A pharmacokinetic study of etravirine (TMC125) co‐administered with ranitidine and omeprazole in HIV–negative volunteers.
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Study Design
In an open‐label, randomized, one‐way, three‐period crossover trial, HIV‐negative volunteers randomly received a single dose of 100 mg etravirine alone (treatment A); 11 days of 150 mg ranitidine b.i.d. (treatment B); and 11 days of 40 mg omeprazole q.d. (treatment C). A single dose of 100 mg etravirine was co‐administered on day 8 of sessions 2 and 3. Each session was separated by a 14‐day wash‐out.
Study Results
Nineteen volunteers (seven female) participated. When a single dose of etravirine was administered in the presence of steady‐state ranitidine, etravirine least squares means ratios (90% confidence interval) for AUClast and Cmax were 0.86 (0.76, 0.97) and 0.94 (0.75, 1.17), respectively, compared with administration of etravirine alone. When administered with steady‐state omeprazole, these values were 1.41 (1.22, 1.62) and 1.17 (0.96, 1.43), respectively. Co‐administration of a single dose of etravirine and ranitidine or omeprazole was generally safe and well tolerated.
Study Conclusions
Ranitidine slightly decreased etravirine exposure, whereas omeprazole increased it by approximately 41%. The increased exposure of etravirine when co‐administered with omeprazole is attributed to CYP2C19 inhibition. Considering the favourable safety profile of etravirine, these changes are not clinically relevant. Etravirine can be co‐administered with proton pump inhibitors and H2 antagonists without dose adjustments.
References
Scholler-Gyure M, Kakuda TN, De Smedt G, Vanaken H, Bouche MP, Peeters M, Hoetelmans RM. A pharmacokinetic study of etravirine (tmc125) co‐administered with ranitidine and omeprazole in hiv–negative volunteers. British Journal Of Clinical Pharmacology. 2008; 4: 508-516.
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