Department of Nephrology, Pitié Salpétrière Hospital, Paris, France
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 insufficiency [1,2]. However, no study is available on the influence of continuous ambulatory peritoneal dialysis (CAPD) on the pharmacokinetics 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 0.5; 1; 1.5; 2; 2.5; 3; 3.5; 4; 5; 6; 8 and 10 h after oral administration of the first 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 ml/min respectively. The pharmacokinetic parameters of nevirapine were not modified 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 ml/min respectively.
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Comment.
Our data suggest that renal impairment and CAPD have no influence on the pharmacokinetics of ritonavir 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 fluid (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.
References