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

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

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

Kyung Ae Chae,Hee Jung Cho,Ji Min Sung,Hee Lee,Dong Cheol Seo,Jin Suk Kim,Ho Chul Shin,Kyung Ae Chae,Hee Jung Cho,Ji Min Sung,Hee Lee,Dong Cheol Seo,Jin Suk Kim,Ho Chul Shin,

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 microg . h/ml, and C(0) of 0.2 microg/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 V(d): 4.6 l/kg; AUC: 3 microg . h/ml; t(1/2): 0.5 h; C(0): 6 microg/ml; CL(tot): 7 l/h/kg; and MRT: 0.6 h. Following oral administration of VP-0502 (100 mg/kg), it was not detectable in plasma (<50 ng/ml), while after the oral administration of VP-0502AL, VP-0502 was quantitatively detected as an active metabolite for the first 7 h, with a maximum plasma concentration (C(max)) of 0.8 microg/ml, and an area under the concentrationtime curve (AUC) of 2 microg . h/ml. The oral pharmacokinetic parameters of VP-0502AL were calculated to be: maximum concentration time (t(max)) 2.7 h; C(max) 0.2 microg/ml; elimination half-life (t(1/2)): 0.8 h; and AUC 0.5 microg . h/ml. Overall the findings indicate that VP-0502AL has a favorable pharmacokinetic profile as a prodrug with rapid transformation into the active metabolite, and that the attachment of the amino acid alanine to VP-0502 is an effective approach to improve its oral bioavailability. VP-0502AL is predicted to become a new highly bioavailable anti-AIDS drug candidate and/or lead compound.

Bioavailability of the amino acid-attached prodrug as a new anti-HIV agent in rats. Publishing Authors By Initials

KA Chae,HJ Cho,JM Sung,H Lee,DC Seo,JS Kim,HC Shin,KA Chae,HJ Cho,JM Sung,H Lee,DC Seo,JS Kim,HC Shin,

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

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of veterinary science (Suw?n-si, Korea)

VOLUME: 8

Page Numbers: 263-7

Journal Abbreviation: J. Vet. Sci.

ISSN: 1229-845X

DAY: 7

MONTH: Sep

YEAR: 2007

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

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LANGUAGE: eng

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AFFILIATION: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul, Korea.

Country: Korea (South)

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MEDLINETA: J Vet Sci

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