Coadministration of rifampicin dramatically reduces plasma lopinavir (LPV) concentrations. In healthy volunteers, doubling the dose of lopinavir-ritonavir (LPV/r) capsules overcame this interaction, but a subsequent study of double doses of the tablets was stopped early owing to hepatotoxicity. However, healthy-volunteer study findings may not apply to HIV-positive adults.
This study evaluated the steady-state pharmacokinetics of LPV in HIV-infected adults stable on LPV/r tablets (400/100 mg twice daily) who were given rifampicin (600 mg daily), and the dose of the LPV/r gradually increased over a period of two weeks (first to 600/150 twice daily and then to 800/200 mg twice daily). Twenty-one subjects started the study, but two were withdrawn due to grade 3/4 transaminitis.
The median (IQR) pre-dose LPV concentrations were 8.1 (6.2 to 9.8) mg/L at baseline, 1.7 (0.3 to 3.0) mg/L after 7 days of rifampicin, 5.9 (2.1 to 9.9) mg/L with 1.5 times the dose of LPV/r, and 10.8 (7.0 to 13.1) mg/L with double-dose LPV/r. There were no significant differences in the LPV AUC, Cmax, pre-dose concentrations, 12-hour concentration, or half-life between the baseline and double-dose LPV/r time points.
Doubling the dose of the tablet formulation of LPV/r overcame induction by rifampicin, with less hepatotoxicity occurring in this cohort of HIV-infected participants than reported in healthy-volunteer studies. The cohort consisted of HIV-infected patients who were virologically suppress with high CD4 counts -- the risk of hepatotoxicity may be different in HIV-infected individuals with TB and/or with different CD4 counts.
Source: hiv-druginteractions.org (28 June 2011).
Ref: Decloedt EH et al. Pharmacokinetics of lopinavir in HIV-infected adults receiving rifampin with adjusted doses of lopinavir-ritonavir tablets. Antimicrob Agents Chemother, 2011, 55(7): 3195-3200.
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