ROXITHROMYCIN DISPOSITION IN PATIENTS ON CONTINUOUS AMBULATORY PERITONEAL-DIALYSIS

Roxithromycin is a macrolide antibiotic with a spectrum of activity similar to erythromycin. Roxithromycin has been shown to have a favourable pharmacokinetic profile with more reliable absorption and higher, prolonged plasma and tissue concentrations compared with erythromycin. The pharmacokinetics and dialysis clearance of roxithromycin were studied in twelve patients with end-stage renal disease on continuous ambulatory perionteal dialysis. Following a single 300 mg oral dose, multiple blood, dialysate and urine samples were collected over 48 h and assayed for roxithromycin by a microbiological method. Peak plasma concentrations were attained between 0 . 5 and 5 h, and ranged from 2 . 3 to 6 . 8 mg/L. The mean elimination half-life was 20 . 6 +/- 8 . 7 h, compared with 10 to 14 h previously reported in healthy volunteers given a single 300 mg dose. Plasma clearance relative to bioavailability (Cl-p/F) ranged from 37 . 3 to 118 . 3 mL/min, The percentage of the dose recovered in the dialysate and net dialysis clearance were low, ranging from 1 . 0 to 3 . 1% and 0 . 9 to 1 . 8 mL/min, respectively. Only 1% of the dose was recovered in the urine. These results demonstrate that roxithromycin is not substantially removed by continuous ambulatory peritoneal dialysis, and its elimination is prolonged in renal failure, possibly due to impaired nonrenal elimination.