Study of the Population Pharmacokinetic Characteristics of Once-Daily Trospium Chloride 60 mg Extended-Release Capsules in Patients with Overactive Bladder and in Healthy Subjects

• Published in: Clinical drug investigation 2013-02, Vol.33 (2), p.133-141
• Main Authors: Harnett, Mark D., Shipley, James, MacLean, Laura, Schwiderski, Ute, Sandage, Bobby W.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Area Under Curve; Benzilates - administration & dosage; Benzilates - pharmacokinetics; Benzilates - therapeutic use; Body Surface Area; Case-Control Studies; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Delayed-Action Preparations; Female; Humans; Internal Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Models, Biological; Muscarinic Antagonists - administration & dosage; Muscarinic Antagonists - pharmacokinetics; Muscarinic Antagonists - therapeutic use; Nonlinear Dynamics; Nortropanes - administration & dosage; Nortropanes - pharmacokinetics; Nortropanes - therapeutic use; Original Research Article; Pharmacology/Toxicology; Pharmacotherapy; Time Factors; Urinary Bladder, Overactive - drug therapy; Young Adult
• ISSN: 1173-2563; 1179-1918
• DOI: 10.1007/s40261-012-0039-8

Background Overactive bladder is a common disorder that affects approximately 34 million adults in the United States. Anticholinergic (antimuscarinic) agents are the most widely used pharmacological option for overactive bladder. Objective This study set out to identify and characterize the influence of a number of intrinsic characteristics on the pharmacokinetics of the anticholinergic agent trospium chloride (Sanctura ® ) 60 mg extended release (XR), and to evaluate the correlation between trospium chloride exposure and key efficacy and safety outcomes in subjects and patients. Study Design Pharmacokinetic data were obtained from three studies in which a total of 349 subjects received trospium chloride XR for up to 12 weeks. Plasma trospium chloride concentration data were pooled and a population pharmacokinetic model was derived using non-linear mixed-effects modelling. Demographic factors were assessed for influence on the model. The correlation between trospium chloride exposure and key efficacy variables was evaluated. Correlations between exposure and safety outcomes were also assessed. Intervention Trospium chloride XR 60 mg once daily for 10 days in healthy volunteers or trospium chloride 60 mg XR once daily for either 2 weeks or 12 weeks in patients with overactive bladder. Results The best population pharmacokinetic model was determined to be a two-compartment model with zero-order release into the depot compartment and first-order absorption. Body surface area (BSA) was the only covariate to significantly ( P