Effect of Milk Thistle on the Pharmacokinetics of Darunavir-Ritonavir in HIV-Infected Patients
Por:
Molto, J, Valle, M, Miranda, C, Cedeno, S, Negredo, E, Clotet, B
Publicada:
1 jun 2012
Resumen:
The aim of this open-label, fixed-sequence study was to investigate the potential of the botanical supplement milk thistle (silymarin) to interact with the boosted protease inhibitor combination darunavir-ritonavir. Fifteen HIV-infected patients receiving antiretroviral therapy with darunavir-ritonavir (600/100 mg twice daily) for at least 4 weeks were included. Silymarin (150 mg every 8 h) was added to the antiretroviral treatment from days 1 to 14. Darunavir concentrations in plasma were determined by high-performance liquid chromatography immediately before and 1, 2, 4, 6, 8, 10, and 12 h after a morning dose of darunavir-ritonavir on day 0 and darunavir-ritonavir plus silymarin on day 14. Individual darunavir pharmacokinetic parameters were calculated by noncompartmental analysis and compared between days 0 and 14 by means of the geometric mean ratio (GMR) and its 90% confidence interval (CI). The median age was 48 years (interquartile range, 44 to 50 years), and the median body weight was 70 kg (interquartile range, 65 to 84 kg). Silymarin was well tolerated, and all participants completed the study. The GMRs for darunavir coadministered with silymarin relative to darunavir alone were 0.86 (90% CI, 0.70 to 1.05) for the area under the concentration-time curve from 0 to 12 h, 0.83 (90% CI, 0.80 to 0.98) for the maximum concentration, and 0.94 (90% CI, 0.73 to 1.19) for the concentration at the end of the dosing interval. In summary, coadministration of silymarin with darunavir-ritonavir seems to be safe in HIV-infected patients; no dose adjustment for darunavir-ritonavir seems to be necessary.
Filiaciones:
Molto, J:
Hosp Badalona Germans Trias & Pujol, HIV Clin, Lluita Sida Fdn, Badalona, Spain
Univ Autonoma Barcelona, E-08193 Barcelona, Spain
Valle, M:
Univ Autonoma Barcelona, E-08193 Barcelona, Spain
Inst Recerca HSCSP IIB St Pau, Barcelona, Spain
Miranda, C:
Hosp Badalona Germans Trias & Pujol, HIV Clin, Lluita Sida Fdn, Badalona, Spain
Cedeno, S:
Hosp Badalona Germans Trias & Pujol, HIV Clin, IrsiCaixa Fdn, Badalona, Spain
Negredo, E:
Hosp Badalona Germans Trias & Pujol, HIV Clin, Lluita Sida Fdn, Badalona, Spain
Clotet, B:
Hosp Badalona Germans Trias & Pujol, HIV Clin, Lluita Sida Fdn, Badalona, Spain
Univ Autonoma Barcelona, E-08193 Barcelona, Spain
Hosp Badalona Germans Trias & Pujol, HIV Clin, IrsiCaixa Fdn, Badalona, Spain
Green Published, Bronze
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