Open-Label Study of the Safety and Pharmacokinetics of Solifenacin in Subjects With Hepatic Impairment
| Autor: | Mirjam E. Kuipers, Walter Krauwinkel, Timothy J. Hoon, Ronald A. Smulders |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Solifenacin Succinate Quinuclidines medicine.medical_specialty Time Factors Adolescent Metabolic Clearance Rate Cmax Urology Administration Oral Muscarinic Antagonists Urine Pharmacology Severity of Illness Index Pharmacokinetics Open label study Tetrahydroisoquinolines medicine Humans Aged Aged 80 and over Solifenacin business.industry Liver Diseases Hepatic impairment lcsh:RM1-950 Middle Aged medicine.disease lcsh:Therapeutics. Pharmacology Overactive bladder Area Under Curve Molecular Medicine Female business Follow-Up Studies Half-Life medicine.drug |
| Zdroj: | Journal of Pharmacological Sciences, Vol 102, Iss 4, Pp 405-412 (2006) |
| ISSN: | 1347-8648 1347-8613 |
| Popis: | Determining the pharmacokinetics and safety of solifenacin succinate, a once-daily, oral antimuscarinic agent indicated for treatment of overactive bladder, in subjects with hepatic impairment. In this open-label study, 16 subjects (eight with moderate hepatic impairment [defined as a Child-Pugh score of 7 – 9], eight healthy) received a single oral 10 mg solifenacin dose. Blood and urine were collected for pharmacokinetic assessments. Pharmacokinetic parameters (primary: area under the plasma concentration-time curve from time 0 to infinity [AUC0–∞] and maximum plasma concentration [Cmax]) and safety were evaluated for solifenacin and its metabolites. There were no clinically relevant differences in safety. Moderate hepatic impairment increased AUC0–∞ by 60%, and the mean elimination half-life of solifenacin and several of its metabolites was longer versus healthy subjects. Mean Cmax values were comparable between the groups. A single oral dose of solifenacin was well tolerated in hepatically impaired and healthy subjects; however, moderate hepatic impairment influenced solifenacin pharmacokinetics. In patients with mild hepatic impairment, solifenacin may be used without special caution; however, in patients with moderate hepatic impairment, doses greater than 5 mg are not recommended and the 5 mg dose should be used with caution. Keywords:: hepatic impairment, overactive bladder, pharmacokinetics, safety and tolerability, solifenacin |
| Databáze: | OpenAIRE |
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