Population pharmacokinetics of voriconazole and initial dosage optimization in patients with talaromycosis
The high variability and unpredictability of the plasma concentration of voriconazole (VRC) pose a major challenge for clinical administration. The aim of this study was to develop a population pharmacokinetics (PPK) model of VRC and identify the factors influencing VRC PPK in patients with talaromy...
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.982981/full |
| _version_ | 1798001224002306048 |
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| author | Zhiwen Jiang Zhiwen Jiang Yinyi Wei Weie Huang Bingkun Li Bingkun Li Siru Zhou Liuwei Liao Liuwei Liao Tiantian Li Tianwei Liang Tianwei Liang Xiaoshu Yu Xiuying Li Xiuying Li Changjing Zhou Cunwei Cao Cunwei Cao TaoTao Liu |
| author_facet | Zhiwen Jiang Zhiwen Jiang Yinyi Wei Weie Huang Bingkun Li Bingkun Li Siru Zhou Liuwei Liao Liuwei Liao Tiantian Li Tianwei Liang Tianwei Liang Xiaoshu Yu Xiuying Li Xiuying Li Changjing Zhou Cunwei Cao Cunwei Cao TaoTao Liu |
| author_sort | Zhiwen Jiang |
| collection | DOAJ |
| description | The high variability and unpredictability of the plasma concentration of voriconazole (VRC) pose a major challenge for clinical administration. The aim of this study was to develop a population pharmacokinetics (PPK) model of VRC and identify the factors influencing VRC PPK in patients with talaromycosis. Medical records and VRC medication history of patients with talaromycosis who were treated with VRC as initial therapy were collected. A total of 233 blood samples from 69 patients were included in the study. A PPK model was developed using the nonlinear mixed-effects models (NONMEM). Monte Carlo simulation was applied to optimize the initial dosage regimens with a therapeutic range of 1.0–5.5 mg/L as the target plasma trough concentration. A one-compartment model with first-order absorption and elimination adequately described the data. The typical voriconazole clearance was 4.34 L/h, the volume of distribution was 97.4 L, the absorption rate constant was set at 1.1 h-1, and the bioavailability was 95.1%. Clearance was found to be significantly associated with C-reactive protein (CRP). CYP2C19 polymorphisms had no effect on voriconazole pharmacokinetic parameters. Monte Carlo simulation based on CRP levels showed that a loading dose of 250 mg/12 h and a maintenance dose of 100 mg/12 h are recommended for patients with CRP ≤ 96 mg/L, whereas a loading dose of 200 mg/12 h and a maintenance dose of 75 mg/12 h are recommended for patients with CRP > 96 mg/L. The average probability of target attainment of the optimal dosage regimen in CRP ≤ 96 mg/L and CRP > 96 mg/L groups were 61.3% and 13.6% higher than with empirical medication, and the proportion of Cmin > 5.5 mg/L decreased by 28.9%. In conclusion, the VRC PPK model for talaromycosis patients shows good robustness and predictive performance, which can provide a reference for the clinical individualization of VRC. Adjusting initial dosage regimens based on CRP may promote the rational use of VRC. |
| first_indexed | 2024-04-11T11:32:49Z |
| format | Article |
| id | doaj.art-b2824caf895a4c7ea93a8b308ff3dcd0 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T11:32:49Z |
| publishDate | 2022-09-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-b2824caf895a4c7ea93a8b308ff3dcd02022-12-22T04:26:04ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-09-011310.3389/fphar.2022.982981982981Population pharmacokinetics of voriconazole and initial dosage optimization in patients with talaromycosisZhiwen Jiang0Zhiwen Jiang1Yinyi Wei2Weie Huang3Bingkun Li4Bingkun Li5Siru Zhou6Liuwei Liao7Liuwei Liao8Tiantian Li9Tianwei Liang10Tianwei Liang11Xiaoshu Yu12Xiuying Li13Xiuying Li14Changjing Zhou15Cunwei Cao16Cunwei Cao17TaoTao Liu18Department of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Health Commission Key Lab of Fungi and Mycosis Research and Prevention, Nanning, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Infectious Diseases, Baise People’s Hospital, Baise, ChinaDepartment of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Health Commission Key Lab of Fungi and Mycosis Research and Prevention, Nanning, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Health Commission Key Lab of Fungi and Mycosis Research and Prevention, Nanning, ChinaGuangxi Health Commission Key Lab of Fungi and Mycosis Research and Prevention, Nanning, ChinaDepartment of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Health Commission Key Lab of Fungi and Mycosis Research and Prevention, Nanning, ChinaDepartment of Infectious Diseases, Baise People’s Hospital, Baise, ChinaDepartment of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Health Commission Key Lab of Fungi and Mycosis Research and Prevention, Nanning, ChinaDepartment of Infectious Diseases, Baise People’s Hospital, Baise, ChinaDepartment of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Health Commission Key Lab of Fungi and Mycosis Research and Prevention, Nanning, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaThe high variability and unpredictability of the plasma concentration of voriconazole (VRC) pose a major challenge for clinical administration. The aim of this study was to develop a population pharmacokinetics (PPK) model of VRC and identify the factors influencing VRC PPK in patients with talaromycosis. Medical records and VRC medication history of patients with talaromycosis who were treated with VRC as initial therapy were collected. A total of 233 blood samples from 69 patients were included in the study. A PPK model was developed using the nonlinear mixed-effects models (NONMEM). Monte Carlo simulation was applied to optimize the initial dosage regimens with a therapeutic range of 1.0–5.5 mg/L as the target plasma trough concentration. A one-compartment model with first-order absorption and elimination adequately described the data. The typical voriconazole clearance was 4.34 L/h, the volume of distribution was 97.4 L, the absorption rate constant was set at 1.1 h-1, and the bioavailability was 95.1%. Clearance was found to be significantly associated with C-reactive protein (CRP). CYP2C19 polymorphisms had no effect on voriconazole pharmacokinetic parameters. Monte Carlo simulation based on CRP levels showed that a loading dose of 250 mg/12 h and a maintenance dose of 100 mg/12 h are recommended for patients with CRP ≤ 96 mg/L, whereas a loading dose of 200 mg/12 h and a maintenance dose of 75 mg/12 h are recommended for patients with CRP > 96 mg/L. The average probability of target attainment of the optimal dosage regimen in CRP ≤ 96 mg/L and CRP > 96 mg/L groups were 61.3% and 13.6% higher than with empirical medication, and the proportion of Cmin > 5.5 mg/L decreased by 28.9%. In conclusion, the VRC PPK model for talaromycosis patients shows good robustness and predictive performance, which can provide a reference for the clinical individualization of VRC. Adjusting initial dosage regimens based on CRP may promote the rational use of VRC.https://www.frontiersin.org/articles/10.3389/fphar.2022.982981/fullvoriconazoletalaromycosispopulation pharmacokineticsdosage optimizationMonte Carlo simulationC- reactive protein (CRP) |
| spellingShingle | Zhiwen Jiang Zhiwen Jiang Yinyi Wei Weie Huang Bingkun Li Bingkun Li Siru Zhou Liuwei Liao Liuwei Liao Tiantian Li Tianwei Liang Tianwei Liang Xiaoshu Yu Xiuying Li Xiuying Li Changjing Zhou Cunwei Cao Cunwei Cao TaoTao Liu Population pharmacokinetics of voriconazole and initial dosage optimization in patients with talaromycosis Frontiers in Pharmacology voriconazole talaromycosis population pharmacokinetics dosage optimization Monte Carlo simulation C- reactive protein (CRP) |
| title | Population pharmacokinetics of voriconazole and initial dosage optimization in patients with talaromycosis |
| title_full | Population pharmacokinetics of voriconazole and initial dosage optimization in patients with talaromycosis |
| title_fullStr | Population pharmacokinetics of voriconazole and initial dosage optimization in patients with talaromycosis |
| title_full_unstemmed | Population pharmacokinetics of voriconazole and initial dosage optimization in patients with talaromycosis |
| title_short | Population pharmacokinetics of voriconazole and initial dosage optimization in patients with talaromycosis |
| title_sort | population pharmacokinetics of voriconazole and initial dosage optimization in patients with talaromycosis |
| topic | voriconazole talaromycosis population pharmacokinetics dosage optimization Monte Carlo simulation C- reactive protein (CRP) |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.982981/full |
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