Disposition of intravenous radioactive acyclovir

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 <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 (<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.