Inadequate Lopinavir Concentrations With Modified 8-Hourly Lopinavir/Ritonavir 4:1 Dosing During Rifampicin-based Tuberculosis Treatment in Children Living With HIV
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc..
BACKGROUND: Lopinavir/ritonavir plasma concentrations are profoundly reduced when co-administered with rifampicin. Super-boosting of lopinavir/ritonavir is limited by nonavailability of single-entity ritonavir, while double-dosing of co-formulated lopinavir/ritonavir given twice-daily produces suboptimal lopinavir concentrations in young children. We evaluated whether increased daily dosing with modified 8-hourly lopinavir/ritonavir 4:1 would maintain therapeutic plasma concentrations of lopinavir in children living with HIV receiving rifampicin-based antituberculosis treatment.
METHODS: Children with HIV/tuberculosis coinfection weighing 3.0 to 19.9 kg, on rifampicin-based antituberculosis treatment were commenced or switched to 8-hourly liquid lopinavir/ritonavir 4:1 with increased daily dosing using weight-band dosing approach. A standard twice-daily dosing of lopinavir/ritonavir was resumed 2 weeks after completing antituberculosis treatment. Plasma sampling was conducted during and 4 weeks after completing antituberculosis treatment.
RESULTS: Of 20 children enrolled; 15, 1-7 years old, had pharmacokinetics sampling available for analysis. Lopinavir concentrations (median [range]) on 8-hourly lopinavir/ritonavir co-administered with rifampicin (n = 15; area under the curve 0-24 55.32 mg/h/L [0.30-398.7 mg/h/L]; C max 3.04 mg/L [0.03-18.6 mg/L]; C 8hr 0.90 mg/L [0.01-13.7 mg/L]) were lower than on standard dosing without rifampicin (n = 12; area under the curve 24 121.63 mg/h/L [2.56-487.3 mg/h/L]; C max 9.45 mg/L [0.39-26.4 mg/L]; C 12hr 3.03 mg/L [0.01-17.7 mg/L]). During and after rifampicin cotreatment, only 7 of 15 (44.7%) and 8 of 12 (66.7%) children, respectively, achieved targeted pre-dose lopinavir concentrations ≥1mg/L.
CONCLUSIONS: Modified 8-hourly dosing of lopinavir/ritonavir failed to achieve adequate lopinavir concentrations with concurrent antituberculosis treatment. The subtherapeutic lopinavir exposures on standard dosing after antituberculosis treatment are of concern and requires further evaluation.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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Enthalten in: |
The Pediatric infectious disease journal - 42(2023), 10 vom: 01. Okt., Seite 899-904 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Chabala, Chishala [VerfasserIn] |
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Links: |
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Themen: |
2494G1JF75 |
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Anmerkungen: |
Date Completed 22.09.2023 Date Revised 13.03.2024 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1097/INF.0000000000004047 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM360061877 |
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245 | 1 | 0 | |a Inadequate Lopinavir Concentrations With Modified 8-Hourly Lopinavir/Ritonavir 4:1 Dosing During Rifampicin-based Tuberculosis Treatment in Children Living With HIV |
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500 | |a Date Revised 13.03.2024 | ||
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500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. | ||
520 | |a BACKGROUND: Lopinavir/ritonavir plasma concentrations are profoundly reduced when co-administered with rifampicin. Super-boosting of lopinavir/ritonavir is limited by nonavailability of single-entity ritonavir, while double-dosing of co-formulated lopinavir/ritonavir given twice-daily produces suboptimal lopinavir concentrations in young children. We evaluated whether increased daily dosing with modified 8-hourly lopinavir/ritonavir 4:1 would maintain therapeutic plasma concentrations of lopinavir in children living with HIV receiving rifampicin-based antituberculosis treatment | ||
