Purpose of the study
To investigate the potential of a commonly used botanical supplement, Echinacea purpurea, to interact with the boosted protease inhibitor darunavir/ritonavir.
Methods
Open-label, fixed-sequence study in 15 HIV-infected patients receiving antiretroviral therapy including darunavir/ritonavir (600/100 mg twice daily) for at least 4 weeks. Echinacea purpurea root extract-containing capsules were added to the antiretroviral treatment (500 mg every 6 hours) from days 1 to 14. Darunavir concentrations in plasma were determined by using HPLC immediately before and 1, 2, 4, 6, 8, 10 and 12 hours after a morning dose of darunavir/ritonavir on days 0 (darunavir/ritonavir) and 14 (darunavir/ritonavir + echinacea). Individual darunavir pharmacokinetic parameters were calculated by using non-compartmental analysis, and were compared between days 0 and 14 by using the geometric mean ratio (GMR) and its 95% confidence interval (95% CI).
Results
Median (range) age was 49 (43-67) years, and body mass index was 24.2 (18.7-27.5) kg/m2. Echinacea was well tolerated and all participants completed the study. Relative to administration of darunavir/ritonavir alone, its coadministration with Echinacea purpurea resulted in little change in darunavir pharmacokinetic parameters. Table 1
Table 1.
| DRV/r | DRV/r + Echinacea | GMR (95% CI) | p | |
|---|---|---|---|---|
| Cτ (ng/mL) | 2.1 (1.6-2.7) | 1.7 (1.4-2.2) | 0.84 (0.59-1.19) | 0.311 |
| AUCτ (ng.h/mL) | 46.2 (39.0-54.7) | 41.6 (35.1-49.2) | 0.90 (0.71-1.14) | 0.374 |
| Cmax (ng/mL) | 6.4 (5.5-7.4) | 6.2 (5.3-7.25) | 0.98 (0.79-1.21) | 0.810 |
Conclusions
coadministration of Echinacea purpurea with darunavir/ritonavir was safe and well tolerated in HIV-infected patients; data suggest that no dose adjustment for darunavir/ritonavir is necessary.