Development of a multiroute physiologically based pharmacokinetic model for orbifloxacin in rabbits
| Autor: | F. Yang, W. Shi, H. Si, T. Kong, G. Wang, J. Zhang |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
Physiologically based pharmacokinetic modelling Tissue concentrations Administration Oral Absorption (skin) Pharmacology Kidney Injections Intramuscular Models Biological 0404 agricultural biotechnology Body compartment Pharmacokinetics Ciprofloxacin medicine Animals Muscle Skeletal General Veterinary Chemistry Myocardium 04 agricultural and veterinary sciences 040401 food science Anti-Bacterial Agents Liver Injections Intravenous Female Orbifloxacin Rabbits medicine.drug |
| Zdroj: | Journal of veterinary pharmacology and therapeutics. 41(4) |
| ISSN: | 1365-2885 |
| Popis: | To predict the orbifloxacin concentrations in rabbits after multiple routes of administration, a flow-limited multiroute physiologically based pharmacokinetic (PBPK) model was developed. Three routes of administration (IV, IM, and PO) were incorporated into this model. Physiological parameters including tissue weights and blood flows through different tissues were obtained from the literature. The tissue/plasma partition coefficients (PX s) for noneliminating tissues were calculated according to the area method, while the PX s for kidney and the rest of the body compartment, together with other parameters for absorption and elimination, were optimized based on the published concentrations. The comparisons between predicted and observed orbifloxacin concentrations proved its validity, and the present model predicted available concentration data well, including those in liver, kidney, muscle, lung, heart, and plasma after oral, intravenous, or intramuscular administration. A local sensitivity analysis was also performed, which showed that the parameters for oral absorption were most influential on the orbifloxacin concentrations. This model was used to predict plasma and tissue concentrations after multiple oral or intramuscular administration. This study demonstrated the feasibility of predicting drug residues in minor species after multiple routes of administration in the extra-label manner using the PBPK modeling. |
| Databáze: | OpenAIRE |
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