Abstract

Acyclovir-associated renal dysfunction is difficult to study in humans because it occurs in patient populations who are generally receiving multiple medicines concurrently and dysfunctions occur infrequently. We studied the effects of two regimens of acyclovir treatment, a short-term high dose (210 mg/kg/day for 43 hr) via constant infusion and a chronic lower dose by intermittent infusion (15 mg/kg, 3 times/day for 28 days), on selected renal functions in dogs. Urine concentrating capacity as compared to base-line and controls declined during both the short-term (40% decline) and chronic treatments (36% decline). The persistence of the concentrating deficit in the presence of stimulation with vasopressin suggested that the defect resided in the renal response to vasopressin. Glomerular filtration rates significantly decreased during the acute high-dose treatment (from 104 +/- 15 to 87 +/- 11 ml/min) but not during the chronic low-dose treatment. Both acyclovir treatments were associated with a small but significant decline (approximately 10% for both studies) in the plasma potassium concentrations although an increase in urine potassium clearance could not be demonstrated. We conclude that acyclovir can cause renal dysfunction in healthy animals at plasma concentrations higher but comparable to those achieved clinically. Although both treatment regimens decreased renal function, the shorter high-dose regimen which maintained acyclovir plasma concentrations was more detrimental than the longer exposure to a lower dose of the drug given intermittently. The data suggest that renal dysfunction is not related to a rare sensitivity, as all acyclovir-treated animals showed subtle decrements in renal function.