Pharmacokinetics and bioavailability of bemoradan, a long-acting inodilator in healthy males.
Bemoradan is a potent, long-acting orally active inodilator. The pharmacokinetics and bioavailability of bemoradan were studied in twelve normal males following oral administration of single, ascending doses of the bemoradan HCL salt in capsules. Plasma and urine levels of bemoradan were determined by HPLC (detection limits: approximately 0.5 ng/ml for plasma and 5 ng/ml for urine). Bemoradan was rapidly absorbed from the capsule formulation at all doses (Cmax occurred at 2.1-2.4 hours). Bemoradan was slowly eliminated from the body (harmonic mean t1/2 16-23 hours). There was a dose-proportional increase in the AUC (0-48) values of bemoradan in humans following the administration of 0.5, 1, 1.5 and 2 mg of bemoradan. The AUC (0-48) values increased to 2.3, 3.4 and 4.0 times when the dose was increased to 2, 3 and 4 times. Urinary excretion of unchanged bemoradan accounted for approximately 5-12% of the dose. Results from this study and previous studies in rats and dogs indicate that bemoradan is well and rapidly absorbed after oral dosing, has linear pharmacokinetics and long elimination half-lives across species.
Huang
S M
SM
RWJ Pharmaceutical Research Institute, Raritan, NJ.
Brusser
L
L
Chien
S C
SC
Simon
D
D
Smith
I L
IL
Abrams
L S
LS
Lasseter
K
K
D000284:Administration, Oral; D000328:Adult; D048588:Benzoxazines; D001682:Biological Availability; D002316:Cardiotonic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D010078:Oxazines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D011724:Pyridazines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D014665:Vasodilator Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D048588:Benzoxazines; D002316:Cardiotonic Agents; D010078:Oxazines; D011724:Pyridazines; D014665:Vasodilator Agents; C062457:bemoradan