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Pharmacokinetic interaction between the hcv protease inhibitor boceprevir and cyclosporine and tacrolimus in healthy volunteers
Hepatology, 05/14/2012
Clinical Article
Hulskotte E et al. – Dose adjustments of cyclosporine should be anticipated when administered with boceprevir, guided by close monitoring of cyclosporine blood concentrations and frequent assessments of renal function and cyclosporine–related side effects. Concomitant administration of boceprevir with tacrolimus requires significant dose reduction and prolongation of the dosing interval for tacrolimus, with close monitoring of tacrolimus blood concentrations and frequent assessments of renal function and tacrolimus–related side effects.
Methods- This 2-part, open-label, fixed-sequence, pharmacokinetic interaction study evaluated boceprevir with cyclosporine (part 1) and tacrolimus (part 2).
- In part 1, 10 subjects received single-dose cyclosporine (100 mg) on day 1, single-dose boceprevir (800 mg) on day 3, and concomitant cyclosporine/boceprevir on day 4.
- After washout, subjects received boceprevir (800 mg TID) for 7 days plus single-dose cyclosporine (100 mg) on day 6.
- In part 2A, 12 subjects received single-dose tacrolimus (0.5 mg).
- After washout, they received boceprevir (800 mg TID) for 11 days plus single-dose tacrolimus (0.5 mg) on day 6.
- In part 2B, 10 subjects received single-dose boceprevir (800 mg) and 24 hours later boceprevir (800 mg) plus tacrolimus (0.5 mg).
- Coadministration of boceprevir with cyclosporine/tacrolimus was well tolerated.
- Concomitant boceprevir increased the AUCinf and Cmax of cyclosporine with geometric mean ratios (GMRs) [90% CI] of 2.7 [2.4, 3.1] and 2.0 [1.7, 2.4], respectively.
- Concomitant boceprevir increased the AUCinfand Cmax of tacrolimus with GMRs [90% CI] of 17 [14, 21] and 9.9 [8.0, 12], respectively.
- Neither cyclosporine nor tacrolimus coadministration had a meaningful effect on boceprevir pharmacokinetics.
