OBJECTIVES: To evaluate the pharmacokinetic profile of ritonavir-boosted lopinavir in HIV-infected patients during rifabutin-based anti-mycobacterial therapy. PATIENTS AND METHODS: A longitudinal, cross-over pharmacokinetic evaluation of lopinavir with and without rifabutin in HIV-infected subjects with mycobacterial disease was done. All received lopinavir/ritonavir (400/100 mg twice a day) + an adjusted rifabutin dose of 150 mg every other day. Twelve-hour lopinavir pharmacokinetic sampling occurred at 2 weeks (T1) and 6 weeks (T2) after starting combined therapy and 10 weeks after completion of adjusted rifabutin (T3). Plasma was assayed using an HPLC method; lopinavir plasma concentration-time data were analysed using non-compartmental methods. RESULTS: In 10 patients with complete lopinavir curves at T1, T2 and T3 pharmacokinetic values were, respectively: AUC(0-12), 187.5, 161.8 and 121.1 μg · h/mL; C(trough), 13.2, 10.0 and 7.7 μg/mL; C(max), 18.7, 15.9 and 13.3 μg/mL; and apparent oral clearance (CL/F), 0.035, 0.037 and 0.045 L/h/kg. Lopinavir C(trough) and AUC(0-12) were significantly higher at T1 compared with T3 while CL/F remained unchanged throughout. Combined treatment was well tolerated and none of the patients experienced moderate to severe lopinavir-related adverse events. CONCLUSIONS: Lopinavir serum concentrations are not reduced when the drug is administered together with an adjusted dose of 150 mg of rifabutin every other day.
OBJECTIVES: To evaluate the pharmacokinetic profile of ritonavir-boosted lopinavir in HIV-infectedpatients during rifabutin-based anti-mycobacterial therapy. PATIENTS AND METHODS: A longitudinal, cross-over pharmacokinetic evaluation of lopinavir with and without rifabutin in HIV-infected subjects with mycobacterial disease was done. All received lopinavir/ritonavir (400/100 mg twice a day) + an adjusted rifabutin dose of 150 mg every other day. Twelve-hour lopinavir pharmacokinetic sampling occurred at 2 weeks (T1) and 6 weeks (T2) after starting combined therapy and 10 weeks after completion of adjusted rifabutin (T3). Plasma was assayed using an HPLC method; lopinavir plasma concentration-time data were analysed using non-compartmental methods. RESULTS: In 10 patients with complete lopinavir curves at T1, T2 and T3 pharmacokinetic values were, respectively: AUC(0-12), 187.5, 161.8 and 121.1 μg · h/mL; C(trough), 13.2, 10.0 and 7.7 μg/mL; C(max), 18.7, 15.9 and 13.3 μg/mL; and apparent oral clearance (CL/F), 0.035, 0.037 and 0.045 L/h/kg. Lopinavir C(trough) and AUC(0-12) were significantly higher at T1 compared with T3 while CL/F remained unchanged throughout. Combined treatment was well tolerated and none of the patients experienced moderate to severe lopinavir-related adverse events. CONCLUSIONS:Lopinavir serum concentrations are not reduced when the drug is administered together with an adjusted dose of 150 mg of rifabutin every other day.
Authors: Richard A Murphy; Vincent C Marconi; Rajesh T Gandhi; Daniel R Kuritzkes; Henry Sunpath Journal: PLoS One Date: 2012-09-28 Impact factor: 3.240
Authors: Henri Gautier Ouedraogo; Alberto Matteelli; Giorgia Sulis; Tegwinde Rebeca Compaore; Serge Diagbouga; Simon Tiendrebeogo; Alberto Roggi; Kadari Cisse; Pier Francesco Giorgetti; Paola Villani; Lassana Sangare; Jacques Simpore; Mario Regazzi; Seni Kouanda Journal: Ann Clin Microbiol Antimicrob Date: 2020-01-22 Impact factor: 3.944