关键词: 微透析, 支气管动脉灌注化疗, 卡铂, 药物代谢动力学

Abstract:

Objective In this study,microdialysis technique is adopted to sample and measure drug concentration in the lung tissue of dog accurately,and all kinds of pharmacokinetics parameters are calculated.The variation tendency between Bronchial Artery Infusion chemotherapy(BAI) and routine vein chemotherapy is compared.This study is expected to offer a reference basis for the determination of drug protocol of BAI in hope to improve its efficacy in clinical practice.Methods Experimental dogs were randomly divided into group BAI and group venous.At first,microdialysis probes were implanted into the lung under CT guidance.After selective catheterization of bronchial artery,Carboplatin(CBP) 200 mg was slowly infused into the target artery.In group venous same dosage of CBP were administered through a vein.Then dialysate samples were collected and assayed.Data were processed with 3P87 software,and pharmacokinetic parameters were calculated.Results The results showed that in both groups,variation tendencies of CBP in lung were fit for two open compartment model with absorbing phase,however,some pharmacokinetic parameters are different.Area Under Curve(AUC) value of CBP in group BAI((321.17±18.96)μg·L^-1·h) is significantly higher than group venous((185.75±33.21)μg·L^-1·h)(P<0.01).And Vc value of CBP in group BAI was remarkably smaller than group venous((13.81±3.35)mg·L·μg^-1) versus((31.25±2.66)mg·L·μg^-1,P<0.01). There are no significant difference of distribution rate constant α and distribution half-life t_l/2α between two groups.On the contrary,in group BAI elimination rate constant β and clearance(Cl) decrease obviously,and elimination half-life t_l/2β is prolonged distinctly.Conclusion Compared with intra-venous administration,BAI does not affect basic variation tendency of CBP,but did changes some pharmacokinetic parameters.BAI shortens the absorption phase of CBP and increases the peak concentration.BAI does not affect the distribution phase greatly,but significantly prolongs the elimination phase.It suggests that the BAI protocol should not be applied to systemic chemotherapy regime indiscriminately.

Key words: microdialysis, bronchial artery infusion chemotherapy, carboplatin, pharmacokinetics