON, Canada, 4Quantitative Sciences India, GlaxoSmithKline, Bangalore, India, and 5Inflamax Research Incorporated, Mississauga, Ontario, Canada
Objectives: To test the hypothesis that intranasal levocabastine (LEVO) may provide benefits as a oncedaily treatment in allergic rhinitis (AR), this non-inferiority study compared the effect at steady state of once- and twice-daily dosing with LEVO on allergen-induced nasal symptoms in AR patients. Methods: This was a randomized, double-blind, three-way cross over study evaluating the effects of repeat doses of LEVO 200 μg once-daily, LEVO 200 μg twice-daily (total dose 400 μg) and placebo, all via intranasal spray, in 78 AR patients. The primary endpoint was weighted mean total nasal symptom score (TNSS) during a 4-hour allergen exposure in the Environmental Exposure Chamber measured at trough pharmacokinetic levels either 12 (LEVO twice-daily) or 24 (LEVO once-daily) hours post-dose. Results: After 7 days dosing, the difference in weighted mean TNSS (0 – 4 hours) following LEVO once-daily versus twice-daily was 0.23 units (95% CI –0.36, 0.82), demonstrating noninferiority between the two LEVO dosing regimens by meeting the pre-specified criterion of an upper limit of 95% CI < 1.0. Both dosing regimens of LEVO resulted in a statistically significant reduction in mean TNSS compared with placebo (adjusted mean difference from placebo: LEVO oncedaily: –1.12 (95% CI –1.71, –0.53); LEVO twice-daily: –1.35 (–1.94, –0.76)), meeting the pre-specified criterion for superiority (upper limit of 95% CI < 0). All treatments were well-tolerated. Conclusions: The results of this study support the hypothesis that at steady state LEVO 200 μg taken once-daily provides similar benefit to LEVO 200 μg dosed twice-daily.Correspondence to:
Dr. Robert D. Murdoch
GlaxoSmithKline
Gunnels Wood Road, Stevenage Herts, SG1 2NY, UK
Email: [email protected]
Appendix
Potentially inappropriate medication use at ambulatory care visits by elderly patients covered by National Health Insurance in Korea
Dong-Sook Kim, Soonim Huh, and Sukhyang Lee
Price
42.00 $
Page No. 819
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 10/2015 (819-827)
Potentially inappropriate medication use at ambulatory care visits by elderly patients covered by National Health Insurance in Korea
Dong-Sook Kim1, Soonim Huh2, and Sukhyang Lee3
1Research Team, Health Insurance Review & Assessment Service, 2Department of Public Administration, University of Seoul, Seoul, and 3College of Pharmacy, Ajou University, Suwon, Korea
Appendix free of charge.Correspondence to:
Soonim Huh, Ph.D.
Department of Public Administration
University of Seoul, Seoul 130-743, Korea
Email: [email protected]
Original Research
Ferulic acid alleviates Aβ25–35- and lipopolysaccharide-induced PC12 cellular damage: a potential role in Alzheimer’s disease by PDE inhibition
Hao Huang, Zeng-Chun Ma, Yu-Guang Wang, Qian Hong, Hong-Ling Tan, Cheng-Rong Xiao, Qian-De Liang, Xiang-Lin Tang, and Yue Gao
Price
42.00 $
Page No. 828
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 10/2015 (828-837)
Ferulic acid alleviates Aβ25–35- and lipopolysaccharide-induced PC12 cellular damage: a potential role in Alzheimer’s disease by PDE inhibition
Hao Huang1,2, Zeng-Chun Ma2, Yu-Guang Wang2, Qian Hong3, Hong-Ling Tan2, Cheng-Rong Xiao2, Qian-De Liang2, Xiang-Lin Tang2, and Yue Gao2
1College of Life Science and Bioengineering, Beijing University of Technology, 2Beijing Institute of Radiation Medicine, Beijing, and 3No. 97 Hospital of CPLA, Xuzhou, China
