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The disposition of acyclovir in different species

P de Miranda, HC Krasny, DA Page and GB Elion

The absorption, distribution and biotransformation of the antiviral drug acyclovir were investigated in several species. Its oral administration resulted in better absorption and higher plasma levels in the dog and mouse than in the rat and rhesus monkey. Although more total drug was absorbed, the fraction of the oral dose of acyclovir absorbed declined with increasing doses of drug. When 14C-labeled acyclovir was given s.c. to mice and rats it was distributed into all the tissues examined, including the brain. In the dog, the drug was present in the cerebrospinal fluid, the aqueous humor and saliva after an oral dose. Binding of acyclovir to plasma proteins was less than 35%. In metabolism studies with radioactive acyclovir, high-performance liquid chromatography showed that 94 and 95% of the urinary radioactivity in mice and rats was unchanged acyclovir. Minor urinary metabolites were identified as 9-carboxymethoxymethylguanine and 8- hydroxy-9-(2-hydroxy-ethoxymethyl)guanine. There was no enhanced metabolism of the drug after its repeated daily administration to mice or dogs.

Volume 219, Issue 2, pp. 309-315, 11/01/1981
Copyright © 1981 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics.