Darifenacin pharmacokinetics

Details regarding the pharmacokinetics, contraindica-tions/precautions, and dosing of the five recommended agents (oxybutynin, tolterodine, trospium chloride, solifenacin, and darifenacin) are illustrated in Table 50-3.7 12,14 16 A current clinical controversy is which of these agents should be considered first-line in UUI, and in the case of oxybutynin and... 

T. Kerbusch, U. Walby, P. A. Milligan, and M. O. Karlsson, Population pharmacokinetic modelling of darifenacin and its hydroxylated metabolite using pooled data, incorporating saturable first-pass metabolism, CYP2D6 genotype and formulation-dependent bioavaUabihty. Br J Clin Pharmacol 56 639-652 (2003). 

Kerbusch, T., Milligan, P.A., and Karlsson, M.O. Assessment of the relative in vivo potency of the hydroxylated metabolite of darifenacin in its ability to decrease salivary flow using pooled population pharmacokinetic-pharmacodynamic data. British Journal of Clinical Pharmacology 2003 57 170-180. 

Solifenacin did not alter the pharmacokinetics or effect of warfarin. Similarly, darifenacin did not alter the prothrombin time in response to warfarin. 

Darifenacin increased digoxin exposure by a modest 16%, which would usually not be clinically important. Solifenacin did not ai-ter the pharmacokinetics of digoxin. 

Skerjanec A. The clinical pharmacokinetics of darifenacin. Clin Pharmacokinet (2006) 45, 325-50. 

Paroxetine and cimetidine cause small, clinically irrelevant, increases in darifenacin levels. Darifenacin increases imipramine levels, and caution is required with this and other tricyclics. Darifenacin does not significantly affect the pharmacokinetics of midazolam or combined oral contraceptives. 

The manufacturers note that steady-state darifenacin 10 mg three times daily had no effect on the pharmacokinetics of a combined oral contraceptive (ethinylestradiol/levonorgestrel) in a study in 22 healthy women. 

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