Acyclovir kinetics in end-stage renal disease

Acyclovir (ACV) is almost entirely eliminated by the kidneys and has a terminal plasma half-life (t 1 2) of 2 to 3 hr in subjects with normal renal function. To determine the drug's kinetics and tolerance in patients with severe renal failure, six anuric subjects on long-term hemodialysis were studied. Each received a 1-hr infusion of 2.5 mg/kg IV ACV. The kinetics are well described by a two-compartment open model. ACV terminal plasma t 1 2 and the total body clearance were 19.5 ± 5.9 hr (x ± SD) and 28.6 ± 9.5 ml/min/1.73 m². Peak (end of infusion) and 8- and 24-hr plasma ACV concentrations were 37.5 ± 23.3, 10.3 ± 2.9, and 6.4 ± 2.4 μM. Approximately 48 hr after the start of the infusion the subjects were hemodialyzed for 6 hr. The pre- and posthemodialysis ACV plasma levels were 2.74 ± 1.38 and 1.11 ± 0.60 μM. The terminal ACV t 1 2 during hemodialysis was 5.7 ± 0.85 hr. 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.