Pharmacokinetic profile of acyclovir in a child receiving continuous kidney replacement therapy for acute liver failure.

Abstract

Continuous venovenous hemodiafiltration (CVVHDF) is one of the treatments of critically ill children presenting severe acute liver failure. This affliction might be induced by HSV infection requiring a treatment by acyclovir. Continuous kidney replacement therapy (CKRT) can alter its pharmacokinetics, according to its physicochemical properties and CVVHDF settings. The patient was a 21-month-old female presenting liver failure with hyperammonemia treated by acyclovir with presumed HSV infection. CKRT was initiated on day 1 with substantial replacement and dialysate flow rates (respectively 75 and 220mL/kg/h). Acyclovir was intravenously administered every 8h with a 1-h infusion of 500mg/m2. Plasma and effluent concentrations were measured by liquid chromatography-tandem mass spectrometry assay to estimate the area under a curve (AUC) and CKRT clearance by 2 methods (one based on pre- and post-filter concentrations and the other one on dialysate flow rates). Clearance was estimated between 19.2 and 26.3mL/min with the first method and between 27.6 and 44.3mL/min with the second one. Concentrations were highly above the therapeutic index (peak concentration was measured at 28mg/L), but AUC was appropriate. This case describes acyclovir pharmacokinetics during CKRT in a pediatric patient treated by acyclovir. The patient was treated with adapted exposure with the usual dosing, but lower dosing should be investigated with complementary studies. ClinicalTrials.gov NCT02539407.