Objective: Phosphodiesterase (PDE) plays an important role in the pathogenesis of Alzheimer’s disease (AD). Ferulic acid (FA) has a therapeutic benefit in the treatment of AD. We investigated whether this therapeutic effect is based on the modulation of the PDE/cyclic adenosine monophosphate (cAMP) pathway. In the present study, we investigated whether FA could abrogate Aβ25–35- and lipopolysaccharide-induced cellular damage. Materials and methods: Cell viability, superoxide production, and the levels of inflammatory factors were investigated. We further investigated the intracellular levels of cAMP and Ca2+, both of which are associated with PDE activity. Furthermore, molecular docking was used to identify the binding mode between phosphodiesterase 4B2 (PDE4B2) and FA. Results: Pretreatment with FA significantly maintained cell viability, increased the levels of superoxide dismutase, and inhibited production of TNF-α and IL-1β induced by Aβ25–35. Moreover, pretreatment with FA increased the intracellular levels of cAMP and decreased the intracellular levels of Ca2+. The docking results also showed that FA has the potential to inhibit PDE4B2 activity. Conclusions: Taken together, our results suggested that one of the therapeutic effects of FA on AD was potentially mediated by modulating the PDE/cAMP pathway.Correspondence to:
Dr. Yue Gao, Zeng-Cun Ma
Beijing Institute of Radiation Medicine
27 Tai-Ping Road, Beijing, 100850, PR China
Email: [email protected]
Original Research
Absorption, distribution, metabolism, and excretion of [14C]-labeled naloxegol in healthy subjects
Khanh Bui, Fahua She, Michael Hutchison, Åsa Brunnström, and Mark Sostek
Page No. 838
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 10/2015 (838-846)
Absorption, distribution, metabolism, and excretion of [14C]-labeled naloxegol in healthy subjects
Khanh Bui1, Fahua She2, Michael Hutchison3, Åsa Brunnström4, and Mark Sostek2
1AstraZeneca Pharmaceuticals, Wilmington, DE, USA, 2AstraZeneca Pharmaceuticals, Gaithersburg, MD, USA, 3AstraZeneca UK Ltd., Cheshire, UK, and 4AstraZeneca Pharmaceuticals, Södertälje, Sweden
Objective: To characterize the absorption, distribution, metabolism, and excretion of naloxegol, a PEGylated derivative of the µ-opioid antagonist naloxone, in healthy male subjects. Materials and methods: [14C]-Labeled naloxegol (27 mg, 3.43 MBq) was administered as an oral solution to 6 fasted subjects. Blood, fecal, and urine samples were collected predose and at various intervals postdose. Naloxegol and its metabolites were quantified or identified by liquid chromatography with radiometric or mass spectrometric detection. Pharmacokinetic parameters were calculated for each subject, and metabolite identification was performed by liquid chromatography with parallel radioactivity measurement and mass spectrometry. Results: Naloxegol was rapidly absorbed, with a maximum plasma concentration (geometric mean) of 51 ng/mL reached before 2 hours after dosing. A second peak in the observed naloxegol and [14C] plasma concentration-time profiles was observed at ~ 3 hours and was likely due to enterohepatic recycling of parent naloxegol. Distribution to red blood cells was negligible. Metabolism of [14C]-naloxegol was rapid and extensive and occurred via demethylation and oxidation, dealkylation, and shortening of the polyethylene glycol chain. Mean cumulative recovery of radioactivity was 84.2% of the total dose, with ~ 68.9% recovered within 96 hours of dosing. Fecal excretion was the predominant route of elimination, with mean recoveries of total radioactivity in feces and urine of 67.7% and 16.0%, respectively. Unchanged naloxegol accounted for ~ 1/4 of the radioactivity recovered in feces. Conclusions: Naloxegol was rapidly absorbed and cleared via metabolism, with predominantly fecal excretion of parent and metabolites.Correspondence to:
Mark Sostek, MD
Global Medicines Development
AstraZeneca Pharmaceuticals, AstraZeneca LP
One MedImmune Way, 200 ORD - 1107G
Gaithersburg, MD 20878, USA
Email: [email protected]
Original Research
Pharmacokinetics of fingolimod and metabolites in subjects with severe renal impairment: An open-label, single-dose, parallel-group study
Olivier J. David, Maxwell Pryce, Karin Meiser, Franck Picard, Corinne Emotte, Zhanna Kobalava, Valentin Moiseev, and Robert Schmouder
