Effects of omeprazole on plasma levels of raltegravir

The safety, tolerability and pharmacokinetics of raltegravir alone and in combination with omeprazole were studied in 14 healthy volunteers. Subjects received a single dose of raltegravir (400 mg) alone or 2 h after omeprazole (20 mg once daily for 4 days).

Coadministration increased raltegravir AUC by 3.12-fold, Cmax by 4.15-fold and Cmin by 1.46-fold. As the increase in Cmin was relatively minor and there was no significant change in half-life, the increase in exposure is likely due to an increase in gastric pH increasing the solubility and, absorption and bioavailability of raltegravir rather than an effect on the metabolism or clearance of raltegravir.

Although omeprazole increased raltegravir exposure by 3-4-fold in healthy subjects, exploratory pharmacokinetic data in HIV+ subjects demonstrated a reduced effect. Evaluation of the safety profile in HIV+ patients receiving acid reducing agents has not identified any areas of concern and therefore the authors indicate that the data support the use of raltegravir in patients receiving acid reducing agents with no dosage adjustment. Further investigation is needed to determine i) the pharmacokinetics of raltegravir with acid reducing agents in HIV+ patients and ii) the PK-PD relationship of raltegravir.