The pharmacokinetics and tolerability of oseltamivir suspension in patients on haemodialysis and continuous ambulatory peritoneal dialysis.

Background: Oseltamivir dose reduction is recommended for patients with end-stage renal disease (ESRD). However, dosing recommendations are not available for treatment or prophylaxis of influenza in these patients. This study assessed the pharmacokinetics and tolerability of oseltamivir in ESRD patients undergoing maintenance haemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD).

Methods: In this open-label, multiple-dose study, patients received 30 mg oral oseltamivir suspension over 6.5 weeks. This dose was predicted to be suitable for ESRD patients based on a 2-compartment model. HD patients received 9 doses given 1 h after the completion of alternate HD sessions (three times a week). CAPD patients received 6 doses given once weekly after a dialysate exchange. The primary parameters were peak plasma concentration (C(max)) and the area under the curve (AUC) for oseltamivir and oseltamivir carboxylate.

Results: In HD patients, the C(max) for oseltamivir carboxylate after single and repeated dosing were 943 and 1120 ng/ml, respectively. The mean AUC(0-42) was 31 600 ng h/ml for days 1-5 and 38 200 ng h/ml for days 38-43. Similarly, in CAPD patients, mean C(max) after the first and sixth doses were 885 and 849 ng/ml, respectively. The mean AUC(0-48) values for days 1-6 and days 36-43 were 33 400 and 32 400 ng h/ml, respectively. Oseltamivir was well-tolerated in both the patient groups.

Conclusions: A 30 mg dose of oseltamivir given once weekly in CAPD or after alternate sessions in HD patients provides sufficient exposure to oseltamivir carboxylate to allow safe and effective anti-influenza treatment and prophylaxis.