中枢神经系统药物转运体P-糖蛋白的表达水平变化对儿童药物代谢的影响

Effect of Drug Transporter P-glycoprotein Expressions in Central Nervous Systems on Drug Metabolism in Children

药物转运体P-糖蛋白属于结合盒式蛋白转运体蛋白家族,其可将小分子物质等排出大脑,有效地减少或阻止药物进入脑组织,从而发挥中枢神经系统保护作用。但对脑组织的药物转运体P-糖蛋白在新生儿出生后表达水平变化的研究较少。本文综述了药物转运体P-糖蛋白在中枢神经系统的外排转运功能、儿童中枢神经系统表达量变化、中枢神经系统发育早期阶段P-糖蛋白表达量对脑组织药物浓度的影响、动物外推至人类药代动力学模型以及内含P-糖蛋白的中枢神经系统生理药代动力学模型研究,为药物转运体P-糖蛋白底物在儿童生理药代动力学研究提供参考。

Drug transporter P-glycoprotein is a member of the ATP-binding cassette transporter family.P-glycoprotein is regarded as a selective gatekeeper of the blood brain barrier to prevent the entry of toxins or unwanted substances into the brain.There is little information available on the expression levels of P-glycoprotein in brain tissue in neonates.This article summarizes the efflux transport of P-glycoprotein,the expressions of P-glycoprotein in the central nervous system of children,the effect of P-glycoprotein expressions on drug concentrations in the brain during the early development of the central nervous system,related studies on physiologically based pharmacokinetic models extrapolated from animals to humans,and research on physiologically based pharmacokinetic models of the central nervous system containing P-glycoprotein.It is hoped that this study can contribute to studies on pharmacokinetics in children based on P-glycoprotein substrates.