Volume 54, No. 11/2016(November)
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Original Research
Persistence with antipsychotics in dementia patients in Germany
Anke Booker, Louis Jacob, Jens Bohlken, Michael Rapp, Karel Kostev
Price
42.00 $
Page No. 835
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 11/2016 (835-840)
Persistence with antipsychotics in dementia patients in Germany
Anke Booker1, Louis Jacob2, Jens Bohlken3, Michael Rapp4, Karel Kostev1
1IMS Health, Epidemiology, Frankfurt, Germany, 2Department of Biology, Ecole Normale Supérieure de Lyon, Lyon, France, 3Psychiatric Practice Bohlken, Berlin, and 4Department of Social and Preventive Medicine, University of Potsdam, Potsdam, Germany
Background/Aims: To analyze the duration of treatment with antipsychotics in German dementia patients. Methods: This study included patients aged 60 years and over with dementia who received a first-time antipsychotic prescription by psychiatrists between 2009 and 2013. The main outcome measure was the treatment rate for more than 6 months following the index date. Results: A total of 12,979 patients with dementia (mean age 82 years, 52.1% living in nursing homes) were included. After 2 years of follow-up, 54.8%, 57.2%, 61.1%, and 65.4% of patients aged 60 – 69, 70 – 79, 80 – 89, and 90 – 99 years, respectively, received antipsychotic prescriptions. 63.9% of subjects living in nursing homes and 55.0% of subjects living at home also continued their treatment (p-value < 0.001). Conclusion: The percentage of dementia patients treated with antipsychotics is very high.
Correspondence to:
Prof. Dr. rer. med. Karel Kostev
Epidemiology, Real World Evidence Solutions
IMS HEALTH GmbH & Co. OHG
Darmstädter Landstraße 108
60598 Frankfurt am Main, Germany
Email: [email protected]
Original Research
Gastrointestinal bleeding risk of non-vitamin K oral anticoagulants is similar to warfarin – a Japanese retrospective cohort study
Tsuguru Shirai, Takatsugu Yamamoto, Kazuo Kawasugi, Yasushi Kuyama, and Hiroto Kita
Price
42.00 $
Page No. 841
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 11/2016 (841-846)
Gastrointestinal bleeding risk of non-vitamin K oral anticoagulants is similar to warfarin – a Japanese retrospective cohort study
Tsuguru Shirai1#2, Takatsugu Yamamoto1, Kazuo Kawasugi1, Yasushi Kuyama1, and Hiroto Kita1
1Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, and 2Department of Gastroenterology, Ageo Chuo General Hospital, Ageo, Japan
Background and aim: Although several non-vitamin K oral anticoagulants have been developed to prevent cardiogenic thrombosis, the status of hemorrhagic complications in the clinical setting among Asian populations, including Japan, remains unclear. We conducted this retrospective cohort study to clarify the current status of hemorrhagic events during antithrombotic therapy with non-vitamin K oral anticoagulants, with particular focus on gastrointestinal bleeding. Methods: Medical charts of 475 patients prescribed dabigatran, rivaroxaban, or apixaban between April 2011 and September 2014 were reviewed to examine whether any hemorrhagic events occurred, compared with 135 patients who received warfarin between April 2009 and March 2011. Results: Incidences of total and actionable hemorrhage in patient taking non-vitamin K oral anticoagulants were 13.8% per year and 4.6% per year, respectively, showing no significant differences from those in warfarin users (9.3% per year and 5.0% per year, respectively). In addition, actionable gastrointestinal hemorrhage occurred at similar rates in non-vitamin K oral anticoagulants users (2.1% per year) and warfarin users (1.5% per year). Most hemorrhages were from the lower gastrointestinal tract, and considerable events involved perianal bleeding. Multiple regression analysis showed that age, concomitant dual antiplatelet therapy, and concomitant nonsteroidal anti-inflammatory drug therapy were significant factors related to actionable gastrointestinal bleeding. Conclusions: Risk of gastrointestinal hemorrhage in patients taking non-vitamin K oral anticoagulants was similar to that in patients taking warfarin. The dominant bleeding site was the lower gastrointestinal tract.
