Volume 53, No. 11/2015(November)
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Original Research
VKORC1 gene polymorphisms and adverse events in Croatian patients on warfarin therapy
Dario Mandic, Nada Bozina, Sanja Mandic, Marina Samardzija, Andrea Milostic-Srb, and Lada Rumora
Price
42.00 $
Page No. 905
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 11/2015 (905-913)
VKORC1 gene polymorphisms and adverse events in Croatian patients on warfarin therapy
Dario Mandic1, Nada Bozina2, Sanja Mandic3,4, Marina Samardzija3,5, Andrea Milostic- Srb3,6, and Lada Rumora7
1Institute of Public Health for Osijek-Baranya County, Osijek, 2Clinical Institute of Laboratory Diagnosis, University of Zagreb, School of Medicine, Zagreb University Hospital Center, Department of Pharmacology, Zagreb, 3Faculty of Medicine, University of Osijek, 4Department of Clinical Laboratory Diagnostics, 5Department of Transfusion Medicine, 6Department of Gynecology and Obstetrics, Osijek, University Hospital, Osijek, and 7Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia
Objective: The objective was to determine the impact of VKORC1 polymorphisms on warfarin anticoagulant therapy (stable warfarin maintenance dose, time required to reach therapeutic dose and time spent in therapeutic range) and its adverse events (overanticoagulation and bleeding events, time to first overanticoagulation or bleeding event, and therapy for bleeding events) in Croatian patients. Materials: Blood samples were collected from 186 patients on stable warfarin therapy. Methods: VKORC1 1173C>T and VKORC1 –1639G>A gene polymorphisms were analyzed using real-time PCR. Prothrombin time international normalized ratio (INR) values were determined and overanticoagulation as well as bleeding events were recorded. Results: Both tested VKORC1 gene polymorphisms (VKORC1 1173C>T and VKORC1 –1639G>A) were in perfect linkage disequilibrium. Genotype analysis showed that 33.9% of patients were homozygous for wild-type, 46.8% were heterozygous and 19.4% were homozygous for the variant allele. We have found a statistically significant difference between variantallele carriers and wild-type patients in stable warfarin maintenance dose (p < 0.001) and incidence of bleeding events (p = 0.040). Patients homozygous for variant-allele were more likely to experience an overanticoagulation event in the first 30 days of therapy (p = 0.040). Conclusions: Our study showed that VKORC1 1173C>T and VKORC1 –1639G>A gene polymorphisms are associated with stable warfarin maintenance dose and adverse events of warfarin therapy.Correspondence to:
Dario Mandic
Institute of Public Health for Osijek-Baranya County
F. Krezme 1, Osijek, Croatia
Email: [email protected]
Original Research
Transformation of alkylating regimen of thiotepa into tepa determines the disease progression through GSTP1 gene polymorphism for metastatic breast cancer patients receiving thiotepa containing salvage chemotherapy
Xinna Zhou, Xiaoli Wang, Qingkun Song, Huabing Yang, Xishan Zhu, Jing Yu, Guohong Song, Lijun Di, Jun Ren,Hong Shao, and Herbert Kim Lyerly
Price
42.00 $
Page No. 914
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 11/2015 (914-922)
Transformation of alkylating regimen of thiotepa into tepa determines the disease progression through GSTP1 gene polymorphism for metastatic breast cancer patients receiving thiotepa containing salvage chemotherapy
Xinna Zhou1, Xiaoli Wang1, Qingkun Song1, Huabing Yang1, Xishan Zhu1, Jing Yu2, Guohong Song2, Lijun Di2, Jun Ren1,Hong Shao3, and Herbert Kim Lyerly4
1Beijing Key Lab for Therapeutic Cancer Vaccines, Department of Medical Oncology, Capital Medical University Cancer Center, Beijing Shijitan Hospital, 2Department of Medical Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital and Institute, Peking University School of Oncology, 3Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China, and 4Department of Surgery, Duke University Medical Center, Durham, NC, USA
