Pharmacokinetics of lamivudine in subjects receiving peritoneal dialysis in end‐stage renal failure

This is the authors' abstract. We don't add key points for this paper.

What is already known about this subject • Prior to the conduct of this study, information on the pharmacokinetics of lamivudine in subjects with renal impairment was limited to patients on haemodialysis. (Br J Clin Pharmacol 1998; 46: 21–7). • No pharmacokinetic data were available on subjects receiving lamivudine who were concurrently receiving peritoneal dialysis. • With increasing numbers of individuals opting for peritoneal dialysis, the need to establish if dose modification was necessary in this setting was important to ensure efficacious and safe drug exposures were being obtained. What this study adds • This study demonstrated that similar to patients receiving haemodialysis, dose modifications based on reductions in renal function (i.e. decreased CLCR), also applied to subjects on peritoneal dialysis. Aims To establish whether peritoneal dialysis (PD) requires dosing modification from the CLCR‐corrected lamivudine dose in end‐stage renal failure subjects. Methods This was an open‐label cohort study. A total of 12 subjects undergoing PD, six continuous ambulatory peritoneal dialysis (CAPD) and six automated peritoneal dialysis (APD), for at least 3 months received lamivudine 10 mg (5 mg ml −1 × 2 ml) daily for 8 consecutive days, followed by an intensive pharmacokinetic assessment. Urine and dialysate were collected from 0 to 24 h postdose on day 8 where possible. Pharmacokinetic parameters were calculated using noncompartmental techniques. Results The plasma pharmacokinetic results demonstrated that peritoneal dialysis clearance (CLD) of lamivudine was similar between APD and CAPD patients with median (range) of 0.19 l h−1 (0.14–0.25) and 0.1 l h−1 (0.09–0.25), respectively. CLD was approximately 1/15th to 1/30th of plasma clearance, demonstrating that peritoneal dialysis does not contribute significantly to overall lamivudine clearance in this patient population. The AUC(0,24 h) of lamivudine given 10 mg daily to APD and CAPD patients was 3430 ng ml−1 h and 3469 ng ml−1 h, respectively, similar to historical data obtained in patients with normal renal function administered at the normal dose of 100 mg daily (3781 ng ml−1 h). There were no clinically significant changes in any safety assessments that were attributable to lamivudine. Conclusions ESRD patients who receive CAPD or APD require no supplemental dosing. These patients should follow the standard dosing reduction for patients infected with HIV or HBV with renal dysfunction.