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: Ultrapooled human liver microsomes (150 donors, mixed gender), LLC-PK1-MDR1 cells stably expressing P-gp, LLC-PK1-mock cells, HEK293-OAT1, -OAT3, -OCT1, -OCT2, -OATP1B1, and -OATP1B3 cells (HEK293 cells transiently overexpressing respective transporters), HEK293-mock cells, [ S ]-mephenytoin, 4′-hydroxymephenytoin, bufuralol, 1′-hydroxybufuralol, d 9 -1′-hydroxybufuralol, 1′-hydroxymidazolam, N -desethylamodiaquine, 4′-hydroxydiclofenac, 13 C 2 , 15 N-acetaminophen, medium 199, fetal bovine serum (FBS), collagen-coated 24-Transwell plates, and poly- d -lysine-coated 96-well plates were purchased from Corning Life Sciences (Woburn, MA, 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: Ultrapooled human liver microsomes (150 donors, mixed gender), LLC-PK1-MDR1 cells stably expressing P-gp, LLC-PK1-mock cells, HEK293-OAT1, -OAT3, -OCT1, -OCT2, -OATP1B1, and -OATP1B3 cells (HEK293 cells transiently overexpressing respective transporters), HEK293-mock cells, [ S ]-mephenytoin, 4′-hydroxymephenytoin, bufuralol, 1′-hydroxybufuralol, d 9 -1′-hydroxybufuralol, 1′-hydroxymidazolam, N -desethylamodiaquine, 4′-hydroxydiclofenac, 13 C 2 , 15 N-acetaminophen, medium 199, fetal bovine serum (FBS), collagen-coated 24-Transwell plates, and poly- d -lysine-coated 96-well plates were purchased from Corning Life Sciences (Woburn, MA, 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: Lineweaver–Burk (left panel) and Dixon (right panel) plots for the inhibitory effects of AB-PINACA (1–40 μM) on ( A ) CYP2C8, ( B ) CYP2C9, and ( C ) CYP2C19 activities in the presence of varying concentrations of substrates, amodiaquine (1, 2, 4, and 8 μM), diclofenac (2, 5, 10, and 20 μM), or [ S ]-mephenytoin (20, 40, 80, and 160 μM) in ultrapooled human liver microsomes. Data are means ± SD ( n = 3).

Article Snippet: Ultrapooled human liver microsomes (150 donors, mixed gender), LLC-PK1-MDR1 cells stably expressing P-gp, LLC-PK1-mock cells, HEK293-OAT1, -OAT3, -OCT1, -OCT2, -OATP1B1, and -OATP1B3 cells (HEK293 cells transiently overexpressing respective transporters), HEK293-mock cells, [ S ]-mephenytoin, 4′-hydroxymephenytoin, bufuralol, 1′-hydroxybufuralol, d 9 -1′-hydroxybufuralol, 1′-hydroxymidazolam, N -desethylamodiaquine, 4′-hydroxydiclofenac, 13 C 2 , 15 N-acetaminophen, medium 199, fetal bovine serum (FBS), collagen-coated 24-Transwell plates, and poly- d -lysine-coated 96-well plates were purchased from Corning Life Sciences (Woburn, MA, 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: Ultrapooled human liver microsomes (150 donors, mixed gender