Correspondence to:
Takatsugu Yamamoto, MD, PhD
Department of Internal Medicine
Teikyo University School of Medicine
Kaga, Itabashi-ku, Tokyo, Japan
Email: ymmt@
med.teikyo-u.ac.jp
Original Research
Tolerability and safety of Octagam® (IVIG): a post-authorization safety analysis of four non-interventional phase IV trials
Wolfgang Frenzel, Stefan Wietek, Tor-Einar Svae, Anette Debes, Daniel Svorc
Page No. 847
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 11/2016 (847-855)
Tolerability and safety of Octagam® (IVIG): a post-authorization safety analysis of four non-interventional phase IV trials
Wolfgang Frenzel1, Stefan Wietek1, Tor-Einar Svae2, Anette Debes3, Daniel Svorc1
1Octapharma Pharmazeutika Produktionsges.m.b.H., Vienna, Austria, 2Octapharma USA Inc., Hoboken, NJ, USA, and 3Octapharma GmbH, Langenfeld, Germany*
Objective: To evaluate the tolerability and safety of Octagam® 5% and 10% across all indications, ages, and treatment regimens, using data from four non-interventional post-authorization safety studies (PASS); this analysis was performed following changes in the preparation of raw material used to manufacture Octagam. Methods: All four studies included in- and out-patients prescribed Octagam for treatment of their medical condition. Physicians used case report forms to document baseline demographics, Octagam treatment details, and data on the efficacy of Octagam, and recorded all adverse drug reactions (ADRs) and other safety data. Results: Altogether 21,780 infusions of Octagam in 2,397 patients were included in our analysis. The most frequent indication for Octagam was secondary immunodeficiencies (SID; n = 1,368, 11,348 infusions), followed by primary immunodeficiencies (PID; n = 363; 3,923 infusions). During the individual patient observation, 83% of SID and 67% of PID patients were free of any infection. In up to 85% of all investigator assessments, Octagam was rated to have a favorable effect. In autoimmune diseases, investigators assessed Octagam as being beneficial in 70% (immune thrombocytopenia) up to 100% (Guillain-Barré syndrome), depending on the indication. The majority of patients (92%) tolerated Octagam treatment without any ADR. The overall incidence of reported ADRs was 1.0% for all infusions. The majority of ADRs were considered non-serious (93%) and mild or moderate (87%) in severity. No unexpected ADR signal was detected. Conclusions: This analysis demonstrates that the changes in the preparation of raw material used to manufacture Octagam did not affect the safety profile of Octagam® 5% and 10%.
*At the time of study realization.Correspondence to:
Dr. Wolfgang Frenzel
International Medical Director
Octapharma Pharmazeutika Produktionsges.m.b.H.
Oberlaaer Str. 235, 1100 Vienna, Austria
Email: [email protected]
Original Research
Research on radiotherapy at different times of the day for inoperable cervical cancer
Li Chang, Lan Li, Wenhui Li, Meiping Jiang, Yunhe Jv, Li Wang, Yu Hou, Qing Long, and Shuhui Yu
Price
42.00 $
Page No. 856
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 11/2016 (856-863)
Research on radiotherapy at different times of the day for inoperable cervical cancer
Li Chang*, Lan Li*, Wenhui Li, Meiping Jiang, Yunhe Jv, Li Wang, Yu Hou, Qing Long, and Shuhui Yu
Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Cancer Hospital of Yunnan Province, Kunming, China
Purpose: To investigate the radiation effects and acute damage in inoperable cervical cancer patients irradiated at different times as well as the underlying mechanisms. Methods: 67 patients were randomized to a morning group (MG, 9:00 – 11:00 AM) and an evening group (EG, 9:00 – 11:00 PM) and both received external beam radiotherapy (RT) (50 Gy in 25 fractions) at different times. Brachytherapy (36 – 42 Gy in 6 – 7 fractions) was also performed to enhance the radiation response twice every week in all patients at the same time. Clinical therapeutic effects and acute toxicities were evaluated after RT. Flow cytometry was analyzed before and after RT. Results: Patients’ response to radiation was similar in the two groups. Incidences of overall and high-grade (III – IV) diarrhea in the MG vs. the EG were 75.0% vs. 57.6% and 12.5% vs. 6.1%, respectively. The incidence of severe hematological toxicity in the EG was significantly increased compared to the MG group. Cell apoptosis in the EG was significantly higher at 9:00 – 11:00 PM than that at 9:00 – 11:00 AM after RT. No significant differences were found in Gap Phase 0/Gap Phase 1 (G0/G1), Gap Phase 2/Metaphase Phase (G2/M), and Synthesis Phase (S) phase between different times and groups, nor were expressions of Per1, Per2, and Clock. But expressions of Per1, Per2, and Clock were significantly negative with G2/M phase and positively correlated with cell apoptosis. Conclusion: RT at different time intervals results in similar efficacy. However, RT in the morning reduces severe hematological toxicity. Radiation responses may be associated with circadian genes by influence of cell cycles and apoptosis.
