Rifabutin (RFB) 150 mg qd and 300 mg RFB TIW are both effective doses, but QD dosing may be beneficial in avoiding rifabutin associated Uveitis. LPV/r 400/100 mg BID can give adequate lopinavir levels in HIV and TB co-infected patients who were treated with RFB both 150 mg QD and 300 mg TIW. Higher concentration might result in adverse drug reactions.
Lopinavir/Ritonavir versus Rifabutin
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Study Design
In healthy volunteers, the coadministration of ritonavir-boosted lopinavir (LPV/r) with rifabutin (RBT) significantly increased RBT pharmacokinetic (PK) parameters when comparing with RBT administered alone.
Study Results
When 12 healthy, HIV-negative patients received LPV/r 400/100mg twice daily with RBT 150mg daily for 10 days, geometric mean ratios (GMRs; LPV/r +RBT/ RBT) [90% CIs] of AUC, Cmax, and Cmin for RBT were 3.03 [2.79,3.3], 2.12 [1.89, 2.38], and 4.9 [3.18, 5.76], respectively. Geometric mean ratios (GMRs; LPV/r +RBT/ RBT) [90% CIs] of active metabolite of RBT(25-O-desacetyl rifabutin) were AUC of 47.5 [29.3, 51.8], Cmax of 23.6 [13.7, 25.3], Cmin of 94.9 [74, 122].
Study Conclusions
The manufacturer of LPV/r (Kaletra®) recommended RBT dose at maximum 150 mg every other day or 3 times weekly if RBT is used concomitantly with LPV/r. However, several clinical trials in HIV/TB coinfected patients have been reported that these recommended doses (i.e.150 mg every other day or 3 times weekly) might lower plasma concentration of RBT. Some experts, including Centers for Disease Control and Prevention (CDC), recommended a RBT dosage of 150 mg once daily or 300mg 3 times/week in HIV/TB coinfected patients receiving LPV/r with RBT and also recommended that RBT plasma concentrations and antimycobacterial activity be monitored.
References
Boulanger C, Hollender E, Farrell K. Pharmacokinetic evaluation of rifabutin in combination with lopinavir-ritonavir in patients with hiv infection and active tuberculosis. Clinical Infectious Diseases. 2009; 9: 1305-1311.
Lopinavir/Ritonavir vs Rifabutin
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Study Design
This was a randomized, open-label, 2- arm, intensive pharmacokinetic study, as well as a 24 week efficacy study, conducted in Thai HIV and TB co-infected patients. A total of 21 patients were enrolled in the study. 10 patients were randomized to rifabutin (RFB) 150mg QD and 11 patients received RFB 300mg TIW. RFB pharmacokinetics were evaluated before and between weeks 2 to week 8 after co-administration of lopinavir/ritonavir (LPV/r). We used a LC-MS/MS method to determine RFB and 25-O-desacetyl RFB (desmetRFB) at Radbound university and and HPLC method to determine LPV/r concentrations
Study Results
AUC of RFB 150mg QD combined with LPV/r is moderately higher than RFB alone ( 41.9%). and AUC over 48 hours in patients with RFB 300 mg TIW combined with LPV/r is 23% higher than RFB alone. Geometric mean Cmax (CV) of RFB 150mg QD +LPV/r and 300mg QD alone were similar 0.65 mg/L versus 0.66mg/L, whereas the Cmax after RFB 300mg TIW + LPV/r was 24% higher. Exposure to desmetRFB was 1060% and 837% higher for 150mg RFB QD+LPV/r and 300mgRFB TIW+LPV/r. Overall RFB and desmetRFB exposure were 14% and 22% lower for the 300mg RFB TIW group compared to the 150mg RFB QD group. Pharmacokinetic parameters of LPV/r are in therapeutic level and were similar in both arms. Every patient in this study was cured from TB but uveitis which is associated to rifabutin developed in two patients who received RFB 300mg TIW
Study Conclusions
The authors concluded that RFB 150mg QD and 300mg TIW could result in adequate exposure in Thai patients who concurrently use LPV/r. Moreover, this study shows that LPV/r 400/100 mg BID can give adequate lopinavir levels in HIV and TB co-infected patients who were treated with RFB both 150 mg QD and 300 mg TIW.
References
Fujitnirun, C, Manosuthi, W, Gatechompol, S. Pharmacokinetics of rifabutin 150 mg qd vs 300 mg tiw with lpv/r in hiv/tb patients . Conference On Retroviruses And Opportunistic Infections. Boston. ; March 2018.
Lopinavir/Ritonavir vs Rifabutin
^
Study Design
This was a randomized, open-label, 2- arm, intensive pharmacokinetic study, as well as a 24 week efficacy study, conducted in Thai HIV and TB co-infected patients. A total of 21 patients were enrolled in the study. 10 patients were randomized to rifabutin (RFB) 150mg QD and 11 patients received RFB 300mg TIW. RFB pharmacokinetics were evaluated before and between weeks 2 to week 8 after co-administration of lopinavir/ritonavir (LPV/r). We used a LC-MS/MS method to determine RFB and 25-O-desacetyl RFB (desmetRFB) at Radbound university and and HPLC method to determine LPV/r concentrations
Study Results
AUC of RFB 150mg QD combined with LPV/r is moderately higher than RFB alone ( 41.9%). and AUC over 48 hours in patients with RFB 300 mg TIW combined with LPV/r is 23% higher than RFB alone. Geometric mean Cmax (CV) of RFB 150mg QD +LPV/r and 300mg QD alone were similar 0.65 mg/L versus 0.66mg/L, whereas the Cmax after RFB 300mg TIW + LPV/r was 24% higher. Exposure to desmetRFB was 1060% and 837% higher for 150mg RFB QD+LPV/r and 300mgRFB TIW+LPV/r. Overall RFB and desmetRFB exposure were 14% and 22% lower for the 300mg RFB TIW group compared to the 150mg RFB QD group. Pharmacokinetic parameters of LPV/r are in therapeutic level and were similar in both arms. Every patient in this study was cured from TB but uveitis which is associated to rifabutin developed in two patients who received RFB 300mg TIW
Study Conclusions
The authors concluded that RFB 150mg QD and 300mg TIW could result in adequate exposure in Thai patients who concurrently use LPV/r. Moreover, this study shows that LPV/r 400/100 mg BID can give adequate lopinavir levels in HIV and TB co-infected patients who were treated with RFB both 150 mg QD and 300 mg TIW.
References
Fujitnirun, C, Manosuthi, W, Gatechompol, S. Pharmacokinetics of rifabutin 150 mg qd vs 300 mg tiw with lpv/r in hiv/tb patients . Conference On Retroviruses And Opportunistic Infections. Boston. ; March 2018.
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