PHARMACOKINETICS OF BEPRIDIL AND 2 OF ITS METABOLITES IN PATIENTS WITH END-STAGE RENAL-DISEASE

The pharmacokinetics of bepridil and 2 of its major metabolites (McN-A -2600 and McN-6303) were studied in 6 patients with end-stage renal di sease (ESRD) before and after hemodialysis. Patients underwent dialysi s 1 day after a single oral 200-mg dose of bepridil hydrochloride; blo od was sampled for up to 7 days. The mean (+/-SD) peak plasma concentr ation, rime of peak concentration, and area under the plasma concentra tion-time curve (0-168 hours) for each agent were as follows: bepridil , 806 +/- 321 ng/mL, 2.6 +/- 1.6 hours, 4.87 +/- 1.21 mu g . h/mL; McN -A-2600, 57 +/- 16 ng/mL, 4.2 +/- 2.0 hours, 0.53 +/- 0.29 mu g . h/mL ; McN-6303, 284 +/- 120 ng/mL, 4.7 +/- 1.5 hours, 4.06 +/- 1.11 mu g . h/ml. The bepridil area under the curve corrected for dose was simila r to that in healthy volunteers, suggesting that plasma clearance was unaffected by severe renal impairment. None of the compounds were remo ved by dialysis, and no rebound in plasma concentrations was observed after the end of dialysis. The disposition of bepridil appears to be u nchanged in patients with ESRD; and is unaffected by hemodialysis. Thu s, no dosage adjustment will be required for ESRD patients and those r eceiving hemodialysis with cuprophane filters.