Lopinavir/r reduces levels of rifabutin
1 May 2011. Related: Conference reports, Antiretrovirals, PK and drug interactions, PK Workshop 12th 2011.
HIV-druginteractions.org
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.
| 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) | |
comment
This study highlights the importance of the active metabolite when rifabutin is given with LPV/r.
Reference:
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.