Bioavailability of the amino acid-attached prodrug as a new anti-HIV agent in rats

The primary objective of this study was to compare the pharmacokinetics of a new anti-human immunodeficiency virus agent 1-(2-amino-pyridin-4-ylmethyl)-6-(3,5-dimethylbenzoyl)- 5-isopropyl-1H-pyrimidine-2,4-dione (VP-0502) with its amino acid prodrug alanine amide of VP-0502 (VP-0502AL), following i...

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Published in:Journal of veterinary science (Suwŏn-si, Korea) 2007, 8(3), , pp.263-267
Main Authors: Ho-Chul Shin, Kyung-Ae Chae, Hee-Jung Cho, Ji-Min Sung, Hee Lee, Dong-Cheol Seo, Jin-Suk Kim
Format: Article
Language:Korean
Subjects:
수의학
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Summary:The primary objective of this study was to compare the pharmacokinetics of a new anti-human immunodeficiency virus agent 1-(2-amino-pyridin-4-ylmethyl)-6-(3,5-dimethylbenzoyl)- 5-isopropyl-1H-pyrimidine-2,4-dione (VP-0502) with its amino acid prodrug alanine amide of VP-0502 (VP-0502AL), following intravenous and oral administrations to rats. The plasma concentrations of both analytes were analyzed via high-performance liquid chromatography coupled with photodiode-array detection (HPLC-DAD). When VP-0502 was intravenously administered at 20 mg/ kg, the analyte appeared in low levels with an AUC of 0.3 μg · h/ml, and C0 of 0.2 μg/ml in plasma. However, both the prodrug VP-0502AL and its metabolite VP-0502 appeared at comparatively higher levels following intravenous injection of VP-0502AL at the same dose. VP-0502AL’s pharmacokinetic parameters were Vd: 4.6 l/kg; AUC: 3 μg · h/ml; t1/2: 0.5 h; C0: 6 μg/ml; CLtot: 7 l/h/kg; and MRT: 0.6 h. Following oral administration of VP-0502 (100 mg/kg), it was not detectable in plasma (
ISSN:1229-845X
1976-555X