Pharmacokinetic and Pharmacodynamic Modeling of Enrofloxacin and Its Metabolite Ciprofloxacin in Pregnant Goats
The pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin, as well as the placental transfer of enrofloxacin and ciprofloxacin, have not been studied. The aims of this study were (1) to evaluate the pharmacokinetics of enrofloxacin and ciprofloxacin by intravenous and intramuscular admin...
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2025-06-01
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| author | Luis Adrian Ambros Verónica Kreil José Julio de Lucas Burneo Mariano Guillermo Tinti Manuel Ignacio San Andrés Larrea Augusto Matías Lorenzutti |
| author_facet | Luis Adrian Ambros Verónica Kreil José Julio de Lucas Burneo Mariano Guillermo Tinti Manuel Ignacio San Andrés Larrea Augusto Matías Lorenzutti |
| author_sort | Luis Adrian Ambros |
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| description | The pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin, as well as the placental transfer of enrofloxacin and ciprofloxacin, have not been studied. The aims of this study were (1) to evaluate the pharmacokinetics of enrofloxacin and ciprofloxacin by intravenous and intramuscular administration of 7.5 mg/kg in pregnant goats; (2) to determine the placental transfer of enrofloxacin and ciprofloxacin; (3) to conduct a PK/PD analysis to calculate the PK/PD cutoff of different dose regimens; and (4) to evaluate the tentative epidemiological cutoff values for coagulase-negative staphylococci wild-type isolates from goats. Plasmatic concentrations of enrofloxacin and ciprofloxacin in pregnant goats were well described by the parent–metabolite model. Simultaneous modeling of enrofloxacin and ciprofloxacin in each individual allowed for a PK/PD analysis that considered both drugs with antimicrobial activity. Our results show that both enrofloxacin and ciprofloxacin crossed the placenta in goats: fetal/maternal concentration ratio were 0.58 ± 0.05 and 0.03 ± 0.01 for enrofloxacin and ciprofloxacin. MIC values of coagulase-negative staphylococci isolates (<i>n</i> = 90) were obtained, and tentative epidemiological cutoffs were calculated at 0.25 and 0.5 mg/L for enrofloxacin and ciprofloxacin. According to PK/PDco values, an intravenous dose regimen of 10 mg/kg/day was considered the most appropriate, but based on the PK/PDco, culture, and AST data, an effective dosing regimen with the lowest possible dose could be selected to minimize the potential risk of fetal exposure to enrofloxacin. |
| format | Article |
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| institution | Kabale University |
| issn | 2306-7381 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| series | Veterinary Sciences |
| spelling | doaj-art-cb425751b5d74f9d933d7fc4a03c996f2025-08-20T03:32:32ZengMDPI AGVeterinary Sciences2306-73812025-06-0112658810.3390/vetsci12060588Pharmacokinetic and Pharmacodynamic Modeling of Enrofloxacin and Its Metabolite Ciprofloxacin in Pregnant GoatsLuis Adrian Ambros0Verónica Kreil1José Julio de Lucas Burneo2Mariano Guillermo Tinti3Manuel Ignacio San Andrés Larrea4Augusto Matías Lorenzutti5Cátedra de Farmacología, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Buenos Aires C.P. 1427, ArgentinaCátedra de Farmacología, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Buenos Aires C.P. 1427, ArgentinaDepartamento de Farmacología y Toxicología, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, SpainFacultad de Ciencias Agropecuarias, IRNASUS CONICET-Universidad Católica de Córdoba, Córdoba X5016DHK, ArgentinaDepartamento de Farmacología y Toxicología, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, SpainFacultad de Ciencias Agropecuarias, IRNASUS CONICET-Universidad Católica de Córdoba, Córdoba X5016DHK, ArgentinaThe pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin, as well as the placental transfer of enrofloxacin and ciprofloxacin, have not been studied. The aims of this study were (1) to evaluate the pharmacokinetics of enrofloxacin and ciprofloxacin by intravenous and intramuscular administration of 7.5 mg/kg in pregnant goats; (2) to determine the placental transfer of enrofloxacin and ciprofloxacin; (3) to conduct a PK/PD analysis to calculate the PK/PD cutoff of different dose regimens; and (4) to evaluate the tentative epidemiological cutoff values for coagulase-negative staphylococci wild-type isolates from goats. Plasmatic concentrations of enrofloxacin and ciprofloxacin in pregnant goats were well described by the parent–metabolite model. Simultaneous modeling of enrofloxacin and ciprofloxacin in each individual allowed for a PK/PD analysis that considered both drugs with antimicrobial activity. Our results show that both enrofloxacin and ciprofloxacin crossed the placenta in goats: fetal/maternal concentration ratio were 0.58 ± 0.05 and 0.03 ± 0.01 for enrofloxacin and ciprofloxacin. MIC values of coagulase-negative staphylococci isolates (<i>n</i> = 90) were obtained, and tentative epidemiological cutoffs were calculated at 0.25 and 0.5 mg/L for enrofloxacin and ciprofloxacin. According to PK/PDco values, an intravenous dose regimen of 10 mg/kg/day was considered the most appropriate, but based on the PK/PDco, culture, and AST data, an effective dosing regimen with the lowest possible dose could be selected to minimize the potential risk of fetal exposure to enrofloxacin.https://www.mdpi.com/2306-7381/12/6/588enrofloxacinciprofloxacingoatsgestationPK/PD modeling |
| spellingShingle | Luis Adrian Ambros Verónica Kreil José Julio de Lucas Burneo Mariano Guillermo Tinti Manuel Ignacio San Andrés Larrea Augusto Matías Lorenzutti Pharmacokinetic and Pharmacodynamic Modeling of Enrofloxacin and Its Metabolite Ciprofloxacin in Pregnant Goats Veterinary Sciences enrofloxacin ciprofloxacin goats gestation PK/PD modeling |
| title | Pharmacokinetic and Pharmacodynamic Modeling of Enrofloxacin and Its Metabolite Ciprofloxacin in Pregnant Goats |
| title_full | Pharmacokinetic and Pharmacodynamic Modeling of Enrofloxacin and Its Metabolite Ciprofloxacin in Pregnant Goats |
| title_fullStr | Pharmacokinetic and Pharmacodynamic Modeling of Enrofloxacin and Its Metabolite Ciprofloxacin in Pregnant Goats |
| title_full_unstemmed | Pharmacokinetic and Pharmacodynamic Modeling of Enrofloxacin and Its Metabolite Ciprofloxacin in Pregnant Goats |
| title_short | Pharmacokinetic and Pharmacodynamic Modeling of Enrofloxacin and Its Metabolite Ciprofloxacin in Pregnant Goats |
| title_sort | pharmacokinetic and pharmacodynamic modeling of enrofloxacin and its metabolite ciprofloxacin in pregnant goats |
| topic | enrofloxacin ciprofloxacin goats gestation PK/PD modeling |
| url | https://www.mdpi.com/2306-7381/12/6/588 |
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