PHARMACOKINETICS AND BIOAVAILABILITY OF BEMORADAN, A LONG-ACTING INODILATOR IN HEALTHY-MALES

Bemoradan is a potent, long-acting orally active inodilator. The pharm acokinetics and bioavailability of bemoradan were studied in twelve no rmal males following oral administration of single, ascending doses of the bemoradan HCL salt in capsules. Plasma and urine levels of bemora dan were determined,by HPLC (detection limits: similar to 0.5 ng/ml fo r plasma and 5 ng/ml for urine). Bemoradan was rapidly absorbed from t he capsule formulation at all doses (C-max occurred at 2.1-2.4 hours). Bemoradan was slowly eliminated from the body (harmonic mean t(1/2) 1 6-23 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. Urinar y excretion of unchanged bemoradan accounted for approximately 5-12% o f the dose. Results from this study and previous studies in rats and d ogs indicate that bemoradan is well and rapidly absorbed after oral do sing, has linear pharmacokinetics and long elimination half-lives acro ss species.