慢性肾功能不全对药动学影响研究进展

慢性肾功能不全是临床常见疾病之一,主要经肾消除及主要经非肾途径消除的药物,药代动力学及药效学均受慢性肾功能不全疾病的影响。肾功能不全尤其是终末期肾病不仅直接减少药物的排泄,还能影响药物吸收、药物转运及药物代谢,从而影响药物的非肾消除。肾功能不全可直接抑制药物代谢酶及转运体的活性并减少酶及转运体在胃肠道、肝脏等多个器官的mRNA及蛋白的表达。引起这种抑制作用的原因尚不明确,血液透析可以部分抵消或逆转这种抑制作用并存在透析消除。

Advances of the influence of chronic renal failure on the pharmacokinetics

The chronic renal failure(CRF) is one of the common diseases in clinic. CRF affects the pharmacokinetics and pharmacodynamics of drug which either eliminate by renal or by nonrenal routes. The tests in vivo and in vitro demonstrated that renal impairment especially end-stage renal disease (ESRD) not only decreased the excretion by kidney, but also the alterations in the activities of and interplay between uptake and efflux transporters and metabolic enzymes significantly affected the PK disposition and resulting exposure of drugs cleared through nonrenal. CRF can directly inhibit the activity of various metabolic enzymes and transporters and in the other sides the CRF can down-regulate the mRNA and protein expression of metabolic enzymes and multiple intestinal and hepatic drug transporters. The reasons of those inhibition effects need more researches. The hemodialysis can partially offset or reverse this kinds of inhibition and dialysis clearance exist in the patient with ESRD.