Inadequate lopinavir concentrations with modified 8-hourly lopinavir/ritonavir 4:1 dosing during rifampicin-based tuberculosis treatment in children living with HIV. Chabala, C., Turkova, A., Kapasa, M., LeBeau, K., Tembo, C. H, Zimba, K., Weisner, L., Zyambo, K., Choo, L., Chungu, C., Lungu, J., Mulenga, V., Crook, A., Gibb, D., McIlleron, H., & trial Team, o. b. o. t. S. The Pediatric Infectious Disease Journal, 42(10):899–904, 2023.
Inadequate lopinavir concentrations with modified 8-hourly lopinavir/ritonavir 4:1 dosing during rifampicin-based tuberculosis treatment in children living with HIV [link]Paper  abstract   bibtex   
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 curve0–24 55.32 mg/h/L [0.30–398.7 mg/h/L]; Cmax 3.04 mg/L [0.03–18.6 mg/L]; C8hr 0.90 mg/L [0.01–13.7 mg/L]) were lower than on standard dosing without rifampicin (n = 12; area under the curve24 121.63 mg/h/L [2.56–487.3 mg/h/L]; Cmax 9.45 mg/L [0.39–26.4 mg/L]; C12hr 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.
@article{Chabala9900,
abstract = {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 curve0–24 55.32 mg/h/L [0.30–398.7 mg/h/L]; Cmax 3.04 mg/L [0.03–18.6 mg/L]; C8hr 0.90 mg/L [0.01–13.7 mg/L]) were lower than on standard dosing without rifampicin (n = 12; area under the curve24 121.63 mg/h/L [2.56–487.3 mg/h/L]; Cmax 9.45 mg/L [0.39–26.4 mg/L]; C12hr 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.},
author = {Chabala, Chishala and Turkova, Anna and Kapasa, Monica and LeBeau, Kristen and Tembo, Chimuka H and Zimba, Kevin and Weisner, Lubbe and Zyambo, Khozya and Choo, Louise and Chungu, Chalilwe and Lungu, Joyce and Mulenga, Veronica and Crook, Angela and Gibb, Diana and McIlleron, Helen and trial Team, on behalf of the SHINE},
issn = {0891-3668},
journal = {The Pediatric Infectious Disease Journal},
keywords = {HIV,OA,fund{\_}not{\_}ack,lopinavir/ritonavir,original,pharmacokinetics,rifampicin,tuberculosis},
mendeley-tags = {OA,fund{\_}not{\_}ack,original},
number = {10},
pages = {899--904},
pmid = {37506295},
title = {{Inadequate lopinavir concentrations with modified 8-hourly lopinavir/ritonavir 4:1 dosing during rifampicin-based tuberculosis treatment in children living with HIV}},
url = {https://journals.lww.com/pidj/Fulltext/9900/Inadequate{\_}Lopinavir{\_}Concentrations{\_}With{\_}Modified.528.aspx},
volume = {42},
year = {2023}
}
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