*These authors contributed equally to this work.Correspondence to:
Wenhui Li, MD, PhD
Department of Radiation Oncology
The Third Affiliated Hospital of Kunming Medical
University
Cancer Hospital of Yunnan Province
No.519 Kunzhou Road, Kunming 650118, China
Email: liwenhui64_25@
126.com.
Original Research
Comparative analysis of the efficacy of low- and moderate-intensity statins in Korea
Hun-Sung Kim, Hyeseon Lee, Bumjoon Park, Seungho Park, Hyunah Kim, Seung-Hwan Lee, Jae Hyoung Cho, Kun-Ho Yoon, Bong-Yun Cha, Ju Han Kim, and In Young Choi
Price
42.00 $
Page No. 864
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 11/2016 (864-871)
Comparative analysis of the efficacy of low- and moderate-intensity statins in Korea
Hun-Sung Kim1#2, Hyeseon Lee3, Bumjoon Park1#4, Seungho Park1#4, Hyunah Kim5, Seung-Hwan Lee6, Jae Hyoung Cho6, Kun-Ho Yoon6, Bong-Yun Cha6, Ju Han Kim2, and In Young Choi1
1Department of Medical Informatics, College of Medicine, The Catholic University of Korea, 2Division of Biomedical Informatics, Systems Biomedical Informatics Research Center, Seoul National University College of Medicine, 3Department of Industrial and Management Engineering, Pohang University of Science and Technology, 4Department of Information System, Hanyang University, 5College of Pharmacy, Sookmyung Women’s University, and 6Department of Endocrinology and Metabolism, College of Medicine, The Catholic University of Korea, Seoul, Korea
Purpose: The American College of Cardiology/American Heart Association (ACC/AHA) guidelines are based on studies with a limited number of Asian subjects; therefore, they are difficult to apply to Asian patients, including Korean patients. Materials and methods: Data were extracted from the clinical data warehouse system of Seoul St. Mary’s hospital (January 2010 – December 2012) to determine the percent change in low-density lipoprotein cholesterol (LDL-C) levels at an average 3 and 6 months from baseline. Statins with statistically similar lowering effects were placed in one group (group A, B, or C). The proportions of patients who achieved LDL-C < 100 mg/dL were compared between baseline LDL-C levels: low (< 130 mg/dL), medium (130 – 160 mg/dL), and high (> 160 mg/dL). Results: The majority of the 9 statins of various doses (2,349 patients) were effective at 3 months, with additional, smaller decreases at 6 months. The LDL-C lowering effect of group A (atorvastatin (20 mg), rosuvastatin (10 mg)) was ~ 45%; that of group B (atorvastatin (10 mg), pitavastatin (2 mg), pravastatin (40 mg), simvastatin (20 mg)) was 35 – 37%. groups A and B contained only moderate-intensity statins (ACC/AHA guidelines). With baseline LDL-C ≥ 130 mg/dL, greater proportions of patients achieved LDL-C < 100 mg with atorvastatin (20 mg) and rosuvastatin (10 mg). Conclusion: Because of the demonstrated LDL-C lowering effects and target achievement rates, the ACC/AHA guidelines might not apply to Korean patients. Korean treatment guidelines should consider statins with relatively low potency. Additional studies regarding appropriate statin doses should be conducted with Asian populations.Correspondence to:
In Young Choi, PhD
Department of Medical Informatics
The Catholic University of Korea
505 Banpo-Dong, Seocho-Ku, Seoul 137-701, Korea
Email: [email protected]
Original Research
Sedation and use of analgesics in endoscopic retrograde cholangiopancreatography: a double-blind comparison study of meperidine/midazolam, remifentanil/ midazolam, and remifentanil alone
Jinhua Zhang, Yong Huang, Zhao Li, Jian Li, Kunpeng Liu, and Chenghui Li
Price
42.00 $
Page No. 872
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 11/2016 (872-879)
Sedation and use of analgesics in endoscopic retrograde cholangiopancreatography: a double-blind comparison study of meperidine/midazolam, remifentanil/ midazolam, and remifentanil alone
Jinhua Zhang1, Yong Huang2, Zhao Li2, Jian Li2, Kunpeng Liu2, and Chenghui Li2
1Department of Anesthesiology, Dongfang Hospital, Beijing University of Chinese Medicine, District Fengtai, and 2Department of Anesthesiology, China-Japan Friendship Hospital, District Chaoyang, Beijing, China
