Drugs in R&D · 2004
Solifenacin demonstrates high absolute bioavailability in healthy men.
Клиническое исследованиеСтатьяРандомизированное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Kuipers Mirjam E, Krauwinkel Walter J J, Mulder Hans, Visser Nico
Аннотация
OBJECTIVE: Solifenacin succinate (YM905; Vesicare) is a promising new bladder selective muscarinic receptor antagonist under investigation for the treatment of overactive bladder. This study was designed to assess the absolute bioavailability of a single oral dose of solifenacin 10 mg, which is twice the suggested starting dose.
STUDY DESIGN: Single-centre, open-label, randomised, two-period, crossover, single-dose study.
METHODS: Solifenacin was administered orally as a 10 mg dose and intravenously as a 5 mg dose. Oral and intravenous (IV) doses were divided by a washout period of > or =14 days.
STUDY PARTICIPANTS: The study group consisted of 12 healthy young men, aged 20-45 years, nine of whom completed the study.
RESULTS: The pharmacokinetic analysis comprised nine subjects. A single oral dose of solifenacin 10 mg had a high absolute bioavailability of 88.0% (95% confidence interval 75.8, 102.1), low clearance (9.39 L/h [SD 2.68]), and an extensive mean volume of distribution at steady state (599L [SD 86]). Only 7% of solifenacin was excreted intact in the urine. Single oral and IV administration of solifenacin was well tolerated in this study. The most common adverse events related to drug treatment were headache and somnolence.
CONCLUSIONS: Pharmacokinetic analyses of single oral and IV doses of solifenacin demonstrated that the drug has a high absolute oral availability of 88%. This finding suggests that solifenacin may have a higher and less variable bioavailability than other antimuscarinic agents.
STUDY DESIGN: Single-centre, open-label, randomised, two-period, crossover, single-dose study.
METHODS: Solifenacin was administered orally as a 10 mg dose and intravenously as a 5 mg dose. Oral and intravenous (IV) doses were divided by a washout period of > or =14 days.
STUDY PARTICIPANTS: The study group consisted of 12 healthy young men, aged 20-45 years, nine of whom completed the study.
RESULTS: The pharmacokinetic analysis comprised nine subjects. A single oral dose of solifenacin 10 mg had a high absolute bioavailability of 88.0% (95% confidence interval 75.8, 102.1), low clearance (9.39 L/h [SD 2.68]), and an extensive mean volume of distribution at steady state (599L [SD 86]). Only 7% of solifenacin was excreted intact in the urine. Single oral and IV administration of solifenacin was well tolerated in this study. The most common adverse events related to drug treatment were headache and somnolence.
CONCLUSIONS: Pharmacokinetic analyses of single oral and IV doses of solifenacin demonstrated that the drug has a high absolute oral availability of 88%. This finding suggests that solifenacin may have a higher and less variable bioavailability than other antimuscarinic agents.