Lopinavir pharmacokinetic profiles in HIV-infected patients during rifabutin-based anti-mycobacterial therapy
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2012 |
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| Erschienen: |
2012 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:67 |
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| Enthalten in: |
The Journal of antimicrobial chemotherapy - 67(2012), 10 vom: 16. Okt., Seite 2470-3 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Matteelli, Alberto [VerfasserIn] |
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| Links: |
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| Themen: |
1W306TDA6S |
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| Anmerkungen: |
Date Completed 09.01.2013 Date Revised 21.11.2013 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1093/jac/dks218 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM218452691 |
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| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Matteelli, Alberto |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Lopinavir pharmacokinetic profiles in HIV-infected patients during rifabutin-based anti-mycobacterial therapy |
| 264 | 1 | |c 2012 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 09.01.2013 | ||
| 500 | |a Date Revised 21.11.2013 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVES: To evaluate the pharmacokinetic profile of ritonavir-boosted lopinavir in HIV-infected patients during rifabutin-based anti-mycobacterial therapy | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Anti-HIV Agents |2 NLM | |
| 650 | 7 | |a Antitubercular Agents |2 NLM | |
| 650 | 7 | |a Rifabutin |2 NLM | |
| 650 | 7 | |a 1W306TDA6S |2 NLM | |
| 650 | 7 | |a Lopinavir |2 NLM | |
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| 650 | 7 | |a Ritonavir |2 NLM | |
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| 700 | 1 | |a Villani, Paola |e verfasserin |4 aut | |
| 700 | 1 | |a Carvalho, Anna Cristina C |e verfasserin |4 aut | |
| 700 | 1 | |a El-Hamad, Issa |e verfasserin |4 aut | |
| 700 | 1 | |a Cusato, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Apostoli, Alessandra |e verfasserin |4 aut | |
| 700 | 1 | |a Marcantoni, Claudio |e verfasserin |4 aut | |
| 700 | 1 | |a Calabresi, Alessandra |e verfasserin |4 aut | |
| 700 | 1 | |a Dal Zoppo, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Bigoni, Sara |e verfasserin |4 aut | |
| 700 | 1 | |a Regazzi, Mario |e verfasserin |4 aut | |
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