Purpose: To compare the efficacy and remifentanil with midazolam for conscious sedation during endoscopic retrograde cholangiopancreatography (ERCP). Methods: 99 patients scheduled for ERCP were randomly allocated to be treated with either meperidine/midazolam (group C, n = 33), remifentanil (group R, n = 33), or the remifentanil plus midazolam (group RM, n = 33). In group C, intermittent intravenous meperidine and midazolam were administrated during the procedure; in group R, remifentanil was infused continuously at a rate of 0.2 μg/kg/min for 5 minutes preoperatively, and decreased to 0.15 μg/kg/min when the procedure began; in group RM, midazolam 0.02 mg/kg was administered preoperatively, and remifentanil was administered in the same manner as in group R. Blood pressure, heart rate, respiratory rate, O2-saturation, and bispectral index (BIS) of the patients were recorded. The modified Aldrete scores, operator satisfaction scores, and side effects of the patients were noted as were the operative duration and anesthesia duration. Results: The blood pressure of the patients were significantly increased in group R and group C compared to baseline, and no significant changes were noted in group RM. Group RM experienced the least variability in heart rate. BIS was decreased the most in groups C and RM. Hypoxemia was observed most frequently in group RM. Nausea and pain was highest in group C. Amnesia was most often reported in groups C and RM. Operator satisfaction and modified Aldrete of the patients was increased in group R. Conclusion: Both continuous remifentanil infusion alone and remifentanil plus midazolam provided satisfactory analgesia when used for sedation for ERCP, however, continuous remifentanil infusion alone resulted in increased operator satisfaction scores and expedited recoveryroom discharge.Correspondence to:
Kunpeng Liu, MD
Department of Anesthesiology
China-Japan Friendship Hospital
2# Yinghuadong Street, District Chaoyang, Beijing, 100029, China
Email: [email protected]
Original Research
Expert consensus on the use of liraglutide in the treatment of diabetes in internal medicine
Carlos Calvo Gómez, Ricardo Gómez-Huelgas, Joan Lima Ruiz, Lluis Masmiquel Comas, Alfredo Michán Doña, and Antonio Zapatero Gaviria
Price
42.00 $
Page No. 880
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 11/2016 (880-889)
Expert consensus on the use of liraglutide in the treatment of diabetes in internal medicine
Carlos Calvo Gómez1, Ricardo Gómez-Huelgas2, Joan Lima Ruiz3, Lluis Masmiquel Comas4, Alfredo Michán Doña5, and Antonio Zapatero Gaviria6
1Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, 2Hospital Regional Universitario, Málaga, 3Hospital Vall d´Hebrón, Barcelona, 4Hospital Son Llàtzer, Palma de Mallorca, 5Hospital de Jérez, and 6Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain*
Background: Type 2 diabetes mellitus (DM2) is a disease of epidemic proportions. In the adult Spanish population, prevalence of DM2 is nearly 14%, which makes its monitoring and treatment imperative. Liraglutide has achieved relevance due to its efficacy and safety in DM treatment. The aim of this study is to gather expert opinion on diabetes to assess the current role of liraglutide in DM2. Materials/methods: The survey was performed by 57 internal medicine specialists using the Delphi method. The questionnaire had 56 items regarding liraglutide in DM treatment. Results: Consensus was reached in 71.4% of items. Panelists stated agreement regarding liraglutide suitability in the treatment of patients with DM2, high cardiovascular risk, and with pathologies related to obesity, highlighting its role in weight loss, low risk of hypoglycemia, and improvement of vascular risks. Moreover, consensus was not reached regarding the suitability of liraglutide in patients with special situations, mainly due to minimal experience caused by the small number of patients. Conclusions: Due to its safety and hypoglycemic efficacy, liraglutide is an excellent choice for DM treatment in combination with other drugs. Its effects on the reduction of weight and other cardiovascular risk factors, make it an optimal treatment, especially in overweight or obese patients.
