Dose optimization with population pharmacokinetics of ritonavir-boosted lopinavir for Thai people living with HIV with and without active tuberculosis
Copyright © 2022 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved..
BACKGROUND: Prior to dolutegravir availability, ritonavir-boosted lopinavir (LPV/r) was an alternative recommendation when first-line drugs could not be used. A high concentration of protease inhibitors was observed in the Thai people living with HIV (PLWH). Thus, dose reduction of LPV/r may be possible. However, the pharmacokinetics and dose optimization of LPV/r have never been investigated. This study aimed to develop a population pharmacokinetic model of LPV/r and provide dosage optimization in Thai PLWH.
METHODS: LPV and RTV trough concentrations from Thai PLWH were combined with intensive data. The data were analyzed by the nonlinear mixed-effects modeling approach. The influence of RTV concentration on LPV oral clearance (CL/F) was investigated.
RESULTS: Rifampicin (RIF) use increased LPV and RTV CL/F by 2.16-fold and 1.99-fold, respectively. The reduced dose of 300/75 and 200/150 mg twice daily provided a comparable percentage of patients achieving LPV target trough concentration to the standard dose for PI-naïve patients. For HIV/TB co-infected patients receiving RIF who could not tolerate the recommended dose, the reduced dose of 600/150 mg twice daily was recommended.
CONCLUSION: The population pharmacokinetic model was developed by integrating the interaction between LPV and RTV. The reduced LPV/r dosage offers sufficient LPV exposure for Thai PLWH.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:47 |
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| Enthalten in: |
Drug metabolism and pharmacokinetics - 47(2022) vom: 06. Dez., Seite 100478 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chaivichacharn, Piyawat [VerfasserIn] |
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| Links: |
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| Themen: |
2494G1JF75 |
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| Anmerkungen: |
Date Completed 05.12.2022 Date Revised 05.12.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.dmpk.2022.100478 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM348886969 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved. | ||
| 520 | |a BACKGROUND: Prior to dolutegravir availability, ritonavir-boosted lopinavir (LPV/r) was an alternative recommendation when first-line drugs could not be used. A high concentration of protease inhibitors was observed in the Thai people living with HIV (PLWH). Thus, dose reduction of LPV/r may be possible. However, the pharmacokinetics and dose optimization of LPV/r have never been investigated. This study aimed to develop a population pharmacokinetic model of LPV/r and provide dosage optimization in Thai PLWH | ||
| 520 | |a METHODS: LPV and RTV trough concentrations from Thai PLWH were combined with intensive data. The data were analyzed by the nonlinear mixed-effects modeling approach. The influence of RTV concentration on LPV oral clearance (CL/F) was investigated | ||
| 520 | |a RESULTS: Rifampicin (RIF) use increased LPV and RTV CL/F by 2.16-fold and 1.99-fold, respectively. The reduced dose of 300/75 and 200/150 mg twice daily provided a comparable percentage of patients achieving LPV target trough concentration to the standard dose for PI-naïve patients. For HIV/TB co-infected patients receiving RIF who could not tolerate the recommended dose, the reduced dose of 600/150 mg twice daily was recommended | ||
| 520 | |a CONCLUSION: The population pharmacokinetic model was developed by integrating the interaction between LPV and RTV. The reduced LPV/r dosage offers sufficient LPV exposure for Thai PLWH | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Lopinavir | |
| 650 | 4 | |a NONMEM | |
| 650 | 4 | |a Population pharmacokinetics | |
| 650 | 4 | |a Ritonavir | |
| 650 | 4 | |a Thai people living with HIV | |
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| 650 | 7 | |a HIV Protease Inhibitors |2 NLM | |
| 650 | 7 | |a Anti-HIV Agents |2 NLM | |
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| 700 | 1 | |a Gatechompol, Sivaporn |e verfasserin |4 aut | |
| 700 | 1 | |a Ubolyam, Sasiwimol |e verfasserin |4 aut | |
| 700 | 1 | |a Punyawudho, Baralee |e verfasserin |4 aut | |
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