Price
42.00 $
Page No. 847
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 10/2015 (847-854)
Pharmacokinetics of fingolimod and metabolites in subjects with severe renal impairment: An open-label, single-dose, parallel-group study
Olivier J. David1, Maxwell Pryce1, Karin Meiser1, Franck Picard1, Corinne Emotte1, Zhanna Kobalava2, Valentin Moiseev2, and Robert Schmouder3
1Novartis Pharma AG, Basel, Switzerland, 2Peoples’ Friendship University of Russia, Center of Applied Clinical Pharmacology, Moscow, Russia, and 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
Objective: This study assessed the pharmacokinetics and tolerability of fingolimod and its metabolites in severe renal impairment and healthy subjects. Methods: In this single-dose, open-label study, 9 severe renal impairment subjects and 9 demographically matched healthy subjects were included. Each subject received a single oral dose of fingolimod 1.25 mg, and their blood and urine samples were assessed. The pharmacokinetics of fingolimod and its metabolites, fingolimod-phosphate (active metabolite, fingolimod-P), M2, and M3, were compared in both groups. Safety and tolerability were also assessed. Results: In severe renal impairment subjects, mean ± standard deviation values of Cmax (ng/mL) of fingolimod and fingolimod-P were 0.878 ± 0.256 and 1.13 ± 0.293 vs. 0.653 ± 0.138 and 0.904 ± 0.229 in healthy subjects, respectively. The overall drug exposures (AUCinf (ng×h/mL)) for fingolimod and fingolimod-P were 131 ± 90.7 and 75.5 ± 33.6 in severe renal impairment subjects vs. 82.3 ± 36.9 and 65.9 ± 30.6 in healthy subjects, respectively. t1/2 (hours) for fingolimod and fingolimod-P was comparable in severe renal impairment subjects (94 ± 53 and 95 ± 50) and healthy subjects (85 ± 25 and 101 ± 46). All adverse events were as expected for fingolimod 1.25 mg. Conclusions: The exposure to fingolimod and fingolimod-P was moderately increased (90% CI, 0.94 – 2.18) in severe renal impairment subjects, while half-lives and protein binding were similar to those in healthy subjects. Given that these changes are not clinically meaningful, fingolimod dose adjustment is considered unnecessary in patients with mild, moderate, or severe renal impairment.Correspondence to:
Olivier J. David
Novartis Pharma AG, Pharmacometrics
Novartis Campus, WSJ-27.6.11, CH-4056 Basel, Switzerland
Email: [email protected]
Original Research
Pharmacokinetic and pharmacodynamic interaction of siponimod (BAF312) and propranolol in healthy subjects
Shibadas Biswal, Florine Polus, Parsar Pal, Uday Kiran Veldandi, Thomas C. Marbury, Robert Perry, and Eric Legangneux
Price
42.00 $
Page No. 855
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 10/2015 (855-865)
Pharmacokinetic and pharmacodynamic interaction of siponimod (BAF312) and propranolol in healthy subjects
Shibadas Biswal1, Florine Polus2, Parsar Pal1, Uday Kiran Veldandi1, Thomas C. Marbury3, Robert Perry4, and Eric Legangneux2
1Novartis Healthcare Pvt. Ltd., Hyderabad, India, 2Novartis Pharma AG, Basel, Switzerland, 3Orlando Clinical Research Center, Orlando, and 4Elite Research Institute, Miami, FL, USA
Objective: To evaluate the cardiac and pulmonary effects of siponimod (BAF312) and propranolol co-administration in healthy subjects. Methods: Healthy subjects (n = 76) were randomized in a doubleblind manner to receive propranolol at siponimod steady state (group A), siponimod at propranolol steady state (group B), placebo (group C) and propranolol (group D). Pharmacodynamic evaluations included maximum change from baseline in time-matched hourly average heart rate (Emax HR) and mean arterial blood pressure (Emax MABP) over 24 hours postdose, change from baseline in PR intervals, cardiac rhythm, and forced expiratory volume in 1 second (FEV1). Pharmacokinetic and safety parameters were also assessed. Results: Siponimod and propranolol when