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- Title
Population pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in chicken based on retrospective data, incorporating first-pass metabolism.
- Authors
QIAN-JI GUO; LING-LI HUANG; KE FANG; YU-LIAN WANG; DONG-MEI CHEN; YAN-FEI TAO; MENG-HONG DAI; ZHEN-LI LIU; DA-PENG PENG; ZONG-HUI YUAN
- Abstract
Guo, Q.-J., Huang, L.-L., Fang, K., Wang, Y.-L., Chen, D.-M., Tao, Y.-F., Dai, M.-H., Liu, Z.-L., Peng, D.-P., Yuan, Z.-H. Population pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in chicken based on retrospective data, incorporating first-pass metabolism. J. vet. Pharmacol. Therap. 33, 84–94. A population pharmacokinetic (PPK) model for enrofloxacin and its metabolite ciprofloxacin in chicken based on retrospective data was developed. Plasma concentrations of enrofloxacin and its metabolite ciprofloxacin were determined in blood samples from chicken administered either enrofloxacin via oral and intravenous routes or ciprofloxacin via intravenous injection. The disposition of enrofloxacin and ciprofloxacin was described simultaneously by an integrated mathematic model. Two compartments were used to describe the enrofloxacin and ciprofloxacin disposition profiles. The formation of ciprofloxacin was through the central compartment of enrofloxacin. The integrated model was estimated with nonlinear mixed effects model (NONMEM). The total clearance of enrofloxacin (CLEN) and ciprofloxacin (CLCP) was 0.613 L/h and 1.15 L/h, respectively. Correlation between CLEN, the central compartment volume of distribution for enrofloxacin (V2) and CLCP was estimated. After intravenous administration of enrofloxacin, the transformation rate of enrofloxacin to ciprofloxacin was 0.429 L/h. The bioavailability factor after oral administration was 0.926, and 12.6% of enrofloxacin after oral administration was transformed to ciprofloxacin via first-pass effect. Pharmacodynamic (PD) evaluation was performed using area under concentration time curve of active moiety from 0 to 24 h and MIC collected from literature. This study is the first one to use PPK method to investigate parent drug and its metabolite disposition and PDs using an integrated model in veterinary medicine.
- Subjects
FLUOROQUINOLONES; PHARMACOKINETICS; METABOLITES; METABOLISM; CIPROFLOXACIN; DRUG efficacy
- Publication
Journal of Veterinary Pharmacology & Therapeutics, 2010, Vol 33, Issue 1, p84
- ISSN
0140-7783
- Publication type
Article
- DOI
10.1111/j.1365-2885.2009.01106.x