Rosskopf D, Kroemer H K, Siegmund W
Abteilung für Allgemeine Pharmakologie, Institut für Pharmakologie, Ernst-Moritz-Arndt Universität, Greifswald.
Dtsch Med Wochenschr. 2009 Feb;134(8):345-56; quiz 357-60. doi: 10.1055/s-0028-1124005. Epub 2009 Feb 10.
Drug disposition is controlled by drug metabolism and drug transport. In the last decade numerous drug transporters have been identified and characterized in the context of drug uptake, efflux and interactions. This article reviews major advancements in this field. Efflux pumps like the multidrug resistance protein 1 (MDR1, ABCB1) are expressed in the intestine where they secrete drugs back into the intestinal lumen. Inhibitors of ABCB1 can increase the bioavailability of such drugs due to an increased absorption. Inducers of metabolism (rifampicin, carbamazepine, St. John's Wort) also induce the expression of drug transporters like ABCB1. Subsequently, an increased intestinal secretion in addition to an increased metabolism can diminish plasma levels of drugs, for example ciclosporin. The relevance of uptake transporters is increasingly recognized. SLCO1B1 is a hepatic uptake transporter involved in the absorption of statins. Inhibition of SLCO1B1 as well as common genetic variants can lead to increased bioavailability and to adverse reactions, ultimately culminating in rhabdomyolysis.
药物处置受药物代谢和药物转运的控制。在过去十年中，已在药物摄取、外排及相互作用方面鉴定并表征了众多药物转运体。本文综述了该领域的主要进展。像多药耐药蛋白1（MDR1，ABCB1）这样的外排泵在肠道中表达，它们将药物分泌回肠腔。ABCB1的抑制剂可因吸收增加而提高此类药物的生物利用度。代谢诱导剂（利福平、卡马西平、圣约翰草）也会诱导ABCB1等药物转运体的表达。随后，除代谢增加外，肠道分泌增加会降低药物的血浆水平，例如环孢素。摄取转运体的相关性日益得到认可。SLCO1B1是一种肝脏摄取转运体，参与他汀类药物的吸收。抑制SLCO1B1以及常见的基因变异可导致生物利用度增加和不良反应，最终导致横纹肌溶解。