administered alone resulted in similar HR decrease at steady state. Compared to propranolol alone, the combination at steady state had an additional 6.21 bpm (95%CI: 2.32, 10.11) decrease of mean EmaxHR, a decrease of 5.04 bpm (0.52, 9.56) for group A and 7.39 bpm (2.87, 11.90) for group B. A minor decrease in MABP and a trend towards PR interval increase were noted with co-administration treatment vs. propranolol alone. There were no episodes of second-degree atrioventricular blocks or sinus pauses > 3 seconds. Baseline-corrected FEV1 was reduced by –0.07 L (95% CI: –0.17, 0.03) for group A and –0.05 L (-0.15, 0.05) for group B vs. propranolol alone. There were no cardiovascular adverse events during coadministration treatment. Conclusions: Coadministration of siponimod and propranolol was well tolerated. Bradyarrhythmic effects were less pronounced when propranolol was added to siponimod steady-state therapy compared with siponimod addition to propranolol.Correspondence to:
Eric Legangneux, MD
Head Profiling Neuroscience, Translational Medicine
Novartis Institutes for BioMedical Research
WSJ 386.12.48.56, 4002 Basel, Switzerland
Email: [email protected]
Original Research
Lack of effect of favipiravir, a novel antiviral agent, on QT interval in healthy Japanese adults
Yuji Kumagai, Yuji Murakawa, Tomoko Hasunuma, Masako Aso, Wakako Yuji, Tsutomu Sakurai, Masahiko Noto, Tetsuya Oe, and Akiko Kaneko
Price
42.00 $
Page No. 866
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 10/2015 (866-874)
Lack of effect of favipiravir, a novel antiviral agent, on QT interval in healthy Japanese adults
Yuji Kumagai1, Yuji Murakawa2, Tomoko Hasunuma3, Masako Aso1, Wakako Yuji4, Tsutomu Sakurai5, Masahiko Noto5, Tetsuya Oe5, and Akiko Kaneko6
1Clinical Trial Center, Kitasato University Hospital, Kanagawa, 2Fourth Department of Internal Medicine, Mizonokuchi Hospital, Teikyo University School of Medicine, Kanagawa, 3Clinical Pharmacology Center, Oita University Hospital, Oita, 4Biomedical Research Center, Kitasato Institute Hospital, Tokyo, 5Clinical Research Department, Toyama Chemical Co., Ltd., Tokyo, and 6Data Science and Administration Department, Toyama Chemical Co., Ltd., Tokyo, Japan
Objective: A thorough QT study of favipiravir, a novel antiviral agent, was conducted using a randomized, doubleblind, 4-group, 4-period crossover, placeboand positive-controlled (open-label moxifloxacin) design. Materials and methods: 56 healthy Japanese adults of both sexes received single oral doses of favipiravir 1,200 and 2,400 mg (Avigan® Tablets, Toyama Chemical Co., Ltd.), moxifloxacin 400 mg, and a placebo. QT intervals after these treatments were measured under blinded conditions. The primary endpoint was the time-matched, placebo-adjusted change in corrected QT intervals using the Fridericia method (QTcF) from predose for favipiravir or moxifloxacin (ΔΔQTcF). Results: Lower bounds of the two-sided 90% confidence interval of ΔΔQTcF values for moxifloxacin exceeded 3 msec at all time points, and the maximum value was 14.0 (11.8 – 16.1, 90% confidence interval) msec at 3 hours after administration. Similarly, maximum ΔΔQTcF values for favipiravir were 0.833 (–1.33 – 3.00) msec at 3 hours after administration of 1,200 mg, and 0.500 (–1.88 –2.88) msec at 6 hours after administration of 2,400 mg. Calculation of the sample size using the ΔΔQTcF value of moxifloxacin indicated that 25 subjects would be sufficient for detection at a power of 90% or higher, which meets the criteria for assuring assay sensitivity. Conclusions: It is possible to use a smaller number of subjects in thorough QT studies in Japan than in Europe and the US utilizing moxifloxacin as a positive control. There were no detectable effects of favipiravir on the QT/QTc interval.Correspondence to:
Yuji Kumagai, MD, PhD
Clinical Trial Center, Kitasato University Hospital
15-1 Kitazato 1-chome, Minami-ku,
Sagamihara, Kanagawa, 252-0375 Japan
