Population pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in chicken based on retrospective data, incorporating first-pass metabolism.
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.
Guo
Qian-Ji
QJ
National Reference Laboratory of Veterinary Drug Residues, Wuhan, China.
Huang
Ling-Li
LL
Fang
Ke
K
Wang
Yu-Lian
YL
Chen
Dong-Mei
DM
Tao
Yan-Fei
YF
Dai
Meng-Hong
MH
Liu
Zhen-Li
ZL
Peng
Da-Peng
DP
Yuan
Zong-Hui
ZH
D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001835:Body Weight; D002645:Chickens / Q000097:blood*; D002939:Ciprofloxacin / Q000097:blood / Q000493:pharmacokinetics*; D000077422:Enrofloxacin; D024841:Fluoroquinolones / Q000097:blood / Q000493:pharmacokinetics*; D008954:Models, Biological; D012189:Retrospective Studies
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D000077422:Enrofloxacin; D002939:Ciprofloxacin