Dose-escalating study of the pharmacokinetics and tolerability of fesoterodine in children with overactive bladder

作者：Malhotra Bimal^*; El Tahtawy Ahmed; Wang Ellen Q; Darekar Amanda; Cossons Nandini; Crook Tim J; Scholfield David; Reddy Pramod

来源：Journal of Pediatric Urology, 2012, 8(4): 336-342.

DOI：10.1016/j.jpurol.2012.02.008

• Antimuscarinic
• Neurogenic detrusor overactivity
• Fesoterodine
• 5-HMT
• Overactive bladder
• Pediatric
• Pharmacokinetics
• Tolerability

Objective: To determine the pharmacokinetics, safety and tolerability of fesoterodine, and assess the utility of 3-day bladder diaries (exploratory objective) in pediatric subjects with neurogenic detrusor overactivity or idiopathic overactive bladder (OAB).
Methods: In this 8-week open-label study, subjects (8e17 years, >25 kg) received fesoterodine 4 mg for 4 weeks, then 8 mg for 4 weeks. Blood samples were obtained at weeks 4 and 8.
Results: Of 21 subjects enrolled, 11 had neurogenic detrusor overactivity and 10 had idiopathic OAB; 1 discontinued (personal reasons). Mean age and weight were 13.2 years and 54.0 kg for boys (n = 12) and 13.1 years and 49.2 kg for girls (n = 9). 5-Hydroxy-methyltolterodine plasma concentrations did not differ by diagnosis and were consistent with predictions based on adult data. Treatment-related adverse events (all mild or moderate) included 1 event each of dry mouth, constipation, dry eyes and blurred vision, and 2 events each of nausea and increased post-void residual volume. Three-day bladder diaries proved feasible.
Conclusions: Oral administration of fesoterodine in pediatric subjects (>25 kg) with idiopathic OAB or neurogenic detrusor overactivity produced steady-state plasma 5-hydroxy-methyltolterodine exposures similar to those in adults. The doses given were well tolerated.

• 出版日期2012-8