Email: [email protected]
Original Research
Pharmacokinetics of trantinterol and its metabolite in healthy elderly and young subjects
Jie Huang, Qi Pei, Hongyi Tan, Hong Yuan, Youli Lu, Gangyi Liu, Zhijun Huang, and Guoping Yang
Price
42.00 $
Page No. 875
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 10/2015 (875-882)
Pharmacokinetics of trantinterol and its metabolite in healthy elderly and young subjects
Jie Huang1, Qi Pei1, Hongyi Tan1, Hong Yuan1, Youli Lu2, Gangyi Liu2, Zhijun Huang*1, and Guoping Yang*1
1Center of Clinical Pharmacology, Third Xiangya Hospital, Central South University, Changsha, Hunan and 2Drug Clinical Research Centre of Shanghai Xuhui Central Hospital, Shanghai, China
Objective: The aim of this study was to investigate and compare the pharmacokinetics of trantinterol and its active amphoteric carboxylic acid metabolite (1-carbonyl trantinterol) between the healthy elderly and young subjects. Methods: This was a single-center, open-label, parallelgroup study completed by 22 healthy subjects (≥ 65 years (the elderly group); 18 – 45 years (the young group); 9 males and 2 females per age group) receiving single oral dose of 50 μg trantinterol tablets. Blood samples were taken at intervals up to 48 hours post-dose. Results: In both groups, maximum plasma concentration of trantinterol was researched at 0.9 hours, while the tmax of 1-carbonyl trantinterol differed slightly. Trantinterol Cmax and AUClast were higher in the elderly group than the young group, by 27% (90% CI, 0.95 – 1.69) and 77% (90% CI, 1.25 – 2.51), respectively. For 1-carbonyl trantinterol, Cmax, and AUClast were also higher, by 36% (90% CI, 1.04 – 1.78) and 71% (90% CI, 1.27 – 2.30), respectively, in the elderly group. The CL/F and V/F of trantinterol and 1-carbonyl trantinterol were significantly lower in the elderly group, while t1/2 of both did not show significant differences. CL/F of trantinterol and 1-carbonyl trantinterol were found to significantly correlate inversely with age, and positively with the baseline creatinine clearance. Conclusions: A single dose of 50 μg trantinterol was well tolerated. Significant changes in Cmax and AUC of trantinterol and 1-carbony trantinterol were seen in the elderly and may be clinically important.
*These authors contributed equally.Correspondence to:
Dr. Zhijun Huang
Center of Clinical Pharmacology
Third Xiangya Hospital, Central South University
Changsha, Hunan 410013, China
or
Prof. Guoping Yang
Center of Clinical Pharmacology
Third Xiangya Hospital, Central South University
Changsha, Hunan 410013, China
Email: [email protected] or [email protected]
Original Research
Pharmacokinetics of a telmisartan/rosuvastatin fixed-dose combination: a single-dose, randomized, open-label, 2-period crossover study in healthy Korean subjects
Dong Woo Chae, Mijeong Son, Yukyung Kim, Hankil Son, Seong Bok Jang, Jeong Min Seo, Su Youn Nam, and Kyungsoo Park
Price
42.00 $
Page No. 883
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 10/2015 (883-889)
Pharmacokinetics of a telmisartan/rosuvastatin fixed-dose combination: a single-dose, randomized, open-label, 2-period crossover study in healthy Korean subjects
Dong Woo Chae1,2, Mijeong Son1,2, Yukyung Kim1,2, Hankil Son1,2, Seong Bok Jang3, Jeong Min Seo3, Su Youn Nam3, and Kyungsoo Park1,2
1Department of Pharmacology, Yonsei University College of Medicine, 2Brain Korea 21 Plus Project for Medical Science, Yonsei University, and 3Yuhan Research Institute, Yuhan Corporation, Seoul, Republic of Korea
