Dustri Online Services

Search Results

Books: 0	Journals: 1	Articles: 4

Original Research

Evaluation of the pharmacokinetic interaction between the dipeptidyl peptidase IV inhibitor LC15-0444 and pioglitazone in healthy volunteers

Sung Eun Kim, SoJeong Yi, Kwang-Hee Shin, Tae-Eun Kim, Min-Jeong Kim, Youn Hoa Kim, Seo Hyun Yoon, 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. 17 - 23

Abstract

Evaluation of the pharmacokinetic interaction between the dipeptidyl peptidase IV inhibitor LC15-0444 and pioglitazone in healthy volunteers

Sung Eun Kim¹, SoJeong Yi¹, Kwang-Hee Shin¹, Tae-Eun Kim¹, Min-Jeong Kim², Youn Hoa Kim³, Seo Hyun Yoon¹, Joo-Youn Cho¹, Sang-Goo Shin¹, In-Jin Jang¹ and Kyung-Sang Yu¹

¹Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, ²Department of Clinical Development and ³Department of DMPK, LG Life Sciences, Ltd, Seoul, Republic of Korea
Objective: LC15-0444, a newly developed selective dipeptidyl peptidase IV inhibitor, has the potential to be administered with other antihyperglycemic agents. The aim of this study was to investigate the interaction between LC15-0444 and pioglitazone by comparing the pharmacokinetics of both compounds and their metabolites. Methods: A randomized, open-label, multiple dosing, three-sequence, three-period, three-treatment crossover study was performed in healthy volunteers. The three treatment groups were comprised of LC15-0444 200 mg, pioglitazone 30 mg, or coadministration of both drugs once daily for 12 days. Blood samples were collected up to 48 hours after the last dosing. Safety and tolerability were assessed throughout the study. Results: The geometric mean ratios (GMRs; (LC15-0444+Pioglitazone coadministered)/(LC15-0444 or Pioglitazone alone)) (90% confidence intervals (CIs)) for C_max,ss and AUC_t,ss of LC15-0444 were 1.06 (0.96 – 1.16) and 0.98 (0.93 – 1.03), respectively. In the case of pioglitazone, the GMRs (90% CIs) for C_max,ss and AUC_t,ss were 0.84 (0.73 – 0.96) and 0.85 (0.76 – 0.96), respectively. All reported adverse events were mild in intensity. Conclusions: The pharmacokinetics of LC15-0444 and its metabolites were not altered by pioglitazone. The systemic exposure of pioglitazone was decreased by 15% after coadministration of LC15-0444 with pioglitazone, but this was not judged to be clinically relevant, considering the total active moiety of pioglitazone.Correspondence to:
K.-S. Yu, MD, PhD
Department of Pharmacology and Clinical Pharmacology
Seoul National University
College of Medicine and Hospital
101 Daehak-ro, 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]

Original

Primary and secondary prevention of stroke and cardiovascular events using evolocumab and alirocumab: Meta-analysis of randomized controlled trials 

Kwang-Hee Shin and Hye Duck Choi

Price
42.00 $

Add to Cart

Price

42.00 $

Volume 62 (2024) p. 250 - 258

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 62 – No. 6/2024 (250-258)

Primary and secondary prevention of stroke and cardiovascular events using evolocumab and alirocumab: Meta-analysis of randomized controlled trials 

Kwang-Hee Shin¹ and Hye Duck Choi²

¹College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, and ²College of Pharmacy, Yeungnam University, Gyeongbuk, Republic of Korea
Objectives: Although the clinical role of protein convertase subtilisin kexin type 9 (PCSK9) inhibitors for cholesterol management is increasing, the post-marketing period of use is short compared to other lipid-lowering drugs, so there is still insufficient evidence for their efficacy and safety. In this meta-analysis, we evaluated preventive effects of stroke and cardiovascular (CV) events using evolocumab and alirocumab.
Materials and methods: We assessed the relative risk of stroke and CV events after alirocumab or evolocumab treatment in individuals with or without clinical CV diseases compared with that in controls. In addition, we evaluated the relative risk of hemorrhagic stroke.
Results: A total of 25 articles were included (median of study duration = 52 weeks). The risk of stroke was significantly decreased after treatment with alirocumab or evolocumab (primary prevention in patients without CV diseases: RR = 0.733; 95% CI, 0.618 – 0.870; secondary prevention in patients with CV diseases: RR = 0.703; 95% CI, 0.562 – 0.880). The risk of CV events also significantly decreased in patients treated with alirocumab or evolocumab (primary prevention: RR = 0.818; 95% CI, 0.777 – 0.861; secondary prevention: RR = 0.725; 95% CI, 0.578 – 0.910). The relative risk of hemorrhagic stroke was not significantly different between PCSK9 inhibitor-treated patients and controls (RR = 1.041; 95% CI, 0.690 – 1.573).
Conclusion: Our findings indicate that evolocumab and alirocumab are significantly effective without increasing the risk of hemorrhagic stroke. Based on this, the PCSK9 inhibitors can be highly recommended for cholesterol management.Correspondence to:
Hye Duck Choi, PhD
College of Pharmacy, Yeungnam University
280 Daehak-Ro, Gyeongsan
Gyeongbuk 38541, Republic of 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