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Lopinavir/r Reduces Levels of Rifabutin

May/June 2011

This preliminary study investigated rifabutin and LM565 (25 O desacetyl rifabutin) exposures in 14 HIV/TB coinfected patients starting LPV/r (400/100 mg twice-daily) and rifabutin (150 mg 3 times weekly). Control values for rifabutin alone (300 mg once-daily) were obtained prior to starting LPV/r. Control values for LPV/r alone were obtained 10 weeks after stopping rifabutin. Pharmacokinetic parameters (median, range) are shown in the Table 1.

Rifabutin AUC was below the target of 4.5 µg.h/ml in 42% of patients at week 2 of therapy and in 28% of patients at week 6 of therapy. The change in LM565 AUC was significantly greater than the change in rifabutin AUC. When given with LPV/r, rifabutin 150 mg three times weekly may result in low rifabutin concentrations.

Table 1: Rifabutin, LM565 and Lopinavir Levels Administered Separately and Together

  Rifabutin alone Rifabutin + LPV/r week 2 Rifabutin + LPV/r week 6 LPV/r alone
Median (range) Rifabutin
AUC 0-24h (g.h/mL) 330 (106-1950) 4.2 (1.9-5.5) 2.4 (1.3-6.4)  
Ctrough (ng/mL) 91 (11-152) 87 (20-104) 42 (8-114)  
Cmax (ng/mL) 330 (106-1950) 309 (106-564) 239 (151-526)  
Median (range) LM565
AUC 0-24h (g.h/mL) 0.7 (0.18-2.4) 1.6 (0.35-2.6) 1.6 (0.79-2.4)  
Ctrough (ng/mL) 4 (3-10) 33 (10-71) 30 (13-75)  
Cmax (ng/mL) 52 (32-72) 115 (90-190) 122 (40-221)  
Median (range) LPV
AUC 0-24h (g.h/mL)   143 (86-278) 137 (47-303) 124 (75-139)
Ctrough (ng/mL)   10 (5.6-20) 8.8 (1-17.6) 7.8 (5.1-9)
Cmax (ng/mL)   14.4 (9.2-34) 16.3 (15.4-33) 13.7 (7.8-20.9)


This study highlights the importance of the active metabolite when rifabutin is given with LPV/r.


  1. Cusato M et al. Pharmacokinetic evaluation of rifabutin and its active metabolite LM565 coadministered with lopinavir/r in HIV infected patients. 12th International Workshop on Clinical Pharmacology of HIV Therapy, 13–15 April 2011, Miami. Oral abstract: O_14.

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