TY - JOUR
T1 - Lopinavir pharmacokinetic profiles in HIV-infected patients during rifabutin-based anti-mycobacterial therapy
AU - Matteelli, Alberto
AU - Villani, Paola
AU - Carvalho, Anna Cristina C
AU - El-Hamad, Issa
AU - Cusato, Maria
AU - Apostoli, Alessandra
AU - Marcantoni, Claudio
AU - Calabresi, Alessandra
AU - Dal zoppo, Sarah
AU - Bigoni, Sara
AU - Regazzi, Mario
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
KW - Antiretroviral therapy
KW - Drug interactions
KW - Treatment
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U2 - 10.1093/jac/dks218
DO - 10.1093/jac/dks218
M3 - Article
C2 - 22678727
AN - SCOPUS:84866622613
SN - 0305-7453
VL - 67
SP - 2470
EP - 2473
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
IS - 10
M1 - dks218
ER -