520 | |a METHODS: Children with HIV/tuberculosis coinfection weighing 3.0 to 19.9 kg, on rifampicin-based antituberculosis treatment were commenced or switched to 8-hourly liquid lopinavir/ritonavir 4:1 with increased daily dosing using weight-band dosing approach. A standard twice-daily dosing of lopinavir/ritonavir was resumed 2 weeks after completing antituberculosis treatment. Plasma sampling was conducted during and 4 weeks after completing antituberculosis treatment | ||
520 | |a RESULTS: Of 20 children enrolled; 15, 1-7 years old, had pharmacokinetics sampling available for analysis. Lopinavir concentrations (median [range]) on 8-hourly lopinavir/ritonavir co-administered with rifampicin (n = 15; area under the curve 0-24 55.32 mg/h/L [0.30-398.7 mg/h/L]; C max 3.04 mg/L [0.03-18.6 mg/L]; C 8hr 0.90 mg/L [0.01-13.7 mg/L]) were lower than on standard dosing without rifampicin (n = 12; area under the curve 24 121.63 mg/h/L [2.56-487.3 mg/h/L]; C max 9.45 mg/L [0.39-26.4 mg/L]; C 12hr 3.03 mg/L [0.01-17.7 mg/L]). During and after rifampicin cotreatment, only 7 of 15 (44.7%) and 8 of 12 (66.7%) children, respectively, achieved targeted pre-dose lopinavir concentrations ≥1mg/L | ||
520 | |a CONCLUSIONS: Modified 8-hourly dosing of lopinavir/ritonavir failed to achieve adequate lopinavir concentrations with concurrent antituberculosis treatment. The subtherapeutic lopinavir exposures on standard dosing after antituberculosis treatment are of concern and requires further evaluation | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 7 | |a Rifampin |2 NLM | |
650 | 7 | |a VJT6J7R4TR |2 NLM | |
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650 | 7 | |a Ritonavir |2 NLM | |
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650 | 7 | |a Anti-HIV Agents |2 NLM | |
650 | 7 | |a Antitubercular Agents |2 NLM | |
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700 | 1 | |a Zimba, Kevin |e verfasserin |4 aut | |
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700 | 1 | |a Choo, Louise |e verfasserin |4 aut | |
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700 | 1 | |a Lungu, Joyce |e verfasserin |4 aut | |
700 | 1 | |a Mulenga, Veronica |e verfasserin |4 aut | |
700 | 1 | |a Crook, Angela |e verfasserin |4 aut | |
700 | 1 | |a Gibb, Diana |e verfasserin |4 aut | |
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700 | 1 | |a Wills, Genevieve |e investigator |4 oth | |
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700 | 1 | |a Teera, Jaqueline |e investigator |4 oth | |
700 | 1 | |a Owen-Powell, Ellen |e investigator |4 oth | |
700 | 1 | |a LeBeau, Kristen |e investigator |4 oth | |
700 | 1 | |a Baptiste, David |e investigator |4 oth | |
700 | 1 | |a McGowan, Charlotte |e investigator |4 oth | |
700 | 1 | |a Spyer, Moira |e investigator |4 oth | |
700 | 1 | |a Chabala, Chishala |e investigator |4 oth | |
700 | 1 | |a Mulenga, Veronica |e investigator |4 oth | |
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700 | 1 | |a Kapasa, Monica |e investigator |4 oth | |
700 | 1 | |a Zimba, Kevin |e investigator |4 oth | |
700 | 1 | |a Zyambo, Khozya |e investigator |4 oth | |
700 | 1 | |a Chungu, Chalilwe |e investigator |4 oth | |
700 | 1 | |a Tembo, Chimuka |e investigator |4 oth | |
700 | 1 | |a Kunda, Sharon |e investigator |4 oth | |
700 | 1 | |a Shingalili, Ellen |e investigator |4 oth | |
700 | 1 | |a Zulu, Semy |e investigator |4 oth | |
700 | 1 | |a Chipoya, Terence |e investigator |4 oth | |
700 | 1 | |a Mwanakalanga, Habulembe |e investigator |4 oth | |
700 | 1 | |a Chambela, Elias |e investigator |4 oth | |
700 | 1 | |a Hankombo, Jessy M |e investigator |4 oth | |
700 | 1 | |a Kalumbi, Mox Malama |e investigator |4 oth | |
700 | 1 | |a Chola, Daniel |e investigator |4 oth | |
700 | 1 | |a Malama, Stephen |e investigator |4 oth | |
700 | 1 | |a Wobudeya, Eric |e investigator |4 oth | |
700 | 1 | |a Musoke, Philippa |e investigator |4 oth | |
700 | 1 | |a Baldwin, Mboizi Robert |e investigator |4 oth | |
700 | 1 | |a Nansamba, Winnie |e investigator |4 oth | |
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700 | 1 | |a Ssengooba, Willy |e investigator |4 oth | |
700 | 1 | |a Businge, Gerald |e investigator |4 oth | |
700 | 1 | |a Hesseling, Anneke C |e investigator |4 oth | |
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