Objective: As hypertension and dyslipidemia are frequent comorbidities, antihypertensive drugs and lipid-lowering agents are often prescribed together for their treatment. Telmisartan and rosuvastatin are widely used together to treat hypertension and dyslipidemia. A combination formulation of these two drugs would improve patient compliance due to ease of dosing. The purpose of this study was to assess bioequivalence of single-dose administration of a newly-developed fixed-dose combination (FDC) tablet containing telmisartan/rosuvastatin 80/20 mg (test treatment) and coadministration of a telmisartan 80-mg tablet and a rosuvastatin 20-mg tablet (reference treatment) in healthy Korean male volunteers. Methods: This was a single-dose, randomized, open-label, 2-period crossover study enrolling healthy males aged 20 – 50 years with BMI between 18.5 and 25 kg/m2. Each subject received a single dose of the reference and test treatments with a 14-day washout period. Blood sampling was performed at prespecified intervals for up to 72 hours after dosing. Primary pharmacokinetic parameters were Cmax, AUClast, and AUC0–∞ of telmisartan, rosuvastatin, and N-desmethyl rosuvastatin. Bioequivalence was assessed by determining whether the 90% confidence intervals (CIs) of the geometric mean ratios (test treatment/reference treatment) of these parameters were within the standard range of 80% to 125%. Adverse events were monitored via regular interviews with the subjects and by physical examinations. Results: 60 subjects were enrolled and 55 completed the study. The 90% CIs of the geometric mean ratios of Cmax, AUClast, and AUC0–∞ were 0.9262 – 1.1498, 0.9294 – 1.0313, and 0.9312 – 1.0320 for telmisartan, 0.9041 – 1.0428, 0.9262 – 1.0085, and 0.9307 – 1.0094 for rosuvastatin, and 0.8718 – 1.0022, 0.8901 – 0.9904, and 0.8872 – 0.9767 for N-desmethyl rosuvastatin, respectively. There was no statistical difference in the incidence of adverse events (AEs) (all of which were mild or moderate) between the reference and test treatments. Conclusions: Our findings suggest that the telmisartan/rosuvastatin FDC is bioequivalent to coadministration of separate tablets, and both treatments were safe and well tolerated. Administration of this FDC tablet is expected to improve patient compliance.Correspondence to:
Kyungsoo Park, PhD, MD
Department of Pharmacology
Yonsei University College of Medicine
134 Shinchondong, Seodaemun-gu,
Seoul 120-752, Republic of Korea
Email: [email protected]
Case Report
Propofol-induced rhabdomyolysis: a case report
Zhi-Bin Zhou, Xiao-Yu Yang, Xue Zhou, Li-Jun Niu, Liang-Can Xiao, Wen-Qi Huang, and Xia Feng
Price
42.00 $
Page No. 890
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 10/2015 (890-894)
Propofol-induced rhabdomyolysis: a case report
Zhi-Bin Zhou, Xiao-Yu Yang, Xue Zhou, Li-Jun Niu, Liang-Can Xiao, Wen-Qi Huang, and Xia Feng
Department of Anesthesiology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Objective: To report a case of propofol-induced rhabdomyolysis. In this case, widespread myolysis was detected after induction of anesthesia. Case summary: A 54-year-old female patient was scheduled for a hysterectomy. Beginning shortly after the induction of anesthesia with propofol, several episodes of ventricular fibrillation occurred. Despite intensive care, the patient failed to recover. During most episodes of ventricular fibrillation, marked hyperthermia or hyperkalemia were not observed. Unexplained, widespread myolysis affecting both skeletal and cardiac muscle was observed at autopsy. Discussion: In this patient, the evidence for rhabdomyolysis is robust. Clinical characteristics are similar to those observed in propofol infusion syndrome. The absence of a body temperature over 40 °C precludes the possibility of malignant hyperthermia. Widespread rhabdomyolysis locations cannot be explained by precordial electric shocks. Propofol is the only drug used in this case that has been reported to induce rhabodomyolysis. Conclusions: Signs of propofol-induced rhabdomyolysis may be different from those of malignant hyperthermia. Even a regular induction dose of propofol for adults could possibly trigger rhabdomyolysis similar to what is observed in children diagnosed with propofol infusion syndrome. Though rare, care should still be taken when administering propofol.Correspondence to:
