Authors: Bimal K Malhotra Penelope H Crownover Robert LaBadie Paul Glue Scott A MacDiarmid
Publish Date: 2009/11/14
Volume: 66, Issue: 2, Pages: 171-176
Abstract
Diurnal variation can affect drug pharmacokinetics Fesoterodine is a new antimuscarinic drug for the treatment of overactive bladder OAB We estimated the relative bioavailability of 5hydroxymethyl tolterodine 5HMT the active metabolite of fesoterodine following nighttime and daytime administrationIn this randomized openlabel two–period two–treatment crossover singledose study healthy subjects received daytime and nighttime oral dosing of fesoterodine 8mg sustainedrelease tablets separated by a minimum 60h washout period Blood samples for 5–HMT PK determination were collected before dosing and at specified intervals up to 48 h postdose Safety was assessed by adverse event AE reportsFourteen subjects completed the study Plasma concentration versus time profiles AUC of 5HMT were similar for daytime and nighttime dosing Mean AUC infty 5HMT values were 479 and 514 ng h/mL for nighttime and daytime dosing respectively the mean time to reach maximum concentration Cmax values were 39 and 50 ng/mL respectively Nighttime versus daytime AUC infty and Cmax ratios of 5HMT were 93 and 79 respectively 90 confidence intervals CIs indicated equivalence for AUC infty but not for Cmax The median time to reach maximum concentration Tmax was 50 h for both dosing regimens and the mean terminal elimination halflife T½ was 59 and 57 h for nighttime and daytime dosing respectively Seven treatmentrelated AEs most commonly headache occurred in five subjectsThe AUC values for daytime and nighttime administration of fesoterodine were equivalent The 21 reduction in the Cmax for nighttime dosing is unlikely to be clinically relevant No safety issues were apparent These results support both daytime and nighttime administration of fesoterodine for OAB treatment
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