Plasma levels and urinary excretion of vidarabine after repeated dosing

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Abstract
Vidarabine (Vira‐A) was given intravenously for 5 days to 5 immunosuppressed patients with herpes zoster. The daily dose, 10 mg/kg, was given by slow infusion over 12 hr. Blood samples were taken at 0, 1, 2, 4, 8, and 12 hr on days 1, 3, and 5. Twenty‐four‐hour urine specimens were collected before treatment and on days 1,3, and 5. Blood and urine specimens were assayed for vidarabine and its principal metabolite, hypoxanthine arabinoside (ara‐Hx), by high‐pressure liquid chromatography. The results showed that vidarabine is quickly deaminated; virtually all of the drug present in the plasma and urine was in the form of ara‐Hx. The highest plasma level, approximately 3 µg/ml, was at the end of the infusion period. The urinary‐excretion of ara‐Hx accounted for between 40% and 50% of the dose. The renal clearance values varied, but were close to the expected glomerular filtration rate of 125 ml/min. The plasma levels and the excretion levels were much the same on days 1, 3, and 5, indicating that drug did not cumulate. The results of the study were consistent with those observed in single‐dose studies. The results indicated that the infusion of vidarabine is clinically appropriate, since therapeutic plasma levels are reached promptly, drug is rapidly excreted, and there is no cumulation. Clinical Pharmacology and Therapeutics (1980) 27, 690–696; doi:10.1038/clpt.1980.98