PHARMACOKINETICS OF R(-TERODILINE GIVEN INTRAVENOUSLY AND ORALLY TO HEALTHY-VOLUNTEERS())

(+)-Terodiline was given orally (25 mg) and intravenously (12.5 mg) to eight healthy volunteers. The pharmacokinetics of (+)-terodiline coul d be described by a one compartment model. The lag time of absorption was 0.6 +/- 0.5 hr (mean +/- S.D.), the absorption half-life 0.9 +/- 0 .5 hr, the time to maximum serum concentration 5.6 +/- 2.2 hr and the corresponding maximum serum concentration 62 +/- 22 mug/l. The volume of distribution was found to be 372 +/- 84 1, the systemic clearance 8 6 + 29 ml /min., the mean residence time 81 +/- 38 hr and the observed terminal half-life of elimination 56 +/- 26 hr. The urinary excretion of the intravenous dose was 12 +/- 6% and the renal clearance 10 +/- 5 ml/min. The bioavailability of (+)-terodiline was 93 +/- 19%. The pr esent results indicate that (+)-terodiline as well as the racemate can be characterized as low clearance long half-life drugs. One subject w as a poor hydroxylator of debrisoquine and exhibited a 3-fold decrease in clearance and increase in half-life of (+)-terodiline relative to extensive metabolizers. Observed pharmacological effects were mild acc omodation disturbances and dry mouth, i.e. the same effects as those t hat may be seen at a corresponding dose of terodiline given as a racem ic mixture.