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Prucalopride has a low pharmacokinetic interaction potential. It is extensively excreted unchanged in urine (approximately 60% of the dose) via both passive filtration and active renal transporters (P-gp and BCRP) and in vitro metabolism is very slow. Although 7 different metabolites are known, the most abundant of these in plasma, R107504 (formed by O-demethylation and oxidation of the resulting alcohol function to a carboxylic acid) represents 0-1.7% of the plasma total radioactivity AUC0-24.
Prucalopride did not inhibit specific CYP450 activities in in vitro studies in human liver microsomes at therapeutically relevant concentrations. Prucalopride is a weak substrate for P-glycoprotein (P-gp). Prucalopride is a weak in vitro inhibitor of P-gp and BCRP transporters, and it is not a significant inhibitor of OATP1B1, OATP1B3, OAT1, OAT3, BSEP and MRP2 transporters.
Effects of prucalopride on pharmacokinetics of other drugs: Prucalopride co-administration increased erythromycin Cmax by 40% and AUC24h by 28%. The mechanism for this interaction is not clear. The effect is not regarded as being clinically significant.
Prucalopride had no clinically relevant effects on the pharmacokinetics of warfarin, digoxin, alcohol, paroxetine or oral contraceptives.
Effects of other drugs on pharmacokinetics of prucalopride: Ketoconazole (200 mg twice/day), a potent inhibitor of CYP3A4 and of P-gp, increased the systemic exposure to prucalopride by approximately 40%. This effect is too small to be clinically relevant. Interactions of similar magnitude may be expected with other potent inhibitors of P-gp such as verapamil, cyclosporine A, and quinidine.
Therapeutic doses of probenecid, cimetidine, erythromycin and paroxetine did not affect the pharmacokinetics of prucalopride.
Effect of food: Interactions with food have not been observed.
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