Pharmacokinetic interaction of rifapentine and raltegravir in healthy volunteers

Abstract

Objectives: Latent tuberculosis infection and tuberculosis disease are prevalent worldwide. However, antimycobacterial rifamycins have drug interactions with many antiretroviral drugs. We evaluated the effect of rifapentine on the pharmacokinetic properties of raltegravir.

Methods: In this open-label, fixed-sequence, three-period study, 21 healthy volunteers were given: raltegravir alone (400 mg every 12 h for 4 days) on days 1-4 of Period 1; rifapentine (900 mg once weekly for 3 weeks) on days 1, 8 and 15 of Period 2 and raltegravir (400 mg every 12 h for 4 days) on days 12-15 of Period 2; and rifapentine (600 mg once daily for 10 scheduled doses) on days 1, 4-8 and 11-14 of Period 3 and raltegravir (400 mg every 12 h for 4 days) on days 11-14 of Period 3. Plasma raltegravir concentrations were measured. ClinicalTrials.gov database: NCT00809718.

Results: In 16 subjects who completed the study, coadministration of raltegravir with rifapentine (900 mg once weekly; Period 2) compared with raltegravir alone resulted in the geometric mean of the raltegravir AUC from 0 to 12 h (AUC0-12) being increased by 71%; the peak concentration increased by 89% and the trough concentration decreased by 12%. Coadministration of raltegravir with rifapentine in Period 3 did not change the geometric mean of the raltegravir AUC0-12 or the peak concentration, but it decreased the trough concentration by 41%. Raltegravir coadministered with rifapentine was generally well tolerated.

Conclusions: The increased raltegravir exposure observed with once-weekly rifapentine was safe and tolerable. Once-weekly rifapentine can be used with raltegravir to treat latent tuberculosis infection in patients who are infected with HIV.

Keywords: HIV; antiretroviral therapy; integrase strand transfer inhibitor; latent tuberculosis infection; rifamycin.

Figures

Figure 1.

Study design to evaluate the effect of rifapentine on the pharmacokinetic properties of raltegravir.

Figure 2.

Relation between raltegravir plasma concentration (arithmetic mean ± SEM) and time. Sampling was carried out after the seventh dose of raltegravir (400 mg every 12 h) in each period of the study and after the morning dose of rifapentine had been given (Periods 2 and 3). In Period 1 (open squares), raltegravir was given alone, without rifapentine. In Period 2 (filled triangles), raltegravir was given with rifapentine (900 mg once weekly). In Period 3 (filled inverted triangles), raltegravir was given with rifapentine (600 mg once daily for 5 of 7 days a week).