Lopinavir/ritonavir pharmacokinetics, efficacy, and safety in HIV and hepatitis B or C coinfected adults without symptoms of hepatic impairment
OBJECTIVE: Lopinavir/ritonavir plus nucleoside reverse transcriptase inhibitors is one standard antiretroviral therapy regimen, both in patients with HIV alone and coinfected with hepatitis B or C. Our objective was to investigate whether hepatitis coinfection without clinical signs of hepatic impairment is a cofactor altering lopinavir pharmacokinetics and influencing therapy outcome.
METHODS: Steady-state 12-hour pharmacokinetic profiles of lopinavir/ritonavir were assessed in patients with (group 1, n = 20) or without (group 2, n = 36) hepatitis coinfection, taking lopinavir/ritonavir 400/100 mg twice a day plus nucleoside reverse transcriptase inhibitors, measured by means of high-performance liquid chromatography-tandem mass spectrometry. Demographic (sex, age, weight), pharmacological (formulation, comedication), clinical, and virological/immunologic parameters (HIV-RNA PCR, CD4(+) cell count) were compared between the groups and included in regression analyses for correlations with lopinavir pharmacokinetic parameters (C(min), C(max), AUC, CL, and t(1/2)) and viral load evolution over 48 weeks on therapy. Patient pairs were matched 1:2 for the parameters sex, age, weight, ethnicity, and drug formulation.
RESULTS: None of the hepatitis-related cofactors (aspartate aminotransferase, alanine aminotransferase, γGT, HBe Ag, HBsAg, HCV-RNA PCR, HCV-therapy) had an influence on lopinavir pharmacokinetics in this group of patients. Lopinavir C(min) (P = 0.039) and area under the curve (P = 0.038) and ritonavir C(max) (P = 0.049) were significantly enhanced in hepatitis-coinfected patients, but correlated only with drug formulation (ie, soft gel capsule or Meltrex tablet formulation, multivariate regression analysis, P = 0.001), not hepatitis coinfection.
CONCLUSIONS: Despite moderately enhanced lopinavir/ritonavir plasma concentrations, regular therapeutic drug monitoring is not to be considered in hepatitis-coinfected patients without hepatic impairment. Antiviral efficacy is comparable between both groups, a less-pronounced CD4(+) cell increase in hepatitis-coinfected patients is in line with previously published data.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:36 |
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| Enthalten in: |
Therapeutic drug monitoring - 36(2014), 2 vom: 17. Apr., Seite 192-201 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Khaykin, Pavel [VerfasserIn] |
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| Links: |
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| Themen: |
2494G1JF75 |
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| Anmerkungen: |
Date Completed 09.02.2015 Date Revised 17.03.2014 published: Print Citation Status MEDLINE |
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| doi: |
10.1097/FTD.0b013e3182a28c6a |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM236430629 |
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| 100 | 1 | |a Khaykin, Pavel |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Lopinavir/ritonavir pharmacokinetics, efficacy, and safety in HIV and hepatitis B or C coinfected adults without symptoms of hepatic impairment |
| 264 | 1 | |c 2014 | |
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| 500 | |a Date Revised 17.03.2014 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: Lopinavir/ritonavir plus nucleoside reverse transcriptase inhibitors is one standard antiretroviral therapy regimen, both in patients with HIV alone and coinfected with hepatitis B or C. Our objective was to investigate whether hepatitis coinfection without clinical signs of hepatic impairment is a cofactor altering lopinavir pharmacokinetics and influencing therapy outcome | ||
| 520 | |a METHODS: Steady-state 12-hour pharmacokinetic profiles of lopinavir/ritonavir were assessed in patients with (group 1, n = 20) or without (group 2, n = 36) hepatitis coinfection, taking lopinavir/ritonavir 400/100 mg twice a day plus nucleoside reverse transcriptase inhibitors, measured by means of high-performance liquid chromatography-tandem mass spectrometry. Demographic (sex, age, weight), pharmacological (formulation, comedication), clinical, and virological/immunologic parameters (HIV-RNA PCR, CD4(+) cell count) were compared between the groups and included in regression analyses for correlations with lopinavir pharmacokinetic parameters (C(min), C(max), AUC, CL, and t(1/2)) and viral load evolution over 48 weeks on therapy. Patient pairs were matched 1:2 for the parameters sex, age, weight, ethnicity, and drug formulation | ||
| 520 | |a RESULTS: None of the hepatitis-related cofactors (aspartate aminotransferase, alanine aminotransferase, γGT, HBe Ag, HBsAg, HCV-RNA PCR, HCV-therapy) had an influence on lopinavir pharmacokinetics in this group of patients. Lopinavir C(min) (P = 0.039) and area under the curve (P = 0.038) and ritonavir C(max) (P = 0.049) were significantly enhanced in hepatitis-coinfected patients, but correlated only with drug formulation (ie, soft gel capsule or Meltrex tablet formulation, multivariate regression analysis, P = 0.001), not hepatitis coinfection | ||
| 520 | |a CONCLUSIONS: Despite moderately enhanced lopinavir/ritonavir plasma concentrations, regular therapeutic drug monitoring is not to be considered in hepatitis-coinfected patients without hepatic impairment. Antiviral efficacy is comparable between both groups, a less-pronounced CD4(+) cell increase in hepatitis-coinfected patients is in line with previously published data | ||
| 650 | 4 | |a Controlled Clinical Trial | |
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| 650 | 7 | |a Lopinavir |2 NLM | |
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| 650 | 7 | |a Ritonavir |2 NLM | |
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| 700 | 1 | |a Kotzerke, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Stephan, Christoph |e verfasserin |4 aut | |
| 700 | 1 | |a Nisius, Gabi |e verfasserin |4 aut | |
| 700 | 1 | |a Bickel, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Haberl, Annette |e verfasserin |4 aut | |
| 700 | 1 | |a Stürmer, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Kurowski, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Brodt, Reinhard |e verfasserin |4 aut | |
| 700 | 1 | |a von Hentig, Nils |e verfasserin |4 aut | |
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