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Disposition of intravenous radioactive acyclovir
Author(s) -
Miranda Paulo,
Good Steven S,
Laskin Oscar L,
Krasny Harvey C,
Connor James D,
Lietman Paul S
Publication year - 1981
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1981.218
Subject(s) - chemistry , metabolite , pharmacokinetics , urine , half life , pharmacology , excretion , blood plasma , urinary system , high performance liquid chromatography , free fraction , volume of distribution , chromatography , endocrinology , medicine , biochemistry
The kinetic and metabolic disposition of (8‐ 14 C)acyclovir (ACV) was investigated in five subjects with advanced malignancy. The drug was administered by 1‐hr intravenous infusion at doses of 0.5 and 2.5 mg/kg. Plasma and blood radioactivity‐time, and plasma concentration‐time data were defined by a two‐compartment open kinetic model. There was nearly equivalent distribution of radioactivity in blood and plasma. The overall mean plasma half‐life and total body clearance ± SD of ACV were 2.1 ± 0.5 hr and 297 ± 53 ml/min/1.73 m 2 . Binding of ACV to plasma proteins was 15.4 ± 4.4%. Most of the radioactive dose excreted was recovered in the urine (71% to 99%) with <2% excretion in the feces and only trace amounts in the expired CO 2 . Analyses by reverse‐phase high‐performance liquid chromatography indicated that 9‐(carboxymethoxymethyl)guanine was the only significant urinary metabolite of ACV, accounting for 8.5% to 14.1% of the dose. A minor metabolite (<0.2% of dose) had the retention time of 8‐hydroxy‐9‐[(2‐hxdroxyethoxy)methyl]guanine. Unchanged urinary ACV ranged from 62% to 91% of the dose. There was no indication of ACV cleavage to guanine. Renal clearance of ACV was approximately three times the corresponding creatinine clearances. Clinical Pharmacology and Therapeutics (1981) 30, 662–672; doi: 10.1038/clpt.1981.218