Octreotide inhibits the bilirubin carriers organic anion transporting polypeptides 1B1 and 1B3 and the multidrug resistance-associated protein 2

The Journal of Pharmacology and Experimental Therapeutics
Michele VisentinGerd A Kullak-Ublick

Abstract

The somatostatin analog octreotide can lead to hyperbilirubinemia without evidence of liver injury. Here we investigate whether octreotide inhibits the main sinusoidal/canalicular bilirubin carriers and whether it is a transport substrate. Octreotide showed the most potent inhibitory effect toward OATP1B1-mediated transport and weaker inhibition for OATP1B3- and MRP2-mediated transport. Octreotide had no effect on OATP2B1-mediated transport. Octreotide inhibited [(3)H]estradiol-17-β-glucuronide (E17βG) influx mediated by OATP1B1, 1B3, and multidrug resistance-associated protein 2 (MRP2) in a concentration-dependent manner, and the IC50 values were computed to be 23 μM (95% confidence interval [CI] 18-29), 68 μM (95% CI 50-91), and 116.6 μM (95% CI 74.5-182.4), respectively. The interaction between octreotide and OATP1B1 was further studied. Inhibition of [(3)H]E17βG OATP1B1-mediated transport was purely competitive with no changes in maximum transport capacity (Vmax) and a twofold Km increase when the influx kinetics of [(3)H]E17βG were measured in the presence of octreotide (8.8 ± 3.1 versus 4.4 ± 1.2 μM, P = 0.03). The inhibition constant (Ki) of octreotide for the transport of [(3)H]E17βG was calculated at 33.5 ± 5.5 μM. Upt...Continue Reading

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Citations

Jul 13, 2016·Antimicrobial Agents and Chemotherapy·Zhibo GaiGerd A Kullak-Ublick
Oct 8, 2017·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Michele VisentinGerd A Kullak-Ublick
May 26, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Michele VisentinGerd A Kullak-Ublick
Sep 26, 2017·Therapeutic Delivery·Sarinj Fattah, David J Brayden
Aug 14, 2019·Liver International : Official Journal of the International Association for the Study of the Liver·Tämer El SaadanyGerd A Kullak-Ublick
Oct 9, 2019·Antimicrobial Agents and Chemotherapy·Sophia L SamodelovGerd A Kullak-Ublick
Aug 17, 2020·Pharmaceutics·Péter Tátrai, Péter Krajcsi
Feb 15, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zhibo GaiMichele Visentin
Oct 19, 2019·The Journal of Pharmacology and Experimental Therapeutics·Severin HörmannMichele Visentin
Aug 28, 2020·The Journal of Pharmacology and Experimental Therapeutics·Evelin KrajncGerd A Kullak-Ublick
Nov 28, 2019·Journal of Medicinal Chemistry·Wesley WangChristopher G Parker

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