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.

Provided by

This article was provided by HIV i-Base. It is a part of the publication HIV Treatment Bulletin. Visit HIV i-Base's website to find out more about their activities, publications and services.

No comments have been made.

Add Your Comment:
(Please note: Your name and comment will be public, and may even show up in
Internet search results. Be careful when providing personal information! Before
adding your comment, please read's Comment Policy.)

Your Name:

Your Location:

(ex: San Francisco, CA)

Your Comment:

Characters remaining:


The content on this page is free of advertiser influence and was produced by our editorial team. See our content and advertising policies.