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Pharmacokinetics and Tolerability of KM-023 in Healthy Subjects : 건강한 자원자에서 KM-023의 약동학 및 내약성에 대한 연구
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- Authors
- Advisor
- 유경상
- Major
- 의과대학 의과학과
- Issue Date
- 2014-08
- Publisher
- 서울대학교 대학원
- Keywords
- KM-023 ; pharmacokinetics ; tolerability
- Description
- 학위논문 (석사)-- 서울대학교 대학원 : 의과학과, 2014. 8. 유경상.
- Abstract
- Introduction: KM-023 is a new second-generation non-nucleoside reverse transcriptase inhibitor that is under development for the treatment of human immunodeficiency virus (HIV) type-1 infection. This study determined KM-023 pharmacokinetic characteristics and tolerability in healthy subjects.
Methods: A randomized, double-blinded, placebo-controlled, dose-escalation study was conducted in 80 healthy Korean male volunteers. The subjects were allocated to single- or multiple-dose (once daily for 7 days) study that received 75, 150, 300, or 600 mg drug or placebo in a 4:1 ratio. The plasma and urine concentrations were quantified using liquid chromatography-tandem mass spectrometry. Plasma concentration-time data of KM-023 was analyzed by using non-compartmental methods. Adverse events were reported and tolerability monitoring was conducted.
Results: The average maximum concentration (Cmax) and area under the concentration-time curve from time 0 to infinity (AUCinf) values of KM-023 for the 75-600 mg doses in the single-dose study ranged from 440.2 ng/mL to 1245.4 ng/mL and 11142.4 ng·h/mL to 33705.6 ng·h/mL, respectively. The mean Cmax at steady-state (Cmax,ss) and area under the concentration-time curve within a dosing interval (AUCτ,ss) values ranged from 385.1 ng/mL to 1096.7 ng/mL and 3698.9 ng·h/mL to 10232.6 ng·h/mL, respectively, following 75-600 mg doses in the multiple-dose study. Dose proportionality was not observed for KM-023. KM-023 showed a 0.6-fold accumulation after multiple doses in the 600-mg dose group. KM-023 was generally well tolerated.
Conclusions: KM-023 demonstrated dose- and time-dependent nonlinear pharmacokinetic characteristics after single or multiple doses over a dose range (75-600 mg) in healthy subjects. KM-023 showed favorable tolerability in this
study.
- Language
- English
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