Safety and pharmacokinetics of lopinavir in HIV/HCV coinfected patients with advanced liver disease
PURPOSE: There are few data about the safety and pharmacokinetics of lopinavir in HIV/HCV coinfected patients with very advanced liver disease.
METHOD: Prospective study of 60 HIV/HCV coinfected patients who underwent a liver biopsy and received a lopinavir-based regimen. The rate of hepatotoxiciy and plasma trough levels were determined in absence/presence of cirrhosis (25 cases), especially in 11 patients with Child-Pugh stage B-C.
RESULTS: Overall, geometric mean level of lopi-navir was 7,109 ng/mL (interquartile range [IQR], 5,163-9,029), without differences according to cirrhosis (7,662; IQR, 5,165-10,442) or not (6,708; IQR, 5,524-8,526; P = .6). In 11 patients with Child-Pugh stage B-C, trough level was 9,640 ng/mL (IQR, 1,620-11,622 ng/mL), but there was a 99% interpatient variability (72 to 13,331 ng/mL). During a follow-up of 195.2 patient-years, there were 7 cases of hepatotox-icity, with an incidence of 3.39 episodes/100 patient-years (2.2 to 7.9). This incidence was higher in patients with Child-Pugh stage B-C (5.43 episodes/100 patient-years). There were no differences in lopinavir trough levels between patients with or without liver toxicity (7,100 vs 7,119 ng/mL; P = .9).
CONCLUSION: The risk of lopinavir-associated hepatotoxicity in patients with very advanced liver disease is low. However, lopinavir plasma trough levels are increased, and there is a high interpatient variability.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2011 |
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| Erschienen: |
2011 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
HIV clinical trials - 12(2011), 5 vom: 03. Sept., Seite 235-43 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Casado, José L [VerfasserIn] |
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| Links: |
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| Themen: |
2494G1JF75 |
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| Anmerkungen: |
Date Completed 26.01.2012 Date Revised 21.11.2013 published: Print Citation Status MEDLINE |
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| doi: |
10.1310/hct1205-235 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM213959666 |
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| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
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| 100 | 1 | |a Casado, José L |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Safety and pharmacokinetics of lopinavir in HIV/HCV coinfected patients with advanced liver disease |
| 264 | 1 | |c 2011 | |
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| 500 | |a Date Completed 26.01.2012 | ||
| 500 | |a Date Revised 21.11.2013 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a PURPOSE: There are few data about the safety and pharmacokinetics of lopinavir in HIV/HCV coinfected patients with very advanced liver disease | ||
| 520 | |a METHOD: Prospective study of 60 HIV/HCV coinfected patients who underwent a liver biopsy and received a lopinavir-based regimen. The rate of hepatotoxiciy and plasma trough levels were determined in absence/presence of cirrhosis (25 cases), especially in 11 patients with Child-Pugh stage B-C | ||
| 520 | |a RESULTS: Overall, geometric mean level of lopi-navir was 7,109 ng/mL (interquartile range [IQR], 5,163-9,029), without differences according to cirrhosis (7,662; IQR, 5,165-10,442) or not (6,708; IQR, 5,524-8,526; P = .6). In 11 patients with Child-Pugh stage B-C, trough level was 9,640 ng/mL (IQR, 1,620-11,622 ng/mL), but there was a 99% interpatient variability (72 to 13,331 ng/mL). During a follow-up of 195.2 patient-years, there were 7 cases of hepatotox-icity, with an incidence of 3.39 episodes/100 patient-years (2.2 to 7.9). This incidence was higher in patients with Child-Pugh stage B-C (5.43 episodes/100 patient-years). There were no differences in lopinavir trough levels between patients with or without liver toxicity (7,100 vs 7,119 ng/mL; P = .9) | ||
| 520 | |a CONCLUSION: The risk of lopinavir-associated hepatotoxicity in patients with very advanced liver disease is low. However, lopinavir plasma trough levels are increased, and there is a high interpatient variability | ||
| 650 | 4 | |a Clinical Trial | |
| 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 HIV Protease Inhibitors |2 NLM | |
| 650 | 7 | |a Lopinavir |2 NLM | |
| 650 | 7 | |a 2494G1JF75 |2 NLM | |
| 700 | 1 | |a Del Palacio, María |e verfasserin |4 aut | |
| 700 | 1 | |a Moya, Javier |e verfasserin |4 aut | |
| 700 | 1 | |a Rodriguez, José M |e verfasserin |4 aut | |
| 700 | 1 | |a Moreno, Ana |e verfasserin |4 aut | |
| 700 | 1 | |a Perez-Elías, María J |e verfasserin |4 aut | |
| 700 | 1 | |a Belso, Ana |e verfasserin |4 aut | |
| 700 | 1 | |a Dronda, Fernando |e verfasserin |4 aut | |
| 700 | 1 | |a Moreno, Santiago |e verfasserin |4 aut | |
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