Lack of Effect of Gastric Acid-Reducing Agents on the Pharmacokinetics of Lopinavir/Ritonavir in HIV-Infected Patients

Abstract

Recent studies have shown that coadministration of certain protease inhibitors (PIs) with gastric acid-reducing agents results in decreased plasma concentrations of the PI. To assess the effect of acid-reducing agents on lopinavir/ritonavir, data from two clinical trials (n = 38 and 190) were pooled. Both trials randomized antiretroviral-naïve, HIV-infected patients to receive lopinavir/ritonavir 400/100 mg twice-daily or 800/200 mg once-daily in combination with stavudine and lamivudine, or tenofovir and emtricitabine. Concurrent administration of gastric acid-reducing agents including antacids of various brand names, proton pump inhibitors (omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole), and H(2)-receptor antagonists (ranitidine, famotidine, cimetidine, and nizatidine) was reported in both trials. Lopinavir and ritonavir pharmacokinetic parameters were evaluated. Thirty subjects were considered users of acid-reducing agents at the times of pharmacokinetic evaluation. HIV-infected patients who received gastric acid-reducing agents during administration of lopinavir/ritonavir-based treatment regimens did not appear to have a reduction in lopinavir or ritonavir exposures.

The Effect of Acid Reduction With a Proton Pump Inhibitor on the Pharmacokinetics of Lopinavir or Ritonavir in HIV‐Infected Patients on Lopinavir/Ritonavir‐Based Therapy

“…The present study was designed to evaluate formal pharmacokinetic data regarding the coadministration of LPV/r and omeprazole. The results are consistent with previous data concerning drug concentrations of lopinavir and ritonavir when coadministered with various acid‐reducing agents 14 . These findings are reassuring for patients who take acid‐reducing agents with LPV/r.…”

“…Because of their chemical nature, neither of these 2 compounds is expected to be affected by the coadministration of acid‐suppressing agents. Chiu et al 14 published data on the concurrent administration of various gastric acid‐suppressing agents (both proton pump inhibitors [PPIs] and H2 blockers) as a secondary analysis of a randomized control trial evaluating different dosing schedules for LPV/r. As part of that study, participants had trough concentrations of both ritonavir and lopinavir drawn throughout the study.…”

Effects of Acid‐Reducing Agents on the Pharmacokinetics of Lopinavir/Ritonavir and Ritonavir‐Boosted Atazanavir

“…Similar pharmacokinetics of LPV were observed after coadministration of LPV/r 400/100 mg bid with ranitidine or omeprazole compared with those after LPV/r alone. 25 In the previous retrospective analysis, trough levels of LPV and RTV were similar in patients with or without acid-reducing agent administration. Similarly, no significant differences were observed in LPV exposure after coadministration of omeprazole or ranitidine in subjects receiving LPV/r 800/200 mg qd.…”

A pharmacokinetic study of etravirine (TMC125) co‐administered with ranitidine and omeprazole in HIV–negative volunteers

“…Antiretroviral agents with a pH‐dependent solubility and gastric absorption such as atazanavir showed significant decreases of plasma concentrations when co‐administered with acid‐reducing agents, despite boosting with low‐dose ritonavir [6, 7]. No clinically significant interaction was observed when omeprazole or ranitidine was co‐administered with boosted indinavir [8], fosamprenavir [6, 9], darunavir [10], tipranavir [11] or lopinavir [12–14]. Conversely, exposure to boosted saquinavir increased substantially when co‐administered with omeprazole 40 mg q.d., regardless of whether the drugs were administered simultaneously or 2 h apart [15, 16].…”