Open-label study of the safety and pharmacokinetics of solifenacin in subjects with hepatic impairment.
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 [AUC(0-infinity)] and maximum plasma concentration [C(max)]) and safety were evaluated for solifenacin and its metabolites. There were no clinically relevant differences in safety. Moderate hepatic impairment increased AUC(0-infinity) by 60%, and the mean elimination half-life of solifenacin and several of its metabolites was longer versus healthy subjects. Mean C(max) 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.
Kuipers
Mirjam
M
Astellas Pharma Europe BV, Leiderdorp, The Netherlands.
Smulders
Ronald
R
Krauwinkel
Walter
W
Hoon
Timothy
T
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D005260:Female; D005500:Follow-Up Studies; D006207:Half-Life; D006801:Humans; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011812:Quinuclidines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D012720:Severity of Illness Index; D000069464:Solifenacin Succinate; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013997:Time Factors
D018727:Muscarinic Antagonists; D011812:Quinuclidines; D044005:Tetrahydroisoquinolines; D000069464:Solifenacin Succinate