*All authors (listed alphabetically) have contributed equally to this work.Correspondence to:
Dr. Ricardo Gómez Huelgas
Servicio de Medicina Interna
Hospital Regional de Málaga
Av. Carlos Haya, s/n, 29010 Málaga, Spain
Email: [email protected]
Original Research
Effect of ulinastatin on serum inflammatory factors in Asian patients with acute pancreatitis before and after treatment: a meta-analysis
Ling-Zhang Wang, Ming-Yu Luo, Jin-Shan Zhang, Fu-Gui Ge, Jian-ling Chen, Chang-Qing Zheng
Price
42.00 $
Page No. 890
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 11/2016 (890-898)
Effect of ulinastatin on serum inflammatory factors in Asian patients with acute pancreatitis before and after treatment: a meta-analysis
Ling-Zhang Wang1, Ming-Yu Luo1, Jin-Shan Zhang2, Fu-Gui Ge3, Jian-ling Chen1, Chang-Qing Zheng4
1Department of Emergency, 2Department of Radiology, LinYi People’s Hospital, 3Department of Surgery, Linyi Women’s and Children’s Hospital, LinYi, and 4Department of Gastroenterology, Shengjing Hospital, China Medical University, Shenyang, China
Objective: We applied a meta-analysis to explore the effect of ulinastatin (UTI) on the serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) in Asian patients with acute pancreatitis (AP). Methods: Various databases were searched based on stringent inclusion and exclusion criteria to extract relevant cohort studies. Comprehensive Meta-analysis 2.0 (Biostat Inc., Englewood, NJ, USA) was applied for statistical analyses. Results: A total of 113 relevant studies (67 in Chinese, 46 in English) were initially retrieved. Finally, 11 eligible studies were enrolled in our meta-analysis with 399 pancreatitis patients. Meta-analysis results showed that after being treated with UTI, the serum levels of CRP, IL-6, and TNF-α were evidently decreased (CRP: SMD = –2.697, 95% CI = –4.399 ~ –0.994, p = 0.002; IL-6: SMD = –5.268, 95% CI = –9.850 ~ –0.687, p = 0.024; TNF-α: SMD = –5.666, 95% CI = –11.083 ~ –0.249, p = 0.040). Conclusion: UTI can effectively reduce the serum levels of CRP, IL-6, and TNF-α in Asian patients with AP, suggesting that UTI has anti-inflammatory effect on Asian patients with AP.
Correspondence to:
Dr. Jian-ling Chen
Department of Emergency, LinYi People’s Hospital
NO.27 Jiefang Road, Lanshan District, LinYi 276000, P.R.China
Email: chenjianling1008@
163.com
Original Research
Relationship of microRNA 616 gene polymorphism with prognosis of patients with premature coronary artery disease
Yan Zhang, Shijie Wang, Yongqin Li, Chunyan Zhang, Jiahong Xue, Xiaosan Wu, and Congxia Wang
Price
42.00 $
Page No. 899
Abstract
arterioInternational Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 11/2016 (899-903)
Relationship of microRNA 616 gene polymorphism with prognosis of patients with premature coronary artery disease
Yan Zhang1, Shijie Wang2, Yongqin Li1, Chunyan Zhang1, Jiahong Xue1, Xiaosan Wu1, and Congxia Wang1
1Department of Cardiology, the Second Hospital of Xi’an Jiaotong University, and 2Department of Physiology and Pathophysiology, Medical School of Xi’an Jiaotong University, Xi’an, Shaanxi, China
Objective: To investigate the relationship of microRNA 616 (has-miR-616) single nucleotide polymorphisms (SNPs) and its target gene paraoxonase 1 (PON 1) with the prognosis of patients with premature coronary artery disease (pCAD). Methods: 266 pCAD cases in the case group and 300 cases in the control group were collected. Using the polymorphism method of polymerase chain reaction and restriction fragment length, the has-miR-616 rs3735590 genotypes of target gene PON 1 were detected. Results: In the changes of rs3735590 C/T SNPs, compared with CC genotypes, the risk of coronary heart disease of the individuals carrying CT and TT genotypes were reduced by 42% and 31%, respectively (p < 0.05). The risk of developing coronary heart disease in individuals carrying CT and TT genotypes were reduced significantly in the population with levels of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. Conclusion: Target gene PON 1 of hsa-miRNA-616 rs3735590C-T SNPs is associated with the reduced incidence risk of pCAD, and carrying C alleles is an independent risk factor for pCAD.Correspondence to:
