The pharmacokinetics of vidarabine were studied on 22 occasions in nine infants and three older children with herpesvirus infection. The drug was administered for 10 days in doses of 15-30 mg/kg per day. Vidarabine was not detected in the serum of any patient, although small quantities were detected in the urine of two of the older children. Peak serum concentrations of arabinosyl hypoxanthine, the major metabolite of vidarabine, ranged from 2.3 to 11.4 micrograms/ml. Concentrations of this metabolite were higher in two preterm infants than in full-term infants receiving comparable doses. The mean elimination half-life estimated from cumulative urinary excretion was 2.4 hr in a preterm infant, 3.1 hr in full-term infants, and 2.8 hr in older children. Neither clearance nor half-life changed when multiple doses were administered. Vidarabine and arabinosyl hypoxanthine did not accumulate during therapy. The rates of recovery of drug from the urine and of renal clearance of arabinosyl hypoxanthine were directly related to the age and maturity of the patient. Arabinosyl hypoxanthine readily diffused into cerebrospinal fluid.

Hypoxanthine arabinoside pharmacokinetics were measured during an adenine arabinoside continuous intravenous infusion and during hemodialysis in a patient with renal failure. Therapeutic guidelines for adenine arabinoside in renal failure are provided based on an elimination half-life of 4.7 h and a plasma clearance of 87.9 ml/min for the hypoxanthine metabolite.

We studied the effect of repeated heavy physical activity on glomerular filtration rate (GFR) in healthy, uninephrectomized and experimentally uremic mice. Exercise consisted of running uphill in the inner surface of a rotating cylinder in ideal environmental temperature. In the control groups, no extra physical activity was imposed. In sham-operated and nephrectomized mice, GFR rose significantly following training. By contrast, GFR did not change significantly in the exercised mice with experimental renal failure 24 h following the last exercise session. During the same period, no significant change was observed in GFR of any of the control groups. Following training in each experimental group, mean aortic blood pressure as well as fractional kidney weight (kidney weight/body weight) were not different from the respective controls. Our results indicate that the capacity to augment GFR by physical training is dependent upon the amount of remaining functional renal tissue.

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