Dustri Online Services

Search Results

Books: 0	Journals: 1	Articles: 3

Original Research

Pharmacokinetics of a fixed-dose glimepiride/sustained-release metformin combination

Kyu-pyo Kim, Kyoung Soo Lim, Bo-Hyung Kim, Hyun-Suk Shin, Joo-Youn Cho, Sang-Goo Shin, In-Jin Jang and Kyung-Sang Yu

Price
42.00 $

Add to Cart

Price

42.00 $

Volume 50 p. 142 - 149

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 50 – No. 2/2012 (142-149)

Pharmacokinetics of a fixed-dose glimepiride/sustained-release metformin combination

Kyu-pyo Kim¹*, Kyoung Soo Lim*, Bo-Hyung Kim, Hyun-Suk Shin, Joo-Youn Cho, Sang-Goo Shin, In-Jin Jang and Kyung-Sang Yu

Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, Seoul, Korea

*Both authors contributed equally to this work.
¹Current affiliation: Department of Internal Medicine, Ulsan University College of Medicine and Asan Medical Center, Seoul, Korea
Objective: Pharmacokinetic (PK) profiles of glimepiride and metformin have been established for the combination drug as well as each agent individually. However, the PK profiles of a combination drug containing glimepiride and sustainedrelease (SR) metformin have not been reported. To compare the pharmacokinetic profiles of glimepiride/SR metformin (2 mg/500 mg) with the PK of immediate-release (IR) formulations, an open-label, randomized, 3-period, 3-sequence, 3-treatment, crossover study was conducted in 12 healthy subjects. Methods: After a single administration of glimepiride/SR metformin 2 mg/500 mg (Treatment) or glimepiride/metformin IR 2 mg/500 mg (Reference 1), or administration of 2 doses of glimepiride/metformin IR 1 mg/250 mg 12 h apart (Reference 2), serial blood samples were collected and drug concentrations determined by liquid chromatography/ tandem mass spectrometry. PK parameters (C_max and AUC₂₄) for glimepiride and metformin were log-transformed and compared using a mixed-effects model analysis of variance (ANOVA). The mean differences and 95% confidence intervals (CIs) were back-transformed to obtain geometric mean ratios along with the CIs for the ratios. Results: Treatment demonstrated similar systemic exposures for glimepiride; the geometric mean ratio (95% CIs) for glimepiride AUC₂₄ was 1.05 (0.97 – 1.13) for Treatment relative to Reference 1 and 1.08 (1.00 – 1.17) for Treatment relative to Reference 2. The SR formulation showed a delay in the time to reach maximum concentration for metformin from 1.0 – 4.0 h to 4.0 – 8.0 h and a decreased AUC₂₄ value; the geometric mean ratio for metformin AUC₂₄ was 0.87 (0.74 – 1.03) for Treatment relative to Reference 1 and 0.75 (0.63 – 0.88) for Treatment relative to Reference 2. Conclusions: This study demonstrates for the first time that fixed-dose glimepiride and SR metformin 2 mg/500 mg shows a PK profile similar to that of glimepiride, but with a delayed time to maximum concentration and slightly decreased bioavailability for metformin compared with the IR fixed-dose combination, in healthy volunteers. PK profiles from this exploratory study will be helpful in designing and conducting further studies in diabetic patients.Correspondence to:
Kyung-Sang Yu, MD, PhD
Department of Pharmacology and Clinical Pharmacology
National University College of Medicine and Hospital
101 Daehangno, Jongno-gu, Seoul 110-744, Korea
Email: [email protected]

Original Research

A positron emission tomography microdosing study with sertraline in healthy volunteers

Kwang-Hee Shin, Kyu-pyo Kim, Kyoung Soo Lim, Ji Who Kim, Yun-Sang Lee, Bo Yeun Yang, Jae Sung Lee, Jae-Min Jung, Seo-Hyun Yoon, In-Jin Jang and Kyung-Sang Yu

Price
42.00 $

Add to Cart

Price

42.00 $

Volume 50 p. 224 - 232

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 50 – No. 3/2012 (224-232)

A positron emission tomography microdosing study with sertraline in healthy volunteers

Kwang-Hee Shin¹, Kyu-pyo Kim¹, Kyoung Soo Lim¹, Ji Who Kim², Yun-Sang Lee², Bo Yeun Yang², Jae Sung Lee², Jae-Min Jung², Seo-Hyun Yoon¹, In-Jin Jang¹ and Kyung-Sang Yu¹