Dr. Yongqin Li
Department of Cardiology
The Second Hospital of Xi’an Jiaotong University
No. 157 Xuwu Road, Xi’an, Shaanxi 710004, China
Email: [email protected]
Original Research
Pharmacokinetics and tolerability of intravenous ibuprofen injection in healthy Chinese volunteers: a randomized, open-label, single- and multiple-dose study
Huili Zhou, Wei Xu, Guolan Wu, Lihua Wu, Jianzhong Shentu, Zhengfei Pan, Shuai Hu, Yang Liu
Price
42.00 $
Page No. 904
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 11/2016 (904-913)
Pharmacokinetics and tolerability of intravenous ibuprofen injection in healthy Chinese volunteers: a randomized, open-label, single- and multiple-dose study
Huili Zhou1, Wei Xu1, Guolan Wu1, Lihua Wu1, Jianzhong Shentu1, Zhengfei Pan2, Shuai Hu2, Yang Liu3
1Research Center of Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 2Hainan Herui Pharmaceutical Co., Ltd., Haikou, and 3Eliving-pharm technology Co., Ltd., Shenyang, China
Objective: Recently a formulation of intravenous (IV) ibuprofen was developed in China for management of mild to moderate pain in patients who could not take oral medications or where intravenous administration was preferable. The aim of this study was to evaluate the pharmacokinetic properties and tolerability of single and multiple doses of ibuprofen injection in healthy Chinese volunteers. Methods: This open-label, single- and multiple-dose study was conducted in healthy Chinese volunteers. In the single-dose phase, subjects were randomized to receive a single dose of ibuprofen injection 0.2, 0.4, or 0.8 g administered as a 30-minute IV infusion with a 1-week washout between periods. Blood samples were collected at regular intervals from 0 to 12.5 hours after drug administration and were analyzed using a validated LC-MS/MS method. In the multiple-dose phase, subjects received 0.4 g ibuprofen every 6 hours for 9 doses. Blood samples were obtained before the 7th, 8th, and 9th administration to determine the Cmin at steady state; on the 9th intravenous administration, blood samples were also collected for 12.5 hours after drug administration. Pharmacokinetic parameters were estimated using a noncompartmental model. Tolerability was determined using clinical evaluation and monitoring of adverse events (AEs). Results: A total of 12 healthy male (n = 6) and female (n = 6) Chinese volunteers were enrolled and completed the trial. After IV administration of single dose, the mean (SD) Cmax value increased from 35.77 (6.98) to 117.12 (19.78) µg/mL, and the mean (SD) AUC0–t value increased from 67.63 (10.30) to 230.50 (33.55) µg×h/mL in the range of 0.2-g to 0.8-g dose. The terminal half-life in plasma was ~ 2.0 hours. After IV administration of 9 doses of ibuprofen 400 mg every 6 hours, the mean (SD) Cmax was 66.49 (8.49) µg/mL, the AUC0–t was 135.65 (26.91) µg×h/mL, the t1/2 was 2.14 (0.34) hours, the Cl/F was 3.34 (0.68) L/h, and the Vz/F was 10.32 (2.69) L, which were comparable with those after single dosing. The accumulation index was 1.17 (0.06), and the fluctuation was 304.0 (57.7) %. Results of the t-tests of Cmax and AUC found no significant differences between the male and female groups. No serious AEs were reported, and there were no discontinuations due to AEs. Conclusion: The pharmacokinetics of ibuprofen exhibited dose-related kinetics from the 0.2- to the 0.8-g dose. After multiple doses, the pharmacokinetic parameters of ibuprofen were consistent with those after single doses. There was no accumulation in ibuprofen exposure in healthy Chinese between multiple doses and single dose. At the doses studied, ibuprofen appeared to be well tolerated in these healthy volunteers.
