Pharmacokinetics of single, oral-dose voriconazole in peritoneal dialysis patients

Background: Voriconazole is a new triazole antifungal drug. Its pharmacokinetics and transfer to peritoneal dialysate in peritoneal dialysis (PD) patients have not been studied. Methods: Five patients with end-stage renal disease requiring support by PD were administered a single dose of 200 mg of voriconazole orally. Plasma and peritoneal dialysate were collected for measurement of voriconazole concentrations at times 1, 2, 4, and 24 hours. Results: Voriconazole was absorbed and achieved maximum concentration (C_max) in plasma at mean time 2.4 ± 0.7 (SE) hours. Time to C_max in dialysate was 2.8 ± 0.5 hours. Mean C_max for plasma was 0.55 ± 0.20 μg/mL, and for dialysate, approximately half that of plasma (0.25 ± 0.09 μg/mL). The dialysate to plasma ratio of voriconazole was 0.66 ± 0.11. Less than 1% of the administered voriconazole dose (1.3 ± 0.2 mg) was recovered in dialysate 24 hours after dosing. Conclusion: Voriconazole penetrates well into peritoneal fluid. There is minimal peritoneal clearance of voriconazole; therefore, no dosage adjustment is needed for patients on PD therapy.

Index words:  Fungal peritonitis , peritoneal dialysis (PD) , pharmacokinetics , peritoneal clearance , bioavailability