TY - JOUR
AU - Gabrielsson, Johan
AB - Influence of CYP2D6 polymorphism on the pharmacokinetics and pharmacodynamics of tolterodine OCjectiPe: To determine whether cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of toltero- dine by investigating potential differences in pharmacokinetics and pharmacodynamics (heart rate, accom- modation, and salivation) of tolterodine and its 5-hydroxymethyl metabolite between poor metabolizers and extensive metabolizers of debrisoquin (INN, debrisoquine). Methods: Sixteen male subjects (eight extensive metabolizers and eight poor metabolizers) received 4 mg tolterodine by mouth twice a day for 8 days followed by a single intravenous infusion of 1.8 mg toltero- dine for 30 minutes after a washout period. Doses were given as the tartrate salt. The pharmacokinetics of tolterodine and 5-hydroxymethyl metabolite were determined, and the pharmacodynamics were measured. Results: The mean systemic clearance of tolterodine was significantly lower (p < 0.001) among poor metab- olizers (9.0 + 2.1 L/hr) compared with extensive metabolizers (44 * 13 L/hr), resulting in a fourfold longer elimination half-life (p < 0.001). The terminal half-life of the 5-hydroxymethyl metabolite (2.9 = 0.4 hours) was slightly longer than that of the parent compound (2.3 * 0.6 hours) among extensive metab- olizers, but the 5-hydroxymethyl metabolite was undetectable in the serum of poor metabolizers. Only 
TI - Influence of CYP2D6 polymorphism on the pharmacokinetics and pharmacodynamics of tolterodine
JF - Clinical Pharmacology & Therapeutics
DO - 10.1016/S0009-9236(98)90104-7
DA - 1998-05-01
UR - https://www.deepdyve.com/lp/wiley/influence-of-cyp2d6-polymorphism-on-the-pharmacokinetics-and-97Rwh4A05V
SP - 529
EP - 539
VL - 63
IS - 5
DP - DeepDyve
ER -