Correspondence to:
Jianzhong Shentu, MR
Research Center of Clinical Pharmacy
State Key Laboratory for Diagnosis and
Treatment of Infectious Diseases
First Affiliated Hospital, College of Medicine
Zhejiang University
No. 79 Qingchun Road, Hangzhou 31003, China
Email: [email protected]
Original Research
Evaluation of a novel autoinjector for subcutaneous self-administration of belimumab in systemic lupus erythematosus
Saira Z. Sheikh, Anne E. Hammer, Norma Lynn Fox, James Groark, Herbert Struemper, David Roth, and David Gordon
Page No. 914
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 11/2016 (914-922)
Evaluation of a novel autoinjector for subcutaneous self-administration of belimumab in systemic lupus erythematosus
Saira Z. Sheikh1, Anne E. Hammer2, Norma Lynn Fox3, James Groark4, Herbert Struemper5, David Roth4, and David Gordon4
1University of North Carolina, Chapel Hill, 2GSK, Research Triangle Park, NC, 3GSK, Potomak, MD, 4GSK, Philadelphia, PA, and 5PAREXEL International, Research Triangle Park, NC, USA
Objective: To study self-administration and pharmacokinetics (PK) of subcutaneous (SC) belimumab in patients with systemic lupus erythematosus (SLE). Methods: Patients previously treated with belimumab self-administered belimumab 200 mg SC weekly for 8 weeks using an autoinjector. The primary endpoint was the proportion of patients able to self-administer their first and second dose (weeks 1 and 2) in the clinic. The proportion able to self-administer at weeks 4 and 8 (clinic) and weeks 3, 5, 6, and 7 (home) were secondary endpoints. Belimumab PK, safety, and injection-site pain were assessed. Results: 91/95 patients completed the study (withdrawals: adverse events (AEs): 3; lost to follow-up: 1). 93% were female, and mean (SD) age was 44.8 (12.50) years. The majority (99%, 89/90; no attempt, n = 5) successfully self-administered belimumab SC at weeks 1 and 2 (5 had clinic staff assistance), and 98% (85/87) successfully self-administered at weeks 4 and 8. Home-administration success rates were high (93%, (81/87) at weeks 3, 5, 6, and 7). Week 8 median trough concentration was 113 µg/mL. For patients with a ≤ 1.5-week interval between IV SC administration, week-1 concentrations were higher vs. week 8 (+ 51% median) but within a range observed with IV dosing; those with a ≥ 2.5-week interval had median differences close to 0. AEs and serious AEs were low, with no deaths; pain levels were low and decreased with subsequent injections. Conclusion: Patients with SLE successfully self-administered belimumab SC using a novel autoinjector; the PK profile was stable following a switch from IV with acceptable AE and pain levels. The recommended dosing interval between IV to SC dosing is 1 – 4 weeks.
Correspondence to:
Saira Z. Sheikh, MD
Assistant Professor of Medicine
Rheumatology, Allergy & Immunology
University of North Carolina at Chapel Hill
Thurston Arthritis Research Center
3300 Thurston Building, CB 7280, Chapel Hill, NC 27599-7280, USA
Email: [email protected]
Case
Report
Staphylococcus aureus osteo-articular infection: usefulness of the determination of daptomycin serum concentration to explain a treatment failure
Sylvain Barreau, Sihem Benaboud, Solen Kernéis, Laurence Moachon, Philippe Blanche, Matthieu Groh, Laurent Massias, Jean-Marc Treluyer, Claire Poyart, and Josette Raymond
Price
42.00 $
Page No. 923
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 11/2016 (923-927)
Staphylococcus aureus osteo-articular infection: usefulness of the determination of daptomycin serum concentration to explain a treatment failure
Sylvain Barreau1, Sihem Benaboud2, Solen Kernéis3, Laurence Moachon4, Philippe Blanche5, Matthieu Groh5, Laurent Massias6, Jean-Marc Treluyer2, Claire Poyart1, and Josette Raymond1
