It is contraindicated by the manufacturer to administer boceprevir with potent CYP3A4/5 inducers that could cause a considerable reduction in plasma concentrations and ultimately reduced efficacy of boceprevir. The results of this study were not predicted based on the known pharmacology of these drugs; boceprevir concentrations were expected to be reduced by etravirine, via induction of CYP3A, and etravirine concentrations were expected to increase via inhibition of CYP3A. Extreme caution and increased monitoring should be employed if boceprevir and etravirine must be co-administered.
Etravirine versus Boceprevir
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Study Design
In a recent study completed by Hammond, et al1, twenty healthy subjects were given boceprevir, etravirine, or the combination of the two for eleven to fourteen days in an open label crossover design. Pharmacokinetic sampling occurred between days eleven and fourteen of each sequence. Geometric mean ratios (GMRs) and 90% confidence interval (CI) for the combination versus each drug alone were evaluated using 2 one-sided t tests. The hypothesis of equivalence was rejected if 90% GMR CI was not contained in the interval (0.8-1.25).
Study Results
Geometric Mean Ratios (90% CI) for etravirine AUCo,t, Cmax, and Cmin were 0.77 (0.66 to 0.91), 0.76 (0.68 to 0.85), and 0.71 (0.54 to 0.95), respectively, in combination versus alone. Boceprevir GMRs (90% CI) for AUCo,t, Cmax, and C8 were 1.10 (0.94 to 1.28), 1.10 (0.94 to 1.29), and 0.88 (0.66 to 1.17), respectively, in combination versus alone. Etravirine AUCo,t, Cmax, and Cmin decreased 23%, 24%, and 29%, respectively, with boceprevir. Boceprevir AUC0,t and Cmax increased 10% and C8 decreased 12% by etravirine. The authors concluded that a complex interplay between CYP3A inhibition and alterations in efflux transporter protein action, as well as a displacement of etravirine protein binding by boceprevir, may have led to these results.
References
Kyle P Hammond, Pamela Wolfe, James R Burton Jr, Julie A Predhomme, Christine M Ellis, Michelle L Ray, Lane R Bushman, Jennifer J Kiser. Pharmacokinetic interaction between boceprevir and etravirine in hiv/hcv seronegative volunteers. Jaids Journal Of Acquired Immune Deficiency Syndromes. 2013; 1: 67-73.
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