酮洛芬β-CD包合物在兔体内药代动力学—药效动力学研究

STUDIES ON THE PHARMACOKINETIC PHARMACODYNAMIC MODEL OF KETOPROFEN β CD INCLUSION COMPLEX IN RABBITS

为了解药物经βＣＤ包合后的生物体内性质建立了ＨＰＬＣＵＶ法以测定酮洛芬在家兔体内的血药浓度。用酵母诱导家兔的发热反应，考察酮洛芬βＣＤ包合物与其单体的药代动力学—药效动力学（ＰＫＰＤ）。结果表明：建立的ＨＰＬＣＵＶ法简便可行；酮洛芬βＣＤ包合物在分布相Ｔ１／２α为０４ｈ，而其单体的Ｔ１／２α为０５６ｈ，反映了包合后酮洛芬吸收更快；在效应—浓度—时间曲线上，包合后的酮洛芬早期效应略高；酮洛芬给药后的效应峰值滞后于血药浓度峰值。

A simple HPLC UV method was established to determine concentrations of ketoprofen (KP) in rabbit plasma following oral administration. Twelve rabbits were selected and divided into three groups. KP β CD inclusion complex suspension, KP entity suspension (in 0 5% CMC Na) and 0 5% CMC Na suspension (as a placebo group) were administered orally to the three groups of rabbits, respectively. Differences in the pharmacokinetics pharmacodynamics (PK PD) parameters between KP β CD inclusion complex and KP entity were examined. The results indicate that the established HPLC UV method could be used to assay the concentrations of KP in rabbit plasma with good precision. The distribution phase T 1/2 α of the complexated KP was 0 4 h, while that of the KP entity was 0 56 h, KP in β CD inclusion complex could be absorbed more rapidly. The early effect values of the KP inclusion complex were higher than those of the KP entity. The maximal antipyretic effect occurred after the peak of plasma concentration. This phenomenon indicates that the effect compartment of ketoprofen is in the peripheral compartment.