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In vitro evaluation of potential drug interactions mediated by cytochrome P450 and transporters for luseogliflozin, an SGLT2 inhibitor.
Xenobiotica. 2017 Apr; 47(4):314-323.X

Abstract

1. We evaluated potential in vitro drug interactions of luseogliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, mediated by CYP inhibition, CYP induction and drug transporters using human liver microsomes, primary hepatocytes and recombinant cells-expressing efflux or uptake transporters, respectively. 2. Human CYP inhibition studies indicated that luseogliflozin was a weak inhibitor for CYP2C19 with an IC50 value of 58.3 μM, whereas it was not an inhibitor of the other eight major isoforms that were tested. The exposure of primary hepatocytes to luseogliflozin for 72 hrs weakly induced CYP3A4 at a concentration of 10 μM, whereas it did not induce CYP1A2 or CYP2B6 at concentrations of 0.1-10 μM. 3. An in vitro transport study suggested that luseogliflozin is a substrate for human P-glycoprotein (P-gp), but not for breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1 and OATP1B3, organic anion transporter (OAT) 1 and OAT3, or organic cation transporter (OCT) 2. Luseogliflozin weakly inhibited OATP1B3 with an IC50 value of 93.1 μM, but those for other transporters are greater than 100 μM. 4. Based on the therapeutic plasma concentration of the drug, clinically relevant drug interactions are unlikely to occur between luseogliflozin and coadministered drugs mediated by CYPs and/or transporters.

Authors+Show Affiliations

a Drug Safety and Pharmacokinetics Laboratories, Taisho Pharmaceutical Co., Ltd. , Saitama , Japan and.a Drug Safety and Pharmacokinetics Laboratories, Taisho Pharmaceutical Co., Ltd. , Saitama , Japan and.a Drug Safety and Pharmacokinetics Laboratories, Taisho Pharmaceutical Co., Ltd. , Saitama , Japan and.a Drug Safety and Pharmacokinetics Laboratories, Taisho Pharmaceutical Co., Ltd. , Saitama , Japan and.a Drug Safety and Pharmacokinetics Laboratories, Taisho Pharmaceutical Co., Ltd. , Saitama , Japan and.a Drug Safety and Pharmacokinetics Laboratories, Taisho Pharmaceutical Co., Ltd. , Saitama , Japan and.b Development Headquarters, Taisho Pharmaceutical Co., Ltd. , Tokyo , Japan.a Drug Safety and Pharmacokinetics Laboratories, Taisho Pharmaceutical Co., Ltd. , Saitama , Japan and.a Drug Safety and Pharmacokinetics Laboratories, Taisho Pharmaceutical Co., Ltd. , Saitama , Japan and.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27324291

Citation

Chino, Yukihiro, et al. "In Vitro Evaluation of Potential Drug Interactions Mediated By Cytochrome P450 and Transporters for Luseogliflozin, an SGLT2 Inhibitor." Xenobiotica; the Fate of Foreign Compounds in Biological Systems, vol. 47, no. 4, 2017, pp. 314-323.
Chino Y, Hasegawa M, Fukasawa Y, et al. In vitro evaluation of potential drug interactions mediated by cytochrome P450 and transporters for luseogliflozin, an SGLT2 inhibitor. Xenobiotica. 2017;47(4):314-323.
Chino, Y., Hasegawa, M., Fukasawa, Y., Mano, Y., Bando, K., Miyata, A., Nakai, Y., Endo, H., & Yamaguchi, J. I. (2017). In vitro evaluation of potential drug interactions mediated by cytochrome P450 and transporters for luseogliflozin, an SGLT2 inhibitor. Xenobiotica; the Fate of Foreign Compounds in Biological Systems, 47(4), 314-323. https://doi.org/10.1080/00498254.2016.1193913
Chino Y, et al. In Vitro Evaluation of Potential Drug Interactions Mediated By Cytochrome P450 and Transporters for Luseogliflozin, an SGLT2 Inhibitor. Xenobiotica. 2017;47(4):314-323. PubMed PMID: 27324291.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro evaluation of potential drug interactions mediated by cytochrome P450 and transporters for luseogliflozin, an SGLT2 inhibitor. AU - Chino,Yukihiro, AU - Hasegawa,Masatoshi, AU - Fukasawa,Yoshiki, AU - Mano,Yoko, AU - Bando,Kagumi, AU - Miyata,Atsunori, AU - Nakai,Yasuhiro, AU - Endo,Hiromi, AU - Yamaguchi,Jun-Ichi, Y1 - 2016/06/20/ PY - 2016/6/22/pubmed PY - 2017/7/18/medline PY - 2016/6/22/entrez KW - CYP KW - SGLT2 inhibitor KW - diabetes mellitus KW - induction KW - inhibition KW - transporter SP - 314 EP - 323 JF - Xenobiotica; the fate of foreign compounds in biological systems JO - Xenobiotica VL - 47 IS - 4 N2 - 1. We evaluated potential in vitro drug interactions of luseogliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, mediated by CYP inhibition, CYP induction and drug transporters using human liver microsomes, primary hepatocytes and recombinant cells-expressing efflux or uptake transporters, respectively. 2. Human CYP inhibition studies indicated that luseogliflozin was a weak inhibitor for CYP2C19 with an IC50 value of 58.3 μM, whereas it was not an inhibitor of the other eight major isoforms that were tested. The exposure of primary hepatocytes to luseogliflozin for 72 hrs weakly induced CYP3A4 at a concentration of 10 μM, whereas it did not induce CYP1A2 or CYP2B6 at concentrations of 0.1-10 μM. 3. An in vitro transport study suggested that luseogliflozin is a substrate for human P-glycoprotein (P-gp), but not for breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1 and OATP1B3, organic anion transporter (OAT) 1 and OAT3, or organic cation transporter (OCT) 2. Luseogliflozin weakly inhibited OATP1B3 with an IC50 value of 93.1 μM, but those for other transporters are greater than 100 μM. 4. Based on the therapeutic plasma concentration of the drug, clinically relevant drug interactions are unlikely to occur between luseogliflozin and coadministered drugs mediated by CYPs and/or transporters. SN - 1366-5928 UR - https://www.unboundmedicine.com/medline/citation/27324291/In_vitro_evaluation_of_potential_drug_interactions_mediated_by_cytochrome_P450_and_transporters_for_luseogliflozin_an_SGLT2_inhibitor_ L2 - http://www.tandfonline.com/doi/full/10.1080/00498254.2016.1193913 DB - PRIME DP - Unbound Medicine ER -