Pharmacokinetics of Rifabutin in Japanese HIV-Infected Patients with or without Antiretroviral TherapyReportar como inadecuado




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Objective

Based on drug-drug interaction, dose reduction of rifabutin is recommended when co-administered with HIV protease inhibitors for human immunodeficiency virus HIV-associated mycobacterial infection. The aim of this study was to compare the pharmacokinetics of rifabutin administered at 300 mg-day alone to that at 150 mg every other day combined with lopinavir-ritonavir in Japanese patients with HIV-mycobacterium co-infection.

Methods

Plasma concentrations of rifabutin and its biologically active metabolite, 25-O-desacetyl rifabutin were measured in 16 cases with HIV-mycobacterial coinfection. Nine were treated with 300 mg-day rifabutin and 7 with 150 mg rifabutin every other day combined with lopinavir-ritonavir antiretroviral therapy ART. Samples were collected at a median of 15 days range, 5–63 of rifabutin use.

Results

The mean Cmax and AUC0–24 of rifabutin in patients on rifabutin 150 mg every other day were 36% and 26% lower than on 300 mg-day rifabutin, while the mean Cmax and AUC0–24 of 25–O-desacetyl rifabutin were 186% and 152% higher, respectively. The plasma concentrations of rifabutin plus its metabolite were similar between the groups within the first 24 hours, but it remained low during subsequent 24 to 48 hours under rifabutin 150 mg alternate day dosing.

Conclusion

Rifabutin dose of 150 mg every other day combined with lopinavir-ritonavir seems to be associated with lower exposure to rifabutin and its metabolite compared with rifabutin 300 mg-day alone in Japanese patients. Further studies are needed to establish the optimal rifabutin dose during ART. The results highlight the importance of monitoring rifabutin plasma concentration during ART.

Trial registration

UMIN-CTR https:-upload.umin.ac.jp-cgi-open-bin-ctr-ctr.cgi?function=searchandaction=inputandlanguage=E UMIN000001102



Autor: Junko Tanuma , Kazumi Sano, Katsuji Teruya, Koji Watanabe, Takahiro Aoki, Haruhito Honda, Hirohisa Yazaki, Kunihisa Tsukada, Hiro

Fuente: http://plos.srce.hr/



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