TY  - JOUR
AU  - Kanter, C.T.M.M. de
AU  - Colbers, A.P.
AU  - Blonk, M.I.
AU  - Wissen, C.P.W.G.M. van
AU  - Schouwenberg, B.J.J.W.
AU  - Drenth, J.P.H.
AU  - Burger, D.M.
PY  - 2013
UR  - https://hdl.handle.net/2066/118714
AB  - OBJECTIVES: Proton pump inhibitors (PPIs) can limit the solubility of concomitant drugs, which can lead to decreased absorption and exposure. Reduced efficacy can be a consequence and in the case of an antimicrobial agent this may contribute to development of resistance. Patients chronically infected with the hepatitis C virus can be treated with a boceprevir-containing regimen and it is relevant to know if interactions between PPIs and boceprevir exist. This study was designed to investigate the influence of a frequently used PPI, omeprazole, on the pharmacokinetics of boceprevir and vice versa. METHODS: In this open-label, three-period, randomized, cross-over, Phase I study, healthy subjects were randomly assigned to 40 mg of omeprazole once daily for 5 days, 800 mg of boceprevir three times daily for 5 days and 40 mg of omeprazole once daily + 800 mg of boceprevir three times daily for 5 days, or the same treatment in a different order. Every treatment was followed by a wash-out period. At day 5 of every treatment pharmacokinetic blood sampling was performed for 8 h after medication intake. ClinicalTrials.gov: NCT01470690. RESULTS: All 24 subjects (15 males) completed the study and no serious adverse events were reported. Geometric mean ratios (90% CI) of the area under the plasma concentration-time curve up to 8 h (AUC0-8) and maximum plasma concentration (Cmax) of boceprevir with omeprazole versus boceprevir alone were 0.92 (0.87-0.97) and 0.94 (0.86-1.02), respectively. For omeprazole these values were 1.06 (0.90-1.25) for AUC0-8 and 1.03 (0.85-1.26) for Cmax for the combination versus omeprazole alone. CONCLUSIONS: Omeprazole did not have a clinically significant effect on boceprevir exposure, and boceprevir did not affect omeprazole exposure.
TI  - Lack of a clinically significant drug-drug interaction in healthy volunteers between the HCV protease inhibitor boceprevir and the proton pump inhibitor omeprazole
EP  - 1422
SN  - 0305-7453
IS  - iss. 6
SP  - 1415
JF  - Journal of Antimicrobial Chemotherapy
VL  - vol. 68
DO  - https://doi.org/10.1093/jac/dkt032
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/118714/118714.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - de Kanter, C.T.
AU  - Blonk, M.I.
AU  - Colbers, A.P.
AU  - Schouwenberg, B.J.J.W.
AU  - Burger, D.M.
PY  - 2013
UR  - https://hdl.handle.net/2066/118715
AB  - BACKGROUND: Patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are likely to use both HIV and HCV treatment. Drug-drug interactions have been demonstrated between boceprevir, an HCV protease inhibitor, and frequently prescribed antiretroviral drugs, such as efavirenz and boosted HIV protease inhibitors. Concomitant administration of boceprevir with these drugs should be avoided. This study was designed to investigate the absence of a drug-drug interaction between boceprevir and raltegravir, an HIV integrase inhibitor. METHODS: This was an open-label, randomized, 2-period, crossover phase 1 trial in 24 healthy volunteers. All subjects were randomly assigned to receive boceprevir 800 mg every 8 hours for 9 days plus a single dose of raltegravir 400 mg on day 10 followed by a washout period and a single dose of raltegravir 400 mg on day 38, or the same medication in reverse order. Blood samples for pharmacokinetics were collected and pharmacokinetic parameters were calculated. RESULTS: The geometric mean (GM) of raltegravir area under the concentration-time curve (AUC)(0-12h) and maximum plasma concentration (C(max)) for raltegravir + boceprevir vs raltegravir alone were 4.27 (95% confidence interval [CI], 3.22-5.66) vs 4.04 (95% CI, 3.09-5.28) mg * hour/L and 1.06 (95% CI, .76-1.49) vs 0.93 (95% CI, .70-1.23) mg/L, respectively. GM ratio estimates of raltegravir AUC(0-12h) and C(max) for raltegravir + boceprevir vs raltegravir alone were 1.04 (90% CI, .88-1.22) and 1.11 (90% CI, .91-1.36), respectively. The GM of boceprevir AUC(0-8h), C(max), and C(8h) were 5.45 (95% CI, 5.11-5.81) mg * hour/L, 1.88 (95% CI, 1.72-2.06) mg/L, and 0.09 (95% CI, .07-.11) mg/L, respectively. These data are comparable to those from historical controls. CONCLUSIONS: Due to the absence of a clinically significant drug interaction, raltegravir can be recommended for combined HIV/HCV treatment including boceprevir. CLINICAL TRIALS REGISTRATION: NCT01288417.
TI  - Lack of a clinically significant drug-drug interaction in healthy volunteers between the hepatitis C virus protease inhibitor boceprevir and the HIV integrase inhibitor raltegravir
EP  - 306
SN  - 1058-4838
IS  - iss. 2
SP  - 300
JF  - Clinical Infectious Diseases
VL  - vol. 56
DO  - https://doi.org/10.1093/cid/cis824
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/118715/118715.pdf?sequence=1
ER  -