Pharmacokinetics of rifabutin in Japanese HIV-infected patients with or without antiretroviral therapy.
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.


CONCLUSIONS
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.


BACKGROUND
UMIN-CTR (https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=search&action=input&language=E) UMIN000001102.
AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan. jtanuma@acc.ncgm.go.jp
Junko
J
Tanuma
Kazumi
K
Sano
Katsuji
K
Teruya
Koji
K
Watanabe
Takahiro
T
Aoki
Haruhito
H
Honda
Hirohisa
H
Yazaki
Kunihisa
K
Tsukada
Hiroyuki
H
Gatanaga
Yoshimi
Y
Kikuchi
Shinichi
S
Oka
D000328:Adult; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D061466:Lopinavir / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D017828:Rifabutin / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019438:Ritonavir / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult
D017320:HIV Protease Inhibitors; D017828:Rifabutin; D061466:Lopinavir; D019438:Ritonavir