Background: The shifts to second-line chemotherapy for metastatic breast cancer (MBC) were widely required based on pharmaceutical molecular profiles to reach out precision medicine. The emerging precise treatment of cancer requires the implementation of clarified pharmacogenetic profiles which are capable of elucidating the predictive responses to cancer chemotherapy. Therefore we were interested in the analysis of the roles of single nucleotide polymorphism (SNP) of GSTP1 (glutathione S-transferase pi 1 gene) alleles to identify pharmacological links with predictors of clinical responses and toxicities. Methods: 93 MBC patients receiving thiotepa plus docetaxel chemotherapy were enrolled in this study. Optimized CYP3A5, CYP2B6, and GSTP1 were predominantly selected as candidate genes and their three SNPs (CYP2B6 G516T, CYP3A5 A6986G, and GSTP1 A313G) were genotyped by matrix-assisted laser desorption ionization/time of flight (MALDI-TOF) mass spectrometry. Progression-free survival (PFS), disease control rate, and chemo-related toxicities were recorded. Results: GSTP1 A313G (rs1695) was identified to be related with disease progression. In particular, patients harboring AG/GG genotype demonstrated a statistically longer PFS than those with AA. Multivariate analysis confirmed that AG/GG genotype was associated with both clinical responses and liver-localized metastatic lesions. No correlation was found between these three SNPs and chemotherapy-induced toxicity. Conclusions: These results suggest that the GSTP1 polymorphism is a novel prognostic marker for clinical response to thiotepa-containing chemotherapy regimens. Such evidence could provide insight into the role of pharmacogenetics to deprive of biases in shifting regimens solely by empirical choices.Correspondence to:
Jun Ren, MD, PhD
Beijing Key Lab for Therapeutic Cancer Vaccines
Department of Medical Oncology
Capital Medical University Cancer Center
Beijing Shijitan Hospital
10 Tieyi Road, Haidian District
Beijing, 100038 China
or
Hong Shao, PhD
Department of Pharmacy Administration and Clinical Pharmacy
School of Pharmaceutical Sciences, Peking University
38 Xueyuan Road, Haidian District, Beijing, 100191 China
Email: [email protected] or [email protected]
Appendix
Effects of statins on the mortality and mechanical ventilation duration of acute lung injury patients: a meta-analysis of five randomized controlled trials
Ping Yang, Dong-Sheng Hong, Jian Chen, Xia Zheng, Xiao-Yang Lu, Yong-Zhong Du, Xing-Guo Zhang, and Sai-Ping Jiang
Price
42.00 $
Page No. 923
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 11/2015 (923-932)
Effects of statins on the mortality and mechanical ventilation duration of acute lung injury patients: a meta-analysis of five randomized controlled trials
Ping Yang1#, Dong-Sheng Hong#, Jian Chen, Xia Zheng2, Xiao-Yang Lu1, Yong-Zhong Du3, Xing-Guo Zhang1, and Sai-Ping Jiang1
1Department of Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 2Intensive Care Unit, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, and 3College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
AppendixCorrespondence to:
Sai-Ping Jiang, Pharm D
Department of Pharmacy
The First Affiliated Hospital, College of Medicine, Zhejiang University
79 Qingchun Road, Hangzhou, 310003, PR China
Email: [email protected]
Original Research
Effect of liraglutide vs. NPH in combination with metformin on blood glucose fluctuations assessed using continuous glucose monitoring in patients with newly diagnosed type 2 diabetes
Zejun Ma, Rui Chen, Yan Liu, Pei Yu, and Liming Chen
Price
42.00 $
Page No. 933
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 11/2015 (933-939)
Effect of liraglutide vs. NPH in combination with metformin on blood glucose fluctuations assessed using continuous glucose monitoring in patients with newly diagnosed type 2 diabetes
Zejun Ma, Rui Chen, Yan Liu, Pei Yu, and Liming Chen
2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
Background: To evaluate the effect of liraglutide and NPH on blood glucose fluctuations in patients with newly diagnosed type 2 diabetes mellitus (T2DM). Methods: A total of 63 newly diagnosed T2DM patients were randomized into a liraglutide group and an NPH group. They were treated for 12 weeks. The values of CGM, HbA1C, and BMI were measured and compared before and after treatment. Results: FPG, HbAlc, and MBG were decreased in both groups after 12 weeks of treatment. In the liraglutide group, the MAGE, SDBG, LAGE, BMI, and waist circumference were significantly 1ower than in the NPH group (p < 0.05). Patients in the liraglutide group had a greater incidence of gastrointestinal adverse effects than in the NPH group (p < 0.05). The incidence of hypoglycemia episode in the liraglutide group was significantly lower than in the NPH group (p < 0.05). Conclusions: Liraglutide achieved improvements in overall glycemic control similar to NPH in patients with newly diagnosed T2DM. Liraglutide was associated with less glucose fluctuation than NPH treatment as assessed by CGM. In addition, patients in the liraglutide group had a greater incidence of gastrointestinal adverse effects, a lower incidence of hypoglycemia, and some weight reduction.Correspondence to:
Liming Chen, MD, PhD
2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics
Key Laboratory of Hormone and Development (Ministry of Health)
Metabolic Disease Hospital & Tianjin Institute of Endocrinology
Tianjin Medical University
Tianjin 300070, China
Email: [email protected]
Original Research
Pharmacotherapeutic aspect of antibiotic therapy during acute community-acquired pneumonia in adults at the University Hospital of Cocody (Abidjan)
Gisèle Kouakou-Siransy, Kigninlman Horo, Etienne Effo, Alexis Kamenan, Geneviève N’guessan-Irié, Alexandre Boko-Kouassi, Elisabeth Aka-Anguy, and Henri Die Kakou
Price
42.00 $
Page No. 940
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 11/2015 (940-946)
Pharmacotherapeutic aspect of antibiotic therapy during acute community-acquired pneumonia in adults at the University Hospital of Cocody (Abidjan)
Gisèle Kouakou-Siransy1,3, Kigninlman Horo2, Etienne Effo3, Alexis Kamenan3, Geneviève N’guessan-Irié3, Alexandre Boko-Kouassi2, Elisabeth Aka-Anguy, and Henri Die Kakou1
1Service of Clinical Pharmacology, 2Service of Pneumophtisiology, University Hospital of Cocody, and 3Service of Pharmacology, Formation and Research Unit of Pharmaceutical and Biological Sciences, University Félix Houphouët Boigny, Abidjan, Ivory Coast
Objective: Acute community-acquired pneumonia in Côte d’Ivoire, mainly in the pneumology units, is the second most common cause of hospitalization after tuberculosis. This study aimed to evaluate the compliance of antibiotic therapy during bacterial acute community-acquired pneumonia with international guidelines serving as frame of reference at the University Hospital of Cocody. Materials and methods: We carried out a descriptive retrospective and analytic study on 62 hospitalized patients from December 1, 2008 to November 30, 2010 in the Pneumophtisiology department at the University Hospital of Cocody (Abidjan). The prescription of antibiotics was compared with the recommendations of the 15th consensus conference on anti-infectious therapy by the Société de Pathologie Infectieuse de Langue Française (SPILF) (French Speaking Society of Infectious Pathology) held in 2006. Results: The main antibiotics prescribed were amoxicillin-clavulanic acid (42.27%), netilmicin (34.5%) and ciprofloxacin (6%). The antibiotic therapy diagrams were dominated by an antibiotic bitherapy; the association of amoxicillin-clavulanic acid + netilmicin was observed in 80.64% of the prescriptions. An antibiotic monotherapy was reported in 14.52% of the prescriptions. Apyrexia at 72 hours was obtained with 64% of the patients with nonstop antibiotic treatment, 24% of them presented a lack of apyrexia, and 12% of them died. The lack of apyrexia at 72 hours treatment correlated with concomitant administration of cotrimoxazole with prophylactic doses among HIV positive patients. The level of the compliance with the SPILF recommendations is low (3.6%). Conclusion: Thus, our results convey the necessity to draw up national recommendations because of the specific realities of countries with limited incomes.Correspondence to:
Gisèle Kouakou-Siransy, PharmD
Service of Clinical Pharmacology
University Hospital of Cocody, BP 405, Abidjan 08, Ivory Coast
Email: [email protected]
Original Research
Population pharmacokinetics of tenofovir in HIV/HBV co-infected patients
Baralee Punyawudho, Narukjaporn Thammajaruk, Parawee Thongpeang, Gail Matthews, Sharon R. Lewin, David Burger, Kiat Ruxrungtham, and Anchalee Avihingsanon
Price
42.00 $
Page No. 947
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 11/2015 (947-954)
Population pharmacokinetics of tenofovir in HIV/HBV co-infected patients
Baralee Punyawudho1*, Narukjaporn Thammajaruk2, Parawee Thongpeang2, Gail Matthews3, Sharon R. Lewin4,5, David Burger6, Kiat Ruxrungtham2,7, and Anchalee Avihingsanon2,7
1Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 2HIV-NAT, Thai Red Cross AIDS Research Center, Bangkok, Thailand, 3Kirby Institute, University of New South Wales, Sydney, 4Department of Infectious Diseases, Alfred Hospital and Monash University, 5Center for Biomedicine, Burnet Institute, Melbourne, Australia, 6Radboud University Nijmegen Medical Center & Nijmegen Institute for Infection, Inflammation and Immunology (N4i), Nijmegen, The Netherlands, and 7Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Objective: Tenofovir is an efficacious drug with a long half-life and high activity against both HIV and HBV. However, the pharmacokinetics of tenofovir have not been studied in HIV/HBV co-infected patients. Data from HIV mono-infected patients may not be transferable to HIV/HBV co-infected population because the nature and consequences of the co-infection are different. This study developed a population pharmacokinetic model of tenofovir in patients with HIV/HBV co-infection and identified pathophysiologic factors that affect the pharmacokinetics of the drug. Methods: Sparse and intensive blood samples were collected from patients with HIV/HVB coinfection. The population pharmacokinetic model of tenofovir was developed by a nonlinear mixed-effects modeling approach (NONMEM®). Results: A total of 332 tenofovir plasma concentrations from 146 patients were obtained. A two-compartment model best described the pharmacokinetics of tenofovir. Creatinine clearance (estimated by Cockcroft and Gault equation) affected the tenofovir apparent clearance (CL/F). Tenofovir CL/F decreased by 23.5% when concomitantly used with atazanavir/ritonavir. Conclusions: Based on the results from our study, it was shown that the pharmacokinetics of tenofovir in HIV/HBV co-infected patients are comparable to those with HIVmonoinfection. This study confirmed that patients with kidney impairment and the concurrent use of atazanavir/ritonavir will require the dosage of tenofovir to be adjusted to ensure efficacy and prevent unwanted toxicities. The developed model can reliably be used to adjust for the dosage of tenofovir in this population, especially when therapeutic drug monitoring services are unavailable.Correspondence to:
Baralee Punyawudho, PhD
Department of Pharmacy Practice
Faculty of Pharmaceutical Sciences
Chulalongkorn University, Bangkok, Thailand 10330
Email: [email protected]
Original Research
Factors affecting intrasubject variability of PK exposure: absolute oral bioavailability and acidic nature of drugs
Masahiko Sato and Mamoru Narukawa
Price
42.00 $
Page No. 955
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 11/2015 (955-962)
Factors affecting intrasubject variability of PK exposure: absolute oral bioavailability and acidic nature of drugs
Masahiko Sato and Mamoru Narukawa
Department of Clinical Medicine (Pharmaceutical Medicine), Kitasato University Graduate School of Pharmaceutical Sciences, Tokyo, Japan
Objectives: The aim of the present study is to investigate factors affecting intrasubject variability of pharmacokinetic (PK) exposure, which affect the results of bioequivalence (BE) studies. We focused on two factors: absolute oral bioavailability (BA) and acidic nature of drugs. Methods: Intrasubject coefficient of variation (CV) for Cmax and AUC was estimated based on the 90% confidence intervals (CIs) and the number of subjects from fasting BE study results for our investigation. Relationships between the intrasubject CV and the absolute oral BA as well as the acidic nature of the drugs were investigated. Results: First, the relationship between absolute oral BA and intrasubject variability of PK exposure (Cmax and AUC) showed negative log-linear relationship in the BE studies following oral administration of 65 immediate-release drugs under fasted condition. Drugs with poor absolute oral BA of less than 5% showed high intrasubject CV in the range of 30 – 65%. In contrast, drugs with high absolute oral BA of more than 80% showed low intrasubject CV of less than 20%. Second, acidic drugs with pKa < 6 had higher intrasubject CV of Cmax than AUC compared to other types of drugs. The intrasubject CV ratios of Cmax to AUC for acidic drugs with pKa < 6 were significantly higher than those for other types of drugs. Conclusion: Results show that absolute oral BA is one of the major factors that predict the extent of intrasubject variability of PK exposure. Acidic nature of drugs is thought to be an additional factor increasing intrasubject variability of Cmax as compared to AUC.Correspondence to:
Masahiko Sato, Master of Pharmacy
Department of Clinical Medicine (Pharmaceutical Medicine)
Kitasato University Graduate School of Pharmaceutical Sciences
Shirokane 5-9-1, Minato-ku, Tokyo 108-8641, Japan
Email: [email protected]
Original Research
A randomized, placebo-controlled repeat-dose thorough QT study of inhaled loxapine in healthy volunteers
James V. Cassella, Daniel A. Spyker, and Paul P. Yeung
Page No. 963
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 11/2015 (963-971)
A randomized, placebo-controlled repeat-dose thorough QT study of inhaled loxapine in healthy volunteers
James V. Cassella, Daniel A. Spyker, and Paul P. Yeung
Alexza Pharmaceuticals, Inc., Mountain View, CA and Teva Pharmaceuticals, Frazer, PA, USA
Objective: This randomized, double-blind, active- and placebo-controlled, crossover, thorough QT study assessed the effect of two inhaled loxapine doses on cardiac repolarization as measured by corrected QT (QTc) interval in healthy subjects (ClinicalTrials.gov NCT01854710). Methods: Subjects received two doses of inhaled loxapine (10 mg) 2 hours apart + oral placebo, two doses of inhaled placebo + oral placebo, or two doses of inhaled placebo + oral moxifloxacin (400 mg; positive control), with ≥ 3 days washout between treatments. Two-sided 90% confidence intervals (CIs) were calculated around least-squares mean predose placebo-subtracted individually corrected QT durations (ΔΔTcIs) at 12 time points throughout 24 hours after dosing. A ΔΔTcI 95% upper CI exceeding 10 msec was the threshold indicating QTc prolongation (primary endpoint). Secondary endpoints included Fridericia- and Bazettcorrected QT duration and QTcI outliers. Pharmacokinetics and adverse events (AEs) were also assessed. Results: Of 60 subjects enrolled (mean age, 33.8 years; 52% male), 44 completed the study. Post loxapine dosing, no ΔΔTcI 95% upper CI exceeded 10 msec; the largest was 6.31 msec 5 minutes post dose 2. Methodology was validated by ΔΔTcI 95% lower CIs exceeding 5 msec at 9 of 12 time points after moxifloxacin dosing. Loxapine plasma concentrations increased rapidly (mean Cmax, 177 ng/mL; median tmax 2 minutes after dose 2, 2.03 hours after dose 1). There were no deaths, serious AEs, or AEs leading to discontinuation, and one severe AE. Conclusions: Primary and secondary endpoints indicated two therapeutic doses of inhaled loxapine did not cause threshold QTc prolongation in this study.Correspondence to:
Paul P. Yeung, MD, MPH
Teva Pharmaceuticals
41 Moores Road, Frazer, PA 19355, USA
Email: [email protected]
Bioavailability Section
Ibuprofen lysinate, quicker and less variable: relative bioavailability compared to ibuprofen base in a pediatric suspension dosage form
Juan Manuel Ferrero-Cafiero, Ignasi Gich, Montse Puntes, Joan Martínez, Maria R. Ballester, Jimena Coimbra, Yaira Mathison, Maite Tarré, Xavier Font, and Rosa M. Antonijoan
Price
42.00 $
Page No. 972
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 11/2015 (972-979)
Ibuprofen lysinate, quicker and less variable: relative bioavailability compared to ibuprofen base in a pediatric suspension dosage form
Juan Manuel Ferrero-Cafiero1,2, Ignasi Gich1,2, Montse Puntes1,2, Joan Martínez1,2, Maria R. Ballester1,2, Jimena Coimbra1,2, Yaira Mathison1, Maite Tarré3, Xavier Font3, and Rosa M. Antonijoan1,2
1Centre d’Investigació de Medicaments, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, (CIM-Sant Pau), 2Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, and 3Laboratorio de Aplicaciones Farmacodinámicas, S.A. (FARDI), Barcelona, Spain
