Background:  Acid-reducing agents, including proton pump inhibitors (eg, omeprazole) and H₂ antagonists (eg, ranitidine), are used extensively by HIV-infected patients and decrease bioavailability of some ART agents. The effect of acid-reducing agents on lopinavir/ritonavir (LPV/r) in any formulation has not been formally assessed, and the influence of decreased stomach acidity on drug bioavailability from a novel melt-extrusion LPV/r tablet is unknown. We determined the effect of omeprazole and ranitidine on the pharmacokinetics of LPV/r tablet administered once or twice daily and atazanavir (ATV) boosted by ritonavir (RTV) capsule.

Methods:  We randomized 71 healthy (HIV^­) adults to receive LPV/r tablets 400/100 mg twice daily or 800/200 mg once daily or RTV capsule 100 mg + ATV 300 mg once daily from study day 1 to 15, approximately 30 minutes after a meal. Either omeprazole 40 mg once daily was administered 1 hour before breakfast on study days 11 to 15 or ranitidine 150 mg was administered 1 hour before breakfast on study day 11. Serial blood samples were collected during a dosing interval (for 12 or 24 hours after dosing) on study days 10, 11, and 15. The pharmacokinetic parameters of LPV, RTV, and ATV were compared with and without omeprazole or ranitidine using point estimates and 90% confidence intervals.

Results:  The comparison of LPV and RTV pharmacokinetics with and without omeprazole or ranitidine for LPV/r is shown in the table. As previously shown, ATV levels were significantly decreased, but RTV levels were unchanged with administration of ATV + RTV with omeprazole or ranitidine.

Conclusions:  Acid-reducing agents do not significantly alter LPV or RTV exposure after co-administration with LPV/r 400/100 mg twice daily or 800/200 mg once daily or with RTV 100 mg twice daily. Drug bioavailability from a novel melt-extrusion LPV/r tablet is not altered by acid reducing agents.