Pharmacokinetics of ritonavir and nevirapine in peritoneal dialysis

Sir, Hepatic clearance is the major route of elimination of ritonavir and nevirapine (-95% and 85%, respectively). Therefore it has been suggested that no dosage adjustment is necessary in patients with renal insuf®ciency w1,2x. However , no study is available on the in¯uence of continuous ambulatory peritoneal dialysis (CAPD) on the pharmaco-kinetics of ritonavir. We report on the pharmacokinetics of ritonavir and nevirapine in an HIV-1 patient on CAPD. Case. A 40-year-old man with end-stage renal disease (ESRD), had been treated for 2 years with CAPD for an HIV-associated nephropathy. He was receiving oral ritonavir 600 mg every 12 h, nevirapine 200 mg every 12 h, zidovudine 100 mg every 8 h, and didanosine 100 mg every 24 h for 2 months. Blood samples were collected just before and at 0. and 10 h after oral administration of the ®rst two drugs. Paired blood and dialysate samples were collected at the start of dialysis and every hour during 12 h. CAPD was carried out with three isotonic and one hypertonic bags per day. Pharmacokinetic parameters of our patient are summarized in Table 1. For ritonavir, pharmacokinetic parameters remained within a normal range compared with patients with normal renal function. Values of extraction ratio and dialysance were less than 1% and 3.4 mlumin respectively. The pharmacokinetic parameters of nevirapine were not modi®ed compared to those in subjects with normal renal function except for the AUC (0-`), which was increased in our patient. The values of extraction ratio and dialysance of nevirapine were 51.85% and 3.3 mlumin respectively. No side-effects were observed, in particular no diarrhoea, abdominal pain, diabetes, hyperlipidaemia or hepatic toxicity. The patient's viral load decreased to undetectable levels (-200 copiesuml). Comment. Our data suggest that renal impairment and CAPD have no in¯uence on the pharmacokinetics of rit-onavir and nevirapine. Ritonavir does not cross the peritoneal membrane because it is tightly bound to plasma protein (98%) and because of its relatively large size (720.95 Da). In contrast, a non-negligible proportion of nevirapine was recovered in the dialysis ¯uid (half that in plasma) because of a smaller molecular weight (266.3 Da) and a lower protein binding (-60%). Therefore, no dosage adjustment is necessary in patients with ESRD undergoing CAPD. Gambertoglio JG. Antiviral therapy for HIV patients with renal insuf®ciency. Table 1. Pharmacokinetic parameters of ritonavir (200 mgu12 h) and nevirapine (200 mgu12 h) in an HIV1-infected patient with end-stage renal disease …