| Pharmacokinetic analysis for the development of new potent anti-HIV-1 agents, the KR-V series |
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Young-mi Lee1, Jin-suk Kim2, Sang-seop Han1, Ho-chul Shin1 |
1Department of Pharmacokinetics & Toxicokinetics, Korea Research Institute of Chemical Technology
2College of Veterinary Medicine, Konkuk University |
| 새로운 항HIV-1제, KR-V series의 개발을 위한 약물동태연구 |
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이영미1, 김진석2, 한상섭1, 신호철1 |
1한국화학연구소 약물독성동태연구실
2건국대학교 수의과대학 |
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| Abstract |
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The pharmacokinetic properties of KR-V compounds, recently developed as new anti-HIV agents, were studied after i.v. and p.o. administration in rats. The concentrations of the KR-V series were determined in rat plasma using an high-performance liquid chromatography (HPLC)-UV detection system. Of the 19 KR-V compounds investigated in the present study, only KR-V 3, 10, 14, 16 and 18-1 showed oral bioavailability. The plasma concentration-time data could be adequately described by an one-compartment open model. In the i.v. kinetic study (10mg/kg), the CLt of KR-V 3, 10, 14 and 16 (>4L/hr/kg) were significantly higher than that of KR-V 18-1 (1.1 L/hr/kg). The AUC of KR-V 18-1 was greater ($8.97{mu}g{cdot}hr/ml$) than that of the other compounds, but the Vd (0.58 L/kg) was lower. In the p.o. kinetic study (50mg/kg), although the t-1/2 of KR-V 18-1 was shorter than that of the other compounds, the AUC ($3.659{mu}g{cdot}hr/ml)$ and $C_{max}(1.891{mu}g/ml$) were markedly higher. In a seperated in vitro experiment, only KR-V 18-1, of the 5 compounds with bioavailibility, exhibits potent activity against HIV-1 mutant strains. Therefore, KR-V 18-1 is expected to become a new potent anti-AIDS drug candidate/lead compound. |
| Key Words:
anti-HIV agent, pharmacokinetics, KR-V, rat, mutant strain |
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