Pharmacokinetics, safety, and tolerability of solifenacin in patients with renal insufficiency.
To evaluate the pharmacokinetics, safety, and tolerability of solifenacin in patients with mild, moderate, or severe renal disease, eighteen patients with renal disease and six healthy volunteers received a single oral dose of solifenacin (10 mg). Pharmacokinetic parameters were assessed from blood samples drawn over a 360-h period. Safety and tolerability were also evaluated. Total mean +/- S.D. exposure (ng . h/mL) to solifenacin in healthy individuals (1190 +/- 403) was increased in patients with renal disease (mild: 1784 +/- 792, moderate: 1559 +/- 555, severe: 2530 +/- 700), and elimination half-life (mean +/- S.D. [h]) was prolonged (healthy: 68.2 +/- 27.2, mild: 89.1 +/- 34.5, moderate: 90.6 +/- 27.3, severe: 111 +/- 38.3). A significant correlation was found between creatinine clearance and pharmacokinetic parameters for exposure and apparent oral clearance. No deaths or serious adverse events occurred during the study. Solifenacin 10 mg was well tolerated in patients with renal disease. Solifenacin displays a higher exposure and a prolonged half-life in patients with renal impairment, especially severe. Therefore, while no special cautions are necessary for patients with mild/moderate renal impairment, patients with severe renal impairment should receive no more than 5 mg solifenacin once daily.
Smulders
Ronald A
RA
Astellas Pharma Europe BV, Leiderdorp, The Netherlands. ronald.smulders@eu.astellas.com
Smith
Neila N
NN
Krauwinkel
Walter J
WJ
Hoon
Timothy J
TJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000493:pharmacokinetics*; D009961:Orosomucoid / Q000378:metabolism; D011485:Protein Binding; D011812:Quinuclidines / Q000009:adverse effects / Q000493:pharmacokinetics*; D051437:Renal Insufficiency / Q000378:metabolism*; D000069464:Solifenacin Succinate; D044005:Tetrahydroisoquinolines / Q000009:adverse effects / Q000493:pharmacokinetics*
D018727:Muscarinic Antagonists; D009961:Orosomucoid; D011812:Quinuclidines; D044005:Tetrahydroisoquinolines; D000069464:Solifenacin Succinate