Pharmacokinetic profile of OPC-8212 in humans: a new, nonglycosidic, inotropic agent.

OPC-8212, a new inotropic agent, was administered orally as a single 7.5-, 15-, 30-, 60-, 120-, or 240-mg dose in a sequentially ascending order to 21 male healthy volunteers to determine the pharmacokinetic profile. Each volunteer received one of the six doses after an overnight fast. After the single-dose study was completed and the safety and tolerability were ascertained, 3 of the 21 volunteers participated in a 15-day repeated-dose (30 mg once daily) study to determine the steady-state kinetic profile. The AUC0-infinity and Cmax values were proportional to doses (mg or mg/kg, P less than .001). The mean elimination t1/2, apparent oral clearance (CL/F) and percentage fraction of dose excreted unchanged in urine up to 336 hours postdose (fe0-336) appeared to be comparable among the six single doses examined. The overall mean (+/- SEM) kinetic parameters obtained from the 21 subjects were: 44.7 +/- 1.2 hours for t1/2, 0.284 +/- 0.018 L/hr or 4.49 +/- 0.28 mL/hr/kg for CL/F, and 17.7 +/- 0.9% for fe0-336. A steady state of the drug appeared to be attained by about day 9 after the initiation of the repeated dosing: the mean postdose 2- and 24-hour plasma drug concentrations observed during days 9 to 15 ranged from 6.3 +/- 0.5 micrograms/mL to 6.9 +/- 0.6 micrograms/mL and from 3.6 +/- 0.7 micrograms/mL to 4.0 +/- 0.6 micrograms/mL, respectively. The mean fraction of the daily dose excreted unchanged in urine over the dosing interval (fe0-r) during days 9 to 15 ranged from 19.2 +/- 1.4% to 25.6 +/- 0.6%.(ABSTRACT TRUNCATED AT 250 WORDS)