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: AUC0-12, 187.5, 161.8 and 121.1 μg h/mL; Ctrough, 13.2, 10.0 and 7.7 μg/mL; Cmax, 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 Ctrough and AUC0-12 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. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Lopinavir pharmacokinetic profiles in HIV-infected patients during rifabutin-based anti-mycobacterial therapy

Matteelli A.;Marcantoni C.;Calabresi A.;Dal zoppo S.;Bigoni S.;
2012-01-01

Abstract

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: AUC0-12, 187.5, 161.8 and 121.1 μg h/mL; Ctrough, 13.2, 10.0 and 7.7 μg/mL; Cmax, 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 Ctrough and AUC0-12 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. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11379/533167
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