랫드에게 도세탁셀 정맥투여 후 약물동태학적 모델링과 시뮬레이션 연구

Pharmacokinetic Modeling & Simulation of Docetaxel following Intravenous Administration to Rat

Docetaxel is an anti-mitotic chemotherapy agent that is approved for treatment of malignancies including breast, gastric, prostate and non-small cell lung cancer. The aim of the study was to investigate the pharmacokinetics of docetaxel after intravenous administration to rats using noncompartmental analysis and quantitative modeling approaches. Ten SD rats administered 5 mg/kg of Taxotere？？ intravenously and the plasma concentrations of docetaxel were measured by liquid chromatography- tandem mass spectrometry. The data were analyzed by modeling approaches using ADAPT5 and model discrimination was determined by the likelihood-ratio test. The concentration at time 0 was 398.7±71.9 ng/mL, and the area under the plasma concentration-versus-time curve from time zero to the last measurable concentration was 436.3 ±157.2 ng·h/ mL. The two-compartment model with first-order elimination was sufficient to explain the pharmacokinetic properties after single intravenous administration of docetaxel to rats. Simulation was achieved to predict the plasma concentration profiles of docetaxel for multiple dosing, several dose, formulation releasing rate and volume of distribution. This study provides pharmacokinetic information in rats that will aid future development of improved formulations for docetaxel.