Objectives: To assess and compare the bioavailability of ibuprofen enantiomers (R and S) of two different pediatric suspensions: the first one with ibuprofen lysinate (Algidrin® Pediátrico, FARDI S.A., Barcelona, Spain) and the second one with ibuprofen base (Dalsy®, Abbott Laboratories S.A., Madrid, Spain). Methods: A randomized, open-label, single-dose, balanced, crossover study under fasting conditions was performed at the CIM-Sant Pau. 24 healthy volunteers received a single dose of ibuprofen lysinate (Algidrin® Pediátrico, FARDI S.A.) and ibuprofen base (Dalsy®, Abbott Laboratories S.A.) equivalent to 400 mg of ibuprofen. 18 blood samples were drawn and ibuprofen enantiomer plasma concentrations were determined using an enantioselective analytical method. An analysis of variance (ANOVA) model was used, and the 90% confidence intervals (CI) were calculated; further analyses were made regarding rate of absorption and variability. Results: The pharmacokinetic parameters (Algidrin® Pediátrico vs. Dalsy® (Mean ± SD)) were: S-enantiomer: Cmax = 22.39 ± 5.33 vs. 19.97 ± 3.19 μg/mL; AUC0t = 74.83 ± 16.69 vs. 74.64 ± 14.80 μg×h/mL, and AUC0∞ = 77.46 ± 19.33 vs. 76.98 ± 17.13 μg×h/mL; and for R-enantiomer: Cmax = 21.74 ± 3.76 vs. 15.20 ± 2.03 μg/mL; AUC0t = 57.55 ± 10.17 vs. 46.13 ± 9.61 μg×h/mL, and AUC0∞ value was 58.49 ± 10.57 vs. 47.03 ± 10.02 μg×h/mL. The tmax (Median) for S-enantiomer (active) were: 0.5 vs. 1.33 hours (p = 0.001) and for R-enantiomer: 0.5 vs. 1.0 hours (p = 0.004). Ibuprofen pharmacokinetic values may vary under fed state and in pediatric population. Conclusions: While S-ibuprofen shows a similar bioavailability for AUC0t, AUC0∞, and Cmax, R-ibuprofen shows suprabioavailability for the lysinate formulation. The rate of absorption of the ibuprofen lysinate suspension is quicker and less variable than that of the ibuprofen base reference suspension and it exhibits a shorter tmax, which is of particular interest for achieving a rapid and homogeneous analgesic and antipyretic effect.Correspondence to:
Juan Manuel Ferrero-Cafiero, PharmD
Centre d’Investigació de Medicaments
Institut de Recerca de l’Hospital de
la Santa Creu i Sant Pau (CIM-Sant Pau)
Sant Antoni Ma Claret 167, 08025 Barcelona, Spain
Email: [email protected]
Bioavailability Section
Pharmacokinetic comparisons of two acetyl-L-carnitine formulations in healthy Korean volunteers
Sang-Min Baek, Renhua Zheng, Eun-Jung Seo, Dae-Yeon Hwang, and Bo-Hyung Kim
Price
42.00 $
Page No. 980
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 11/2015 (980-986)
Pharmacokinetic comparisons of two acetyl-L-carnitine formulations in healthy Korean volunteers
Sang-Min Baek1, Renhua Zheng1, Eun-Jung Seo1, Dae-Yeon Hwang1, and Bo-Hyung Kim1,2
1Department of Clinical Pharmacology and Therapeutics, and 2East-West Medical Research Institute, Kyung Hee University College of Medicine and Hospital, Seoul, Republic of Korea
Background: Acetyl-L-carnitine (ALC) has demonstrated neuroprotective effects in several experiments and is widely prescribed to reduce cognitive impairment in Alzheimer’s disease patients or manage neuropathic symptoms in diabetic patients. Objectives: This study was designed to assess the pharmacokinetic (PK) bioequivalence between a new generic (test) formulation of ALC hydrochloride 590 mg and a branded (reference) formulation of ALC hydrochloride 590 mg in healthy Korean male volunteers. Methods: This was a randomizedsequence, single-dose, two-way crossover study. All subjects randomly received one formulation of the test or reference tablet and the other formulation with a 7-day washout period. Blood samples (7 mL) were collected immediately before dosing, and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, and 12 hours postdose. The plasma concentrations of ALC were analyzed using liquid chromatography tandem mass spectrometry. Tolerability was assessed throughout the study. Results: The PK profiles of both formulations showed similar rends. The mean (± SD) baseline (predose) concentration of ALC was 1.23 ± 0.31 μg/mL and 1.09 ± 0.30 μg/mL for the test and the reference formulations, respectively. The mean Cmax for the test and reference formulations were 1.74 ± 0.43 μg/mL and 1.68 ± 0.48 μg/mL, respectively. The mean AUClast of ALC was 12.96 ± 1.89 μg×h/mL and 12.49 ± 2.44 μg×h/mL for the test and reference formulations, respectively. The geometric mean ratios of test/reference (90% CI) were 1.050 (0.960 – 1.149) for Cmax and 1.048 (1.000 – 1.099) for AUClast. Both formulations were well tolerated in all treatment groups. Conclusion: The test and the reference formulations of ALC were bioequivalent with regard to the PK parameters.Correspondence to:
Bo-Hyung Kim, MD, PhD
Department of Clinical Pharmacology and Therapeutics
East-West Medical Research Institute
Kyung Hee University College of Medicine and Hospital
Seoul, Republic of Korea, 23 Kyungheedae-ro,
Dongdaemun-gu, Seoul 130-872, Korea
Email: [email protected]
