Pharmacokinetic/pharmacodynamic relationship of a novel pleuromutilin derivative p-furoylamphenmulin against Mycoplasma gallisepticum in vivo in chickens
Mycoplasma gallisepticum (M. gallisepticum, MG) is the primary pathogen of chronic respiratory disease (CRD) in chickens and leads to pneumonia and air sacculitis in infected chickens and a corresponding economic loss for the poultry industry. The pleuromutilins have excellent anti-mycoplasmal activ...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-08-01
|
| Series: | Poultry Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0032579125004912 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849303959987027968 |
|---|---|
| author | Xirui Xia Huifang Zhao Yaxi Li Xiangyang Long Xuezhen Liu Mingyang Bai Youzhi Tang Xiangguang Shen Huanzhong Ding |
| author_facet | Xirui Xia Huifang Zhao Yaxi Li Xiangyang Long Xuezhen Liu Mingyang Bai Youzhi Tang Xiangguang Shen Huanzhong Ding |
| author_sort | Xirui Xia |
| collection | DOAJ |
| description | Mycoplasma gallisepticum (M. gallisepticum, MG) is the primary pathogen of chronic respiratory disease (CRD) in chickens and leads to pneumonia and air sacculitis in infected chickens and a corresponding economic loss for the poultry industry. The pleuromutilins have excellent anti-mycoplasmal activity and we evaluated the in vivo activity of a new derivative 22-((4-((2-furan-1-yl)acetamido)phenyl)thio) deoxypleuromutilin (p-furoylamphenmulin) against M. gallisepticum. A plasma pharmacokinetic (PK) study and an in vivo pharmacodynamic (PD) study of p-furoylamphenmulin were performed using an M. gallisepticum-infected chicken model. Based on the PK/PD results, a preliminary recommended dose was calculated. The minimum inhibitory concentration (MIC) of p-furoylamphenmulin against M. gallisepticum was 0.001953125 μg/mL. PK results indicated that the absorption half-life (T1/2ka) in infected chicks was 0.10 h, elimination half-life (T1/2kel) was 4.23 h. The areas under the concentration-time curve at 24 h (AUC24h) for 5, 40, and 80 mg/kg single-dose injections were 1.49, 10.15, and 18.56 μg·h/mL, respectively. The peak concentrations (Cmax) of 5, 40, and 80 mg/kg were 0.56, 5.79, and 9.53 μg/mL, respectively. The PD results indicated that at doses of 70 and 80 mg/kg, the mycoplasmal counts in lungs decreased by 3.39 and 3.28 Log10CFU/mL, respectively, achieving a bactericidal effect. Through PK/PD fitting, the target values corresponding to reducing the lung mycoplasma load by 3 Log10 CFU/mL of AUC24h/MIC and Cmax/MIC were 8288.29 h and 4299.30, respectively, and the calculated dosage using formula (2) was 62.64 mg/kg, under the regimen of intramuscular injection once every 24 h for 3 consecutive days. In addition, the effect of high-dose p-furoylamphenmulin on the relief of air sac lesions was significant. These results provide a basis for developing and applying p-furoylamphenmulin and provide a preliminary medication regimen. |
| format | Article |
| id | doaj-art-840a6a1fbbaf44c1adcf5c755c14bd1d |
| institution | Kabale University |
| issn | 0032-5791 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Poultry Science |
| spelling | doaj-art-840a6a1fbbaf44c1adcf5c755c14bd1d2025-08-20T03:55:53ZengElsevierPoultry Science0032-57912025-08-01104810524910.1016/j.psj.2025.105249Pharmacokinetic/pharmacodynamic relationship of a novel pleuromutilin derivative p-furoylamphenmulin against Mycoplasma gallisepticum in vivo in chickensXirui Xia0Huifang Zhao1Yaxi Li2Xiangyang Long3Xuezhen Liu4Mingyang Bai5Youzhi Tang6Xiangguang Shen7Huanzhong Ding8Guangdong Key Laboratory for Veterinary Drug Development and Safety evaluation, College of Veterinary Medicine, South China Agricultural University, 510642 Guangzhou, ChinaGuangdong Key Laboratory for Veterinary Drug Development and Safety evaluation, College of Veterinary Medicine, South China Agricultural University, 510642 Guangzhou, ChinaGuangdong Key Laboratory for Veterinary Drug Development and Safety evaluation, College of Veterinary Medicine, South China Agricultural University, 510642 Guangzhou, ChinaGuangdong Key Laboratory for Veterinary Drug Development and Safety evaluation, College of Veterinary Medicine, South China Agricultural University, 510642 Guangzhou, ChinaGuangdong Key Laboratory for Veterinary Drug Development and Safety evaluation, College of Veterinary Medicine, South China Agricultural University, 510642 Guangzhou, ChinaGuangdong Key Laboratory for Veterinary Drug Development and Safety evaluation, College of Veterinary Medicine, South China Agricultural University, 510642 Guangzhou, ChinaGuangdong Key Laboratory for Veterinary Drug Development and Safety evaluation, College of Veterinary Medicine, South China Agricultural University, 510642 Guangzhou, ChinaGuangdong Key Laboratory for Veterinary Drug Development and Safety evaluation, College of Veterinary Medicine, South China Agricultural University, 510642 Guangzhou, ChinaCorresponding author.; Guangdong Key Laboratory for Veterinary Drug Development and Safety evaluation, College of Veterinary Medicine, South