Disposition and metabolism of carbovir in mice dosed intravenously or orally

SM el Dareer, KF Tillery, LM Rose, RF Struck and DL Hill

Biochemistry Research Department, Southern Research Institute, Birmingham, AL 35255-5305.

To determine the disposition of carbovir and [3H]carbovir in mice, HPLC and thin-layer chromatographic assays were developed and mice were dosed iv and by gavage. Carbovir had no lethal effect at iv doses up to 500 mg/kg and was stable for 24 hr in mouse plasma at temperatures ranging from 0-37 degrees C. Binding to plasma proteins was minimal. Following an iv dose of 500 mg/kg of carbovir or [3H] carbovir, elimination phases with half-lives of 26-37 min (alpha) and 206-330 min (beta) were observed for plasma. For mice dosed with 27 mg/kg of [3H]carbovir, however, only a single phase with a half-life of 17 min was noted. Of several tissues examined, kidney contained the highest concentration of radioactivity. For the high dose, 19.0 +/- 2.6% was excreted in the urine in 24 hr as unchanged carbovir and 42.2 +/- 2.4% as metabolites; for the low dose, 54.5 +/- 6.1% was excreted as carbovir and 26.5 +/- 5.0% as metabolites. When mice were dosed orally with 500 mg/kg, plasma concentrations of carbovir were low. The initial plasma half-life for carbovir was 69 min; the terminal half-life was 822 min. Urinary excretion of unchanged carbovir was 21.3 +/- 7.1%. These results indicate that clearance of high doses of carbovir is limited and that its absorption is poor after oral dosing.

Volume 18, Issue 6, pp. 842-845, 11/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics