Optimization and Validation of Dosage Regimen for Ceftiofur against <i>Pasteurella multocida</i> in Swine by Physiological Based Pharmacokinetic–Pharmacodynamic Model
Model informed drug development is a valuable tool for drug development and clinical application due to its ability to integrate variability and uncertainty of data. This study aimed to determine an optimal dosage of ceftiofur against <i>P. multocida</i> by ex vivo pharmacokinetic/pharma...
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| Format: | Article |
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MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/7/3722 |
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| author | Kun Mi Shanju Pu Yixuan Hou Lei Sun Kaixiang Zhou Wenjin Ma Xiangyue Xu Meixia Huo Zhenli Liu Changqing Xie Wei Qu Lingli Huang |
| author_facet | Kun Mi Shanju Pu Yixuan Hou Lei Sun Kaixiang Zhou Wenjin Ma Xiangyue Xu Meixia Huo Zhenli Liu Changqing Xie Wei Qu Lingli Huang |
| author_sort | Kun Mi |
| collection | DOAJ |
| description | Model informed drug development is a valuable tool for drug development and clinical application due to its ability to integrate variability and uncertainty of data. This study aimed to determine an optimal dosage of ceftiofur against <i>P. multocida</i> by ex vivo pharmacokinetic/pharmacodynamic (PK/PD) model and validate the dosage regimens by Physiological based Pharmacokinetic-Pharmacodynamic (PBPK/PD) model. The pharmacokinetic profiles of ceftiofur both in plasma and bronchoalveolar lavage fluid (BALF) are determined. PD performance of ceftiofur against <i>P. multocida</i> was investigated. By establishing PK/PD model, PK/PD parameters and doses were determined. PBPK model and PBPK/PD model were developed to validate the dosage efficacy. The PK/PD parameters, AUC<sub>0–24 h</sub>/MIC, for bacteriostatic action, bactericidal action and elimination were determined as 44.02, 89.40, and 119.90 h and the corresponding dosages were determined as 0.22, 0.46, and 0.64 mg/kg, respectively. AUC<sub>24 h</sub>/MIC and AUC <sub>72 h</sub>/MIC are simulated by PBPK model, compared with the PK/PD parameters, the therapeutic effect can reach probability of target attainment (PTA) of 90%. The time-courses of bacterial growth were predicted by the PBPK/PD model, which indicated the dosage of 0.46 mg/kg body weight could inhibit the bacterial growth and perform good bactericidal effect. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T11:47:02Z |
| publishDate | 2022-03-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fb78cf076e9f4e5eb17e0954fa3d80432023-11-30T23:21:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01237372210.3390/ijms23073722Optimization and Validation of Dosage Regimen for Ceftiofur against <i>Pasteurella multocida</i> in Swine by Physiological Based Pharmacokinetic–Pharmacodynamic ModelKun Mi0Shanju Pu1Yixuan Hou2Lei Sun3Kaixiang Zhou4Wenjin Ma5Xiangyue Xu6Meixia Huo7Zhenli Liu8Changqing Xie9Wei Qu10Lingli Huang11National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, ChinaMAO Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, ChinaMAO Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, ChinaMAO Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, ChinaModel informed drug development is a valuable tool for drug development and clinical application due to its ability to integrate variability and uncertainty of data. This study aimed to determine an optimal dosage of ceftiofur against <i>P. multocida</i> by ex vivo pharmacokinetic/pharmacodynamic (PK/PD) model and validate the dosage regimens by Physiological based Pharmacokinetic-Pharmacodynamic (PBPK/PD) model. The pharmacokinetic profiles of ceftiofur both in plasma and bronchoalveolar lavage fluid (BALF) are determined. PD performance of ceftiofur against <i>P. multocida</i> was investigated. By establishing PK/PD model, PK/PD parameters and doses were determined. PBPK model and PBPK/PD model were developed to validate the dosage efficacy. The PK/PD parameters, AUC<sub>0–24 h</sub>/MIC, for bacteriostatic action, bactericidal action and elimination were determined as 44.02, 89.40, and 119.90 h and the corresponding dosages were determined as 0.22, 0.46, and 0.64 mg/kg, respectively. AUC<sub>24 h</sub>/MIC and AUC <sub>72 h</sub>/MIC are simulated by PBPK model, compared with the PK/PD parameters, the therapeutic effect can reach probability of target attainment (PTA) of 90%. The time-courses of bacterial growth were predicted by the PBPK/PD model, which indicated the dosage of 0.46 mg/kg body weight could inhibit the bacterial growth and perform good bactericidal effect.https://www.mdpi.com/1422-0067/23/7/3722ceftiofur<i>Pasteurella multocida</i>PBPK/PD modeldosage regimenmathematical model |
| spellingShingle | Kun Mi Shanju Pu Yixuan Hou Lei Sun Kaixiang Zhou Wenjin Ma Xiangyue Xu Meixia Huo Zhenli Liu Changqing Xie Wei Qu Lingli Huang Optimization and Validation of Dosage Regimen for Ceftiofur against <i>Pasteurella multocida</i> in Swine by Physiological Based Pharmacokinetic–Pharmacodynamic Model International Journal of Molecular Sciences ceftiofur <i>Pasteurella multocida</i> PBPK/PD model dosage regimen mathematical model |
| title | Optimization and Validation of Dosage Regimen for Ceftiofur against <i>Pasteurella multocida</i> in Swine by Physiological Based Pharmacokinetic–Pharmacodynamic Model |
| title_full | Optimization and Validation of Dosage Regimen for Ceftiofur against <i>Pasteurella multocida</i> in Swine by Physiological Based Pharmacokinetic–Pharmacodynamic Model |
| title_fullStr | Optimization and Validation of Dosage Regimen for Ceftiofur against <i>Pasteurella multocida</i> in Swine by Physiological Based Pharmacokinetic–Pharmacodynamic Model |
| title_full_unstemmed | Optimization and Validation of Dosage Regimen for Ceftiofur against <i>Pasteurella multocida</i> in Swine by Physiological Based Pharmacokinetic–Pharmacodynamic Model |
| title_short | Optimization and Validation of Dosage Regimen for Ceftiofur against <i>Pasteurella multocida</i> in Swine by Physiological Based Pharmacokinetic–Pharmacodynamic Model |
| title_sort | optimization and validation of dosage regimen for ceftiofur against i pasteurella multocida i in swine by physiological based pharmacokinetic pharmacodynamic model |
| topic | ceftiofur <i>Pasteurella multocida</i> PBPK/PD model dosage regimen mathematical model |
| url | https://www.mdpi.com/1422-0067/23/7/3722 |
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