Journal: bioRxiv

Article Title: 3D Spheroid Primary Human Hepatocytes for Prediction of Cytochrome P450 and Drug Transporter Induction

doi: 10.1101/2022.10.30.514199

Figure Lengend Snippet: Spheroids were treated with inducers or vehicle (0.1% DMSO) or were untreated (No treatment) for 96 hours before incubation with the Basel cocktail (10 μM midazolam, 30 μM omeprazole, 20 μM efavirenz, 40 μM metoprolol, 30 μM losartan and 160 μM caffeine). The metabolic activities of CYP3A4, CYP2C19, CYP2B6 and CYP2D6 were measured from samples incubated for 8 hours or 0.5 hour in the case CYP2C19. Data were normalized to mean concentration of metabolites in the vehicle group and are presented as means of two hepatocyte donors. N = 2 hepatocyte donors each presented as a mean value of three biological replicates per condition. Dashed lines indicate a two-fold difference to the vehicle group.

Article Snippet: Omeprazole and efavirenz (Sigma-Aldrich) and midazolam (Toronto Research Chemicals, Toronto, ON, Canada) were dissolved in DMSO as 6,000x stocks.

Techniques: Incubation, Concentration Assay

Journal: Pharmaceutics

Article Title: Inhibitory Effect of AB-PINACA, Indazole Carboxamide Synthetic Cannabinoid, on Human Major Drug-Metabolizing Enzymes and Transporters

doi: 10.3390/pharmaceutics12111036

Figure Lengend Snippet: Inhibitory effects of AB-PINACA on metabolic activities of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 in ultrapooled human liver microsomes with (◯) and without (⚫) 30-min preincubation with NADPH at 37 °C. The cocktail CYP probes consist of set A (50 μM phenacetin, 2.5 μM coumarin, 2.0 μM amodiaquine, 10 μM diclofenac, 100 μM [ S ]-mephenytoin, 5.0 μM bufuralol, and 2.5 μM midazolam) and set B (50 μM bupropion). Data are means ±SD ( n = 3).

Article Snippet: AB-PINACA and midazolam were purchased from Cayman Chemical Company (Ann Arbor, MI, USA).

Techniques:

Journal: Pharmaceutics

Article Title: Inhibitory Effect of AB-PINACA, Indazole Carboxamide Synthetic Cannabinoid, on Human Major Drug-Metabolizing Enzymes and Transporters

doi: 10.3390/pharmaceutics12111036

Figure Lengend Snippet: IC 50 values of indazole carboxamide synthetic cannabinoid (AB-PINACA) for major cytochrome P450 (CYP) enzyme activities with and without 30-min preincubation with NADPH in ultrapooled human liver microsomes.

Article Snippet: AB-PINACA and midazolam were purchased from Cayman Chemical Company (Ann Arbor, MI, USA).

Techniques:

Journal: Pharmaceutics

Article Title: Inhibitory Effect of AB-PINACA, Indazole Carboxamide Synthetic Cannabinoid, on Human Major Drug-Metabolizing Enzymes and Transporters

doi: 10.3390/pharmaceutics12111036

Figure Lengend Snippet: ( A ) Inactivation kinetics of midazolam 1′-hydroxylation by AB-PINACA (5–100 μM) in ultrapooled human liver microsomes and ( B ) the relationships between the K obs values and the AB-PINACA concentrations for the determination of the K i and k inact values for time-dependent inhibition of CYP3A4 activity.

Article Snippet: AB-PINACA and midazolam were purchased from Cayman Chemical Company (Ann Arbor, MI, USA).

Techniques: Inhibition, Activity Assay