Effects of the H2-receptor antagonist famotidine on the pharmacokinetics of atazanavir-ritonavir with or without tenofovir in HIV-infected patients
Significant pharmacokinetic interactions can result between acid-suppressing agents and some protease inhibitors (PIs) in the management of HIV infection. In healthy subjects, famotidine, an H(2)-receptor antagonist, reduces exposures of atazanavir by 4-28% at doses of 20-40 mg twice daily. This study evaluated the effect of famotidine 20-40 mg twice daily on the pharmacokinetics of atazanavir/ritonavir 300/100 mg once daily with and without tenofovir disoproxil fumarate (TDF) 300 mg in HIV-infected patients (n=40; 87.5% male; mean age 42, range 26-63 years; 55% white). Coadministration of famotidine 40 mg and atazanavir/ritonavir to HIV-infected patients reduced exposures of atazanavir by approximately 20%. This is comparable to reductions seen in HIV-uninfected subjects. Coadministration of famotidine 20 mg had less impact on atazanavir exposures, with no reduction of atazanavir geometric mean plasma concentration at 24 h postdose (C(min)). In the presence of TDF, administration of famotidine 20-40 mg twice daily 2 h after and 10 h before atazanavir/ritonavir reduced exposures of atazanavir by 19-25%. However, all individual atazanavir C(min) values remained at least five-fold above the population mean protein-binding adjusted 90% maximum effect (EC(90)) against wild-type HIV (14 ng/mL). No viral load rebound was observed at end of study. The results confirmed that coadministration of an H(2)-receptor antagonist with atazanavir/ritonavir in HIV-infected patients resulted in similar magnitude of reductions in atazanavir exposures as in healthy subjects. This supports the current dose recommendations for coadministration of an H(2)-receptor antagonist with atazanavir/ritonavir.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2011 |
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| Erschienen: |
2011 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
|---|---|
| Enthalten in: |
AIDS patient care and STDs - 25(2011), 9 vom: 24. Sept., Seite 509-15 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Xiaodong [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.03.2012 Date Revised 20.10.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1089/apc.2011.0113 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM210064749 |
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| 100 | 1 | |a Wang, Xiaodong |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effects of the H2-receptor antagonist famotidine on the pharmacokinetics of atazanavir-ritonavir with or without tenofovir in HIV-infected patients |
| 264 | 1 | |c 2011 | |
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| 500 | |a Date Completed 28.03.2012 | ||
| 500 | |a Date Revised 20.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Significant pharmacokinetic interactions can result between acid-suppressing agents and some protease inhibitors (PIs) in the management of HIV infection. In healthy subjects, famotidine, an H(2)-receptor antagonist, reduces exposures of atazanavir by 4-28% at doses of 20-40 mg twice daily. This study evaluated the effect of famotidine 20-40 mg twice daily on the pharmacokinetics of atazanavir/ritonavir 300/100 mg once daily with and without tenofovir disoproxil fumarate (TDF) 300 mg in HIV-infected patients (n=40; 87.5% male; mean age 42, range 26-63 years; 55% white). Coadministration of famotidine 40 mg and atazanavir/ritonavir to HIV-infected patients reduced exposures of atazanavir by approximately 20%. This is comparable to reductions seen in HIV-uninfected subjects. Coadministration of famotidine 20 mg had less impact on atazanavir exposures, with no reduction of atazanavir geometric mean plasma concentration at 24 h postdose (C(min)). In the presence of TDF, administration of famotidine 20-40 mg twice daily 2 h after and 10 h before atazanavir/ritonavir reduced exposures of atazanavir by 19-25%. However, all individual atazanavir C(min) values remained at least five-fold above the population mean protein-binding adjusted 90% maximum effect (EC(90)) against wild-type HIV (14 ng/mL). No viral load rebound was observed at end of study. The results confirmed that coadministration of an H(2)-receptor antagonist with atazanavir/ritonavir in HIV-infected patients resulted in similar magnitude of reductions in atazanavir exposures as in healthy subjects. This supports the current dose recommendations for coadministration of an H(2)-receptor antagonist with atazanavir/ritonavir | ||
| 650 | 4 | |a Clinical Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Anti-HIV Agents |2 NLM | |
| 650 | 7 | |a Histamine H2 Antagonists |2 NLM | |
| 650 | 7 | |a Oligopeptides |2 NLM | |
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| 700 | 1 | |a Boffito, Marta |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jenny |e verfasserin |4 aut | |
| 700 | 1 | |a Chung, Ellen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yaoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Patterson, Kristine |e verfasserin |4 aut | |
| 700 | 1 | |a Kashuba, Angela |e verfasserin |4 aut | |
| 700 | 1 | |a Tebas, Pablo |e verfasserin |4 aut | |
| 700 | 1 | |a Child, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Mahnke, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Bertz, Richard |e verfasserin |4 aut | |
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