scholarly journals P-glycoprotein- and organic anion-transporting polypeptide-mediated transport of periplocin may lead to drug–herb/drug–drug interactions

2014 ◽  
pp. 475 ◽  
Author(s):  
Xin He ◽  
Sheng Liang ◽  
Fengchun Deng ◽  
Haiyan Xing ◽  
He Wen ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Organic Anion ◽  
Organic Anion Transporting Polypeptide ◽  
P Glycoprotein

scholarly journals In Vitro Interaction of AB-FUBINACA with Human Cytochrome P450, UDP-Glucuronosyltransferase Enzymes and Drug Transporters

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4589 ◽  
Author(s):  
Sunjoo Kim ◽  
Dong Kyun Kim ◽  
Yongho Shin ◽  
Ji-Hyeon Jeon ◽  
Im-Sook Song ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Organic Anion ◽  
Liver Microsomes ◽  
Drug Abusers ◽  
Cancer Resistance ◽  
Mixed Inhibition ◽  
P Glycoprotein ◽  
Human Cytochrome

AB-FUBINACA, a synthetic indazole carboxamide cannabinoid, has been used worldwide as a new psychoactive substance. Because drug abusers take various drugs concomitantly, it is necessary to explore potential AB-FUBINACA-induced drug–drug interactions caused by modulation of drug-metabolizing enzymes and transporters. In this study, the inhibitory effects of AB-FUBINACA on eight major human cytochrome P450s (CYPs) and six uridine 5′-diphospho-glucuronosyltransferases (UGTs) of human liver microsomes, and on eight clinically important transport activities including organic cation transporters (OCT)1 and OCT2, organic anion transporters (OAT)1 and OAT3, organic anion transporting polypeptide transporters (OATP)1B1 and OATP1B3, P-glycoprotein, and breast cancer resistance protein (BCRP) in transporter-overexpressing cells were investigated. AB-FUBINACA inhibited CYP2B6-mediated bupropion hydroxylation via mixed inhibition with Ki value of 15.0 µM and competitively inhibited CYP2C8-catalyzed amodiaquine N-de-ethylation, CYP2C9-catalyzed diclofenac 4′-hydroxylation, CYP2C19-catalyzed [S]-mephenytoin 4′-hydroxylation, and CYP2D6-catalyzed bufuralol 1′-hydroxylation with Ki values of 19.9, 13.1, 6.3, and 20.8 µM, respectively. AB-FUBINACA inhibited OCT2-mediated MPP+ uptake via mixed inhibition (Ki, 54.2 µM) and competitively inhibited OATP1B1-mediated estrone-3-sulfate uptake (Ki, 94.4 µM). However, AB-FUBINACA did not significantly inhibit CYP1A2, CYP2A6, CYP3A4, UGT1A1, UGT1A3, UGT1A4, UGT1A6, or UGT2B7 enzyme activities at concentrations up to 100 µM. AB-FUBINACA did not significantly inhibit the transport activities of OCT1, OAT1/3, OATP1B3, P-glycoprotein, or BCRP at concentrations up to 250 μM. As the pharmacokinetics of AB-FUBINACA in humans and animals remain unknown, it is necessary to clinically evaluate potential in vivo pharmacokinetic drug–drug interactions induced by AB-FUBINACA-mediated inhibition of CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, OCT2, and OATP1B1 activities.

Pitavastatin as an In Vivo Probe for Studying Hepatic Organic Anion Transporting Polypeptide-Mediated Drug–Drug Interactions in Cynomolgus Monkeys

2013 ◽  
Vol 41 (10) ◽  
pp. 1875-1882 ◽  
Author(s):  
Tsuyoshi Takahashi ◽  
Tatsuyuki Ohtsuka ◽  
Takahiro Yoshikawa ◽  
Ichiro Tatekawa ◽  
Yasuhiro Uno ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Organic Anion ◽  
Cynomolgus Monkeys ◽  
Organic Anion Transporting Polypeptide

scholarly journals Glycyrrhizin has a high likelihood to be a victim of drug-drug interactions mediated by hepatic organic anion-transporting polypeptide 1B1/1B3

2018 ◽  
Vol 175 (17) ◽  
pp. 3486-3503 ◽  
Author(s):  
Jiajia Dong ◽  
Olajide E Olaleye ◽  
Rongrong Jiang ◽  
Jing Li ◽  
Chuang Lu ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Organic Anion ◽  
High Likelihood ◽  
Organic Anion Transporting Polypeptide
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