¹Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, and ²Department of Nuclear Medicine, Seoul National University College of Medicine and Hospital, Seoul, Korea
Objective: This study explored microdosing methods for evaluating the distribution and pharmacokinetics (PK) of a central nervous system (CNS) drug candidate. Methods: We used sertraline as a model drug. In this open-label, one-arm, three-period, multiple-dosing study, 10 healthy male volunteers received 6-day administrations of sertraline at doses of 5, 25 or 50 mg/d in three different periods. Before the first dose of Period 1, and 24 h after the last dose of each period, an intravenous bolus of [¹¹C]sertraline was injected for positron emission tomography (PET) scanning. After the sixth dose in each period, serial blood samples were collected at scheduled intervals over 48 h; then serum sertraline concentrations were determined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Sertraline was distributed in the brain within 20 min, and it was highly distributed in the putamen, cingulate, and thalamus. Linearity in steady-state C_max and AUC_last were observed in the 5 – 50 mg dose range. The results suggested that microdosing with PET was a useful method for exploring the bloodbrain- barrier penetration and distribution of a candidate CNS drug. Conclusions: This study described a microdosing method that combined PET with LC-MS/MS for determining the brain distribution and PK characteristics of a CNS drug candidate.Correspondence to:
Kyung-Sang Yu, MD, PhD
Assistant Professor of Clinical Pharmacology
College of Medicine
Seoul National University Clinical Trials
Center Seoul National University Hospital
101 Daehangno, Jongno-gu,
Seoul, 110-744 Korea
Email: [email protected]

Original Research

Multiple-dose pharmacokinetics of fesoterodine sustained-release in healthy Korean volunteers

Dongseong Shin, Kwang-Hee Shin, SeungHwan Lee, Kyoung Soo Lim, Joo-Youn Cho, In-Jin Jang, Sang-Goo Shin and Kyung-Sang Yu

Price
42.00 $

Add to Cart

Price

42.00 $

Volume 50 p. 722 - 728

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 50 – No. 10/2012 (722-728)

Multiple-dose pharmacokinetics of fesoterodine sustained-release in healthy Korean volunteers

Dongseong Shin, Kwang-Hee Shin, SeungHwan Lee, Kyoung Soo Lim, Joo-Youn Cho, In-Jin Jang, Sang-Goo Shin and Kyung-Sang Yu

Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea
Objective: Fesoterodine is a pro-drug of the active metabolite 5-hydroxymethyl tolterodine (5-HMT), a muscarinic receptor antagonist. This study aimed to evaluate the safety profile and pharmacokinetic characteristics of multiple oral doses of sustained-release fesoterodine (fesoterodine SR) in healthy Korean males. Methods: A randomized, double-blind, placebo-controlled, multiple-dose study with two oral doses (4 mg and 8 mg) was conducted in healthy Korean male participants. The study drug was administered once daily for 5 days. The plasma concentration of 5-HMT was measured up to 72 hours after the last drug administration. The CYP2D6 genotype was analyzed using polymerase chain reaction (PCR) methods to assess the effect of genetic polymorphisms on the pharmacokinetic parameters. Results: 20 participants completed the study. The mean (SD) areas under the plasma concentration-time curves during the dosing interval (AUC_τ) of the 4 mg and 8 mg dose groups were 26.1 (8.0) and 64.2 (30.5) μg∙h/ml and the mean peak concentrations (C_max) were 2.6 (0.7) and 6.0 (2.0) μg/ml, respectively, at steady-state. The mean AUC_τ and C_max of 5-HMT increased in approximately the same proportion as the dose increased. Fesoterodine SR was well tolerated without any serious adverse events or abnormal clinical laboratory findings. Conclusion: Systemic 5-HMT exposure showed dose-proportional characteristics in the 4 mg to 8 mg dose range in healthy Korean males. Thus, 4 mg or 8 mg doses of fesoterodine SR taken once-daily were tolerable in healthy Korean males.Correspondence to:
Kyung-Sang Yu, MD, PhD
Department of Clinical Pharmacology and Therapeutics Seoul
National University College of Medicine and Hospital Seoul
101 Daehangno, Jongno-gu
Seoul 110-744, Korea
Email: [email protected]

Shopping Overview

Shopping Overview
Type	Qtty	Discount	VAT	Price
Your basket is empty

View Cart

Search Results

Shopping Overview

Send us an E-Mail