Pharmacokinetics of once-daily trospium chloride 60 mg extended release and twice-daily trospium chloride 20 mg in healthy adults.
The objective of this study is to characterize the steady-state pharmacokinetics and compare the relative bioavailability of the extended-release capsule formulation of the antimuscarinic trospium chloride, developed for once-daily administration, and trospium chloride immediate-release tablets. This is a single-center, multidose, randomized, open-label, 2-period, 2-arm crossover, bioavailability study in healthy adult male and female subjects who are within 20% of their ideal body weight. Subjects receive trospium 60-mg extended-release capsules once daily and trospium 20-mg tablets twice daily for 10 days, each in a crossover manner. Twenty-four subjects are enrolled in the study. With multiple dosing of trospium 60 mg extended-release once daily versus 20 mg twice daily, lower geometric least squares mean area under the concentration-time curve from 0 to 24 hours (17 360 vs 28 590 pg.h/mL; ratio 61%; 90% confidence interval, 51-72) and maximum plasma concentration (1517 vs 2502 pg/mL; 61%; 90% confidence interval, 49-75) are observed. Furthermore, with trospium 60 mg extended-release versus 20 mg, median time to maximum plasma concentration is later (5.0 vs 4.5 hours) and half-life is longer (35.8 vs 27.2 hours). Trospium exposure is lower with multiple dosing of trospium 60 mg extended-release compared with trospium 20 mg twice daily. Thus, with the extended-release formulation, trospium concentrations are less likely to reach the threshold where adverse events may sometimes occur.
Silver
Nova
N
Endo Pharmaceuticals, Inc, Lexington, MA 02421, USA. silver.nova@endo.com
Sandage
Bobby
B
Sabounjian
LuAnn
L
Schwiderski
Ute
U
Shipley
James
J
Harnett
Mark
M
D000293:Adolescent; D000328:Adult; D001561:Benzilates; D001682:Biological Availability; D002214:Capsules; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009662:Nortropanes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010276:Parasympatholytics / Q000008:administration & dosage / Q000493:pharmacokinetics; D013607:Tablets; D055815:Young Adult
D001561:Benzilates; D002214:Capsules; D003692:Delayed-Action Preparations; D009662:Nortropanes; D010276:Parasympatholytics; D013607:Tablets; C003330:trospium chloride