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.
Hallén
B
B
Department of Pharmaceutics, Kabi Pharmacia AB, Uppsala, Sweden.
Gabrielsson
J
J
Palmér
L
L
Ekström
B
B
D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D001774:Blood Chemical Analysis; D002082:Butylamines / Q000493:pharmacokinetics*; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010276:Parasympatholytics / Q000493:pharmacokinetics*; D013237:Stereoisomerism
D002082:Butylamines; D002121:Calcium Channel Blockers; D010276:Parasympatholytics; C010637:terodiline