Disposition of intravenous radioactive acyclovir

Journal Article · Sun Nov 01 04:00:00 EST 1981 · Clin. Pharmacol. Ther.; (United States)

DOI:https://doi.org/10.1038/clpt.1981.218· OSTI ID:5511035

de Miranda, P; Good, S S; Laskin, O L; Krasny, H C; Connor, J D; Lietman, P S

The kinetic and metabolic disposition of (8-14C)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 m2. 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 less than 2% excretion in the feces and only trace amounts in the expired Co2. 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 (less than 0.2% of dose) had the retention time of 8-hydroxy-9-((2-hydroxyethoxy)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.

• Research Organization: Wellcome Research Laboratories, Research Triangle Park, NC
• OSTI ID: 5511035
• Journal Information: Clin. Pharmacol. Ther.; (United States), Journal Name: Clin. Pharmacol. Ther.; (United States) Vol. 30:5; ISSN CLPTA
• Country of Publication: United States
• Language: English

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