title: Effect of concomitant administration of trospium chloride extended release on the steady-state pharmacokinetics of metformin in healthy adults.
abstract: BACKGROUND
  Overactive bladder (OAB) is often associated with a number of co-morbid medical conditions, including diabetes mellitus. This may necessitate several concomitant treatments, thus creating the potential for drug-drug interactions (DDIs). Trospium is renally eliminated, not metabolized via cytochrome P450; therefore, cytochrome P450 DDIs are unlikely. However, coadministration with another renally eliminated drug (e.g., metformin) may theoretically result in a DDI.
  
  
  OBJECTIVE
  The objective of this study was to evaluate the pharmacokinetics (plasma and urine) and safety/tolerability of the coadministration of trospium chloride extended release (XR) and metformin under steady-state conditions in healthy male and female subjects.
  
  
  METHODS
  In a single-centre, randomized, open-label, two-group, two-period study in healthy males and females aged 18-45 years, 44 subjects received oral metformin 500 mg twice daily for 3.5 days during one period, and oral trospium chloride XR 60 mg once daily for 10 days, followed by trospium chloride XR 60 mg once daily for 4 days plus metformin 500 mg twice daily for 3.5 days during the other period. The two periods occurred in a crossover fashion, separated by a 3-day washout period.
  
  
  RESULTS
  Trospium chloride XR coadministration did not alter metformin steady-state pharmacokinetics. Metformin coadministration reduced trospium steady-state maximum plasma concentration (by 34 %) and area under the concentration-time curve from 0-24 hours (by 29 %). Neither drug's renal clearance was affected. No safety/tolerability issues of concern were observed with coadministration.
  
  
  CONCLUSIONS
  No dosage adjustment is necessary for metformin when coadministered with trospium chloride XR.
authors: Allergan, Inc., 2525 Dupont Drive, Irvine, CA 92612, USA.
authors: Michael G
authors: MG
authors: Oefelein
authors: Warren
authors: W
authors: Tong
authors: Sam
authors: S
authors: Kerr
authors: Kavitha
authors: K
authors: Bhasi
authors: Rina K
authors: RK
authors: Patel
authors: Dale
authors: D
authors: Yu
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001561:Benzilates / Q000494:pharmacology*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D008297:Male; D008687:Metformin / Q000493:pharmacokinetics*; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009662:Nortropanes / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D001561:Benzilates; D003692:Delayed-Action Preparations; D007004:Hypoglycemic Agents; D018727:Muscarinic Antagonists; D009662:Nortropanes; C003330:trospium chloride; D008687:Metformin