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 could 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 micrograms/l. The volume of distribution was found to be 372 +/- 84 1, the systemic clearance 86 +/- 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 present results indicate that (+)-terodiline as well as the racemate can be characterized as low clearance long half-life drugs. One subject was 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 accomodation disturbances and dry mouth, i.e. the same effects as those that may be seen at a corresponding dose of terodiline given as a racemic mixture.