Acyclovir kinetics in end-stage renal disease

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Abstract
Acyclovir (ACV) is almost entirely eliminated by the kidneys and has a terminal plasma half-life (t1/2) of 2-3 h in subjects with normal renal function. To determine the drug''s kinetics and tolerance in patients with severe renal failure, 6 anuric subjects on long-term hemodialysis were studied. Each received a 1-h infusion of 2.5 mg/kg IV ACV. The kinetics are well described by a 2-compartment open model. ACV terminal plasma t1/2 and the total body clearance were 19.5 .+-. 5.9 h (.hivin.x .+-. SD) and 28.6 .+-. 9.5 ml/min/1.73 m2. Peak (end of infusion) and 8- and 24-h plasma ACV concentrations were 37.5 .+-. 23.3, 10.3 .+-. 2.9 and 6.4 .+-. 2.4 .mu.M. Approximately 48 h after the start of the infusion the subjects were hemodialyzed for 6 h. The pre- and posthemodialysis ACV plasma levels were 2.74 .+-. 1.38 and 1.11 .+-. 0.60 .mu.M. The terminal ACV t1/2 during hemodialysis was 5.7 .+-. 0.85 h. During hemodialysis paired arterial and venous samples showed that ACV was readily dialyzed, with a mean coefficient of extraction of 0.45 .+-. 0.12. The dialysis clearance of acyclovir was 81.8 .+-. 12.6 ml/min. None of the patients had any ACV-related adverse effects. Since ACV elimination is markly reduced in end-stage renal failure and because ACV is readily hemodialyzible, dosage modifications are needed to avoid cumulation and to replace dialyzed drug.