title: Assessment of a novel β2-adrenoceptor agonist, trantinterol, for interference with human liver cytochrome P450 enzymes activities.
abstract: The effect of a novel β(2)-adrenoceptor agonist, trantinterol on the activities of cytochrome P450 (CYP450) was investigated with human liver microsomes and human cryohepatocytes in order to assess the potential for drug-drug interactions. The ability of trantinterol to inhibit CYP450 activities was evaluated in vitro in human liver microsomes. Trantinterol did not inhibit CYP2C19, CYP2D6, and CYP3A4/5 (IC(50)>100 μM). It acted as a weak inhibitor of CYP1A2 and CYP2C9 with IC(50) of 70.8 and 81.9 μM, respectively. No time-dependent inhibitions were observed in the present research. To evaluate CYP450 induction, human cryohepatocytes (n=3) were used and treated once daily for 3 days with trantinterol (0.01, 0.1, and 1 ng/ml), after which CYP450 activities were measured. At concentration of 0.01 ng/ml, which is close to the C(max) at maximal recommended doses (50 μg), trantinterol was about 8% as effective as omeprazole (CYP1A2 inducer) only with donor 2. At concentration of 1 ng/ml, trantinterol was about 3.6 ± 3.1% as effective as rifampin (CYP3A4/5 inducer). These in vitro results indicated that, at pharmacological relevant concentrations, trantinterol will not produce clinically significant CYP450 inhibition or induction.
authors.affiliation: Department of Analytical Chemistry, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Jiang
authors.forename: Kunjie
authors.initials: K
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Qin
authors.forename: Xiumei
authors.initials: X
authors.lastname: Lu
authors.forename: Famei
authors.initials: F
authors.lastname: Li
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002976:Clenbuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D019388:Cytochrome P-450 CYP1A2 / Q000187:drug effects; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6 / Q000187:drug effects / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology*; D017711:Nonlinear Dynamics; D009853:Omeprazole / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology
chemical_list: D000322:Adrenergic Agonists; D065609:Cytochrome P-450 CYP1A2 Inhibitors; C542064:trantinterol; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C504573:CYP1A2 protein, human; C045793:CYP2C19 protein, human; C510164:CYP3A5 protein, human; D019388:Cytochrome P-450 CYP1A2; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D009853:Omeprazole; D012293:Rifampin; D002976:Clenbuterol