China Agricultural University, 510642 Guangzhou, ChinaMycoplasma gallisepticum (M. gallisepticum, MG) is the primary pathogen of chronic respiratory disease (CRD) in chickens and leads to pneumonia and air sacculitis in infected chickens and a corresponding economic loss for the poultry industry. The pleuromutilins have excellent anti-mycoplasmal activity and we evaluated the in vivo activity of a new derivative 22-((4-((2-furan-1-yl)acetamido)phenyl)thio) deoxypleuromutilin (p-furoylamphenmulin) against M. gallisepticum. A plasma pharmacokinetic (PK) study and an in vivo pharmacodynamic (PD) study of p-furoylamphenmulin were performed using an M. gallisepticum-infected chicken model. Based on the PK/PD results, a preliminary recommended dose was calculated. The minimum inhibitory concentration (MIC) of p-furoylamphenmulin against M. gallisepticum was 0.001953125 μg/mL. PK results indicated that the absorption half-life (T1/2ka) in infected chicks was 0.10 h, elimination half-life (T1/2kel) was 4.23 h. The areas under the concentration-time curve at 24 h (AUC24h) for 5, 40, and 80 mg/kg single-dose injections were 1.49, 10.15, and 18.56 μg·h/mL, respectively. The peak concentrations (Cmax) of 5, 40, and 80 mg/kg were 0.56, 5.79, and 9.53 μg/mL, respectively. The PD results indicated that at doses of 70 and 80 mg/kg, the mycoplasmal counts in lungs decreased by 3.39 and 3.28 Log10CFU/mL, respectively, achieving a bactericidal effect. Through PK/PD fitting, the target values corresponding to reducing the lung mycoplasma load by 3 Log10 CFU/mL of AUC24h/MIC and Cmax/MIC were 8288.29 h and 4299.30, respectively, and the calculated dosage using formula (2) was 62.64 mg/kg, under the regimen of intramuscular injection once every 24 h for 3 consecutive days. In addition, the effect of high-dose p-furoylamphenmulin on the relief of air sac lesions was significant. These results provide a basis for developing and applying p-furoylamphenmulin and provide a preliminary medication regimen.http://www.sciencedirect.com/science/article/pii/S0032579125004912Mycoplasma gallisepticump-furoylamphenmulinPleuromutilinPK/PDChicken |
| spellingShingle | Xirui Xia Huifang Zhao Yaxi Li Xiangyang Long Xuezhen Liu Mingyang Bai Youzhi Tang Xiangguang Shen Huanzhong Ding Pharmacokinetic/pharmacodynamic relationship of a novel pleuromutilin derivative p-furoylamphenmulin against Mycoplasma gallisepticum in vivo in chickens Poultry Science Mycoplasma gallisepticum p-furoylamphenmulin Pleuromutilin PK/PD Chicken |
| title | Pharmacokinetic/pharmacodynamic relationship of a novel pleuromutilin derivative p-furoylamphenmulin against Mycoplasma gallisepticum in vivo in chickens |
| title_full | Pharmacokinetic/pharmacodynamic relationship of a novel pleuromutilin derivative p-furoylamphenmulin against Mycoplasma gallisepticum in vivo in chickens |
| title_fullStr | Pharmacokinetic/pharmacodynamic relationship of a novel pleuromutilin derivative p-furoylamphenmulin against Mycoplasma gallisepticum in vivo in chickens |
| title_full_unstemmed | Pharmacokinetic/pharmacodynamic relationship of a novel pleuromutilin derivative p-furoylamphenmulin against Mycoplasma gallisepticum in vivo in chickens |
| title_short | Pharmacokinetic/pharmacodynamic relationship of a novel pleuromutilin derivative p-furoylamphenmulin against Mycoplasma gallisepticum in vivo in chickens |
| title_sort | pharmacokinetic pharmacodynamic relationship of a novel pleuromutilin derivative p furoylamphenmulin against mycoplasma gallisepticum in vivo in chickens |
| topic | Mycoplasma gallisepticum p-furoylamphenmulin Pleuromutilin PK/PD Chicken |
| url | http://www.sciencedirect.com/science/article/pii/S0032579125004912 |
| work_keys_str_mv | AT xiruixia pharmacokineticpharmacodynamicrelationshipofanovelpleuromutilinderivativepfuroylamphenmulinagainstmycoplasmagallisepticuminvivoinchickens AT huifangzhao pharmacokineticpharmacodynamicrelationshipofanovelpleuromutilinderivativepfuroylamphenmulinagainstmycoplasmagallisepticuminvivoinchickens AT yaxili pharmacokineticpharmacodynamicrelationshipofanovelpleuromutilinderivativepfuroylamphenmulinagainstmycoplasmagallisepticuminvivoinchickens AT xiangyanglong pharmacokineticpharmacodynamicrelationshipofanovelpleuromutilinderivativepfuroylamphenmulinagainstmycoplasmagallisepticuminvivoinchickens AT xuezhenliu pharmacokineticpharmacodynamicrelationshipofanovelpleuromutilinderivativepfuroylamphenmulinagainstmycoplasmagallisepticuminvivoinchickens AT mingyangbai pharmacokineticpharmacodynamicrelationshipofanovelpleuromutilinderivativepfuroylamphenmulinagainstmycoplasmagallisepticuminvivoinchickens AT youzhitang pharmacokineticpharmacodynamicrelationshipofanovelpleuromutilinderivativepfuroylamphenmulinagainstmycoplasmagallisepticuminvivoinchickens AT xiangguangshen pharmacokineticpharmacodynamicrelationshipofanovelpleuromutilinderivativepfuroylamphenmulinagainstmycoplasmagallisepticuminvivoinchickens AT huanzhongding pharmacokineticpharmacodynamicrelationshipofanovelpleuromutilinderivativepfuroylamphenmulinagainstmycoplasmagallisepticuminvivoinchickens |