1Université Paris Descartes, Service de Bactériologie, Hôpitaux Universitaires Paris Centre Cochin–Broca-Hôtel Dieu, Paris, 2EA7323, Université Paris Descartes, Sorbonne Paris Cité, Paris, France, Service de Pharmacologie Clinique, Hôpitaux Universitaires Paris Centre Cochin–Broca-Hôtel Dieu, Paris, France, Université Paris Descartes, 3Université Paris Descartes, Equipe mobile d’infectiologie, Hôpitaux Universitaires Paris Centre Cochin–Broca-Hôtel Dieu, Paris, 4Service de Pharmacovigilance, Hôpitaux Universitaires Paris Centre Cochin–Broca-Hôtel Dieu, Paris, 5Service de Médecine Interne, Hôpital Cochin, Université Paris V- René Descartes, Paris, and 6Laboratoire de Pharmacologie et Toxicologie, Hôpital Bichat Claude Bernard, Hôpitaux Universitaires Paris Nord Val-de-Seine, Paris, France
We report two cases of treatment failure in patients with osteoarticular infection associated with Staphylococcus aureus bacteremia and receiving daptomycin. Using a published population-pharmacokinetic model and daptomycin blood level in these patients, area under the curve (AUC) was calculated and compared to the pharmacological target. For the first patient, treated with 6 mg/kg every 48 hours due to acute renal failure and then every 24 hours, the AUC was 820 mg×h×L–1, with a minimal concentration of 23.5 mg/L confirming the right dose adjustment and the absence of underdosing. The methicillin-resistant Staphylococcus aureus (MRSA) strain was still susceptible to daptomycin, but it was not sufficient to observe a favorable outcome. For the second patient, treated with 10 mg/kg/d, the steady state residual concentration was 10.4 mg/L, and the calculated AUC value was 550 mg×h×L–1. AUC/MIC values evolved during treatment to be under the cut-off for bactericidal effects (> 800 hours), and the Staphylococcus aureus (SA) strain became daptomycin resistant. This study highlights the inter-individual pharmacokinetic variation leading sometimes to drug underdosing. Drug monitoring should be encouraged in order to avoid treatment failure.Correspondence to:
Dr. Josette Raymond
Laboratoire de Bactériologie, Hôpitaux Universitaires
Paris Centre Cochin-Broca-Hôtel Dieu
27 rue du Faubourg-Saint-Jacques
75679 Paris Cedex 14, France
Email: [email protected]
Bioavailability Section
A bioequivalence study of two omeprazole formulations in healthy male volunteers
Yu Kyong Kim, Seonghae Yoon, Kyung-Sang Yu, Bo-Hyung Kim, and Sung-Vin Yim
Price
42.00 $
Page No. 928
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 11/2016 (928-934)
A bioequivalence study of two omeprazole formulations in healthy male volunteers
Yu Kyong Kim1, Seonghae Yoon1, Kyung-Sang Yu1, Bo-Hyung Kim2, and Sung-Vin Yim2
1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, and 2Department of Clinical Pharmacology and Therapeutics, Kyung Hee University College of Medicine and Hospital, Seoul, Korea
Objective: This study had a single-dose, randomized, open-label, 2-period, and 2-sequence crossover design to evaluate pharmacokinetic (PK) bioequivalence between the test and reference formulations. Methods and materials: Of the 34 healthy male volunteers enrolled, 4 were excluded owing to consent withdrawal before drug administration and the remaining 30 subjects were administered 20 mg each of the test and reference formulations of omeprazole. The blood samples for PK analysis were collected at the scheduled time-points, prior to dosing to 10 hours after dosing. Plasma concentrations of omeprazole were quantified by a liquid chromatography-tandem mass spectrometry method. Bioequivalence was assessed according to current guidelines issued by regulatory authorities. Results: The plasma concentration-time profiles of omeprazole were similar between the reference and test drugs. The geometric mean ratios (90% confidence interval: CI) of test to reference were 0.9104 (0.8538 – 0.9708) for peak plasma concentration (Cmax) and 0.9304 (0.8836 – 0.9796) for area under the plasma concentration-time curve from time zero to time of last measureable concentration (AUC0–t). Conclusion: The results from the PK analysis suggested that the reference and test formulations of 20 mg omeprazole capsules were bioequivalent in healthy male subjects.Correspondence to:
Sung-Vin Yim, MD, PhD
Department of Clinical Pharmacology and Therapeutics
Kyung Hee University College of Medicine and Hospital
23 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea
Email: [email protected]