Xia Feng, MD, PhD
Department of Anesthesiology
First Affiliated Hospital of Sun Yat-Sen University
No.58 Zhongshan 2nd Road, Guangzhou, 510080, China
Email: [email protected]
Letter to the Editor
Efficacy of calcitriol compared to alfacalcidol for the treatment of secondary hyperparathyroidism in peritoneal dialysis patients
Sarah Bezzaoucha, Jean-Philippe Lafrance, Denis Ouimet, Vincent Pichette, Robert Bell, Caroline Lamarche, and Michel Vallée
Page No. 895
Abstract
Intern. Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 10/2015 – Letter to the editor
Efficacy of calcitriol compared to alfacalcidol for the treatment of secondary hyperparathyroidism in peritoneal dialysis patients
Sarah Bezzaoucha, Jean-Philippe Lafrance, Denis Ouimet, Vincent Pichette, Robert Bell, Caroline Lamarche, and Michel Vallée
Department of Medicine, Division of Nephrology, Hôpital Maisonneuve-Rosemont, Montreal, Canada
Correspondence to:
Michel Vallée MD, PhD
Nephrology Department of Medicine
Hôpital Maisonneuve-Rosemont
5415 Boulevard de l‘Assomption,
Montreal, H1T 2M4, Canada
Email: [email protected]
Bioavailability Section
Isotretinoin conundrum: a randomized, openlabel, crossover study in Mexico to evaluate the bioavailability and bioequivalence of three pharmaceutical preparations of isotretinoin in healthy participants
Everardo Piñeyro-Garza, Magdalena Gómez-Silva, María Elena Gamino Peña, Jonathan Palmer, and Arturo Berber
Price
42.00 $
Page No. 897
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 10/2015 (897-904)
Isotretinoin conundrum: a randomized, openlabel, crossover study in Mexico to evaluate the bioavailability and bioequivalence of three pharmaceutical preparations of isotretinoin in healthy participants
Everardo Piñeyro-Garza1, Magdalena Gómez-Silva1, María Elena Gamino Peña1, Jonathan Palmer2, and Arturo Berber3
1IPHARMA, Monterrey, Mexico, 2Clinical Pharmacology Modeling & Simulation, GlaxoSmithKline, Uxbridge, UK, and 3Formerly Local R&D, GlaxoSmithKline Mexico, Mexico City, Mexico
Objective: The oral retinoid agent isotretinoin (13-cis-retinoic acid) is approved for the treatment of severe recalcitrant cystic acne. For registrational renewal of Oratane® in Mexico (isotretinoin; Laboratorios Dermatológicos Darier S.A. de C.V., Mexico), it was necessary to establish bioequivalence to the reference product Roaccutan® (Isotretinoin; Roche, Mannheim, Germany). Three prior studies failed to establish the bioequivalence of Oratane to Mexican-sourced Roaccutan. However, 13 studies demonstrated the bioequivalence of Oratane to Roaccutane® from multiple sources. This study compared the bioavailability of Oratane with that of Mexicansourced Roaccutan and Australian-sourced Roaccutane. Methods: Study participants received each of the three agents in a randomized, open-label, 6-sequence, 3-way crossover study with a 2-week washout period between treatments. Results: Pharmacokinetic analysis revealed that peak plasma concentration (Cmax) and area under the plasma concentration-time curve from time 0 (dosing) to infinite time (AUC0–∞) were lower for Roaccutan than for Roaccutane and Oratane (Cmax: 1,023.35, 1,223.08, and 1,224.25 ng/mL, respectively; AUC0–∞: 13,653.65, 15,681.35 and 15,733.55 ng/mL×h, respectively). The 90% CIs (test/reference) for the ratios of the geometric means indicated that Oratane was bioequivalent to Roaccutane but not to Roaccutan. In addition, Roaccutane (R2) was not bioequivalent to Roaccutan (R1; R1/R2 90% CIs: Cmax, 76.12 – 91.04; AUC0–t, 82.19 – 91.13; AUC0–∞, 82.94 – 91.57). Conclusion: Oratane and Australian-sourced Roaccutane could be considered bioequivalent, but neither formulation was found to be bioequivalent to Mexican-sourced Roaccutan.Correspondence to:
Everardo Piñeyro-Garza
Francisco Fernandez Treviño 201,
Colonia Leones, Monterrey, Nuevo León, Mexico
Email: [email protected]
