Pharmacokinetics of bepridil and two 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 disease (ESRD) before and after hemodialysis. Patients underwent dialysis 1 day after a single oral 200-mg dose of bepridil hydrochloride; blood was sampled for up to 7 days. The mean (+/- SD) peak plasma concentration, time of peak concentration, and area under the plasma concentration-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 micrograms.h/mL; McN-A-2600, 57 +/- 16 ng/mL, 4.2 +/- 2.0 hours, 0.53 +/- 0.29 microgram.h/mL; McN-6303, 284 +/- 120 ng/mL, 4.7 +/- 1.5 hours, 4.06 +/- 1.11 micrograms.h/mL. The bepridil area under the curve corrected for dose was similar to that in healthy volunteers, suggesting that plasma clearance was unaffected by severe renal impairment. None of the compounds were removed by dialysis, and no rebound in plasma concentrations was observed after the end of dialysis. The disposition of bepridil appears to be unchanged in patients with ESRD; and is unaffected by hemodialysis. Thus, no dosage adjustment will be required for ESRD patients and those receiving hemodialysis with cuprophane filters.
Awni
W M
WM
Drug Evaluation Unit, Hennepin County Medical Center, Minneapolis, MN 55404, USA.
Halstenson
C E
CE
Nayak
R K
RK
Opsahl
J A
JA
Desiraju
R K
RK
Minn
F L
FL
Matzke
G R
GR
D000284:Administration, Oral; D000328:Adult; D015764:Bepridil / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D008875:Middle Aged; D006435:Renal Dialysis
C095304:McN 6303; C095303:McN A 2600; D015764:Bepridil