Rabeprazole: pharmacokinetics and pharmacokinetic drug interactions

Rabeprazole is the most recently approved proton pump inhibitor in Germany. The substance has an absolute bioavailability upon oral administration of approximately 52% which is robust against food intake or administration of antacids. Maximal plasma concentrations are reached after approximately 3-4 h. Concentrations increase proportionally with the dose. Rabeprazole undergoes an almost complete, mainly non-enzymatic metabolism with renal elimination of the metabolites. CYP3A4 and CYP2C19 contribute to the fraction of metabolism mediated enzymatically. Elimination half-life is about 1 h. The extent of rabeprazole concentration increase by old age, poor metabolizer status for CYP2C19 and impairment of liver function is not greater than two-fold, impaired renal function does not affect the elimination. Even in patients with delayed elimination, no relevant accumulation of rabeprazole was observed upon long-term administration. In in vivo studies, rabeprazole had no noteworthy effect on the metabolism of other drugs. This statement however must be made with reservation because of shortcomings in published studies with respect to the methods used and presentation and because of lacking investigations about possible effects on the cytochrome P-450 enzymes CYP3A4 and CYP2D6. A slight reduction in ketoconazole absorption and a moderate increase in digoxin concentrations should be taken into account for concomitant therapy, but is expected to be clinically relevant only in isolated cases. Based on these partially incomplete data, in summary it is to be expected that rabeprazole can be administered at a standard dose for the respective disease in almost any patient for the entire duration of therapy, and that usually no dose adjustment of other drugs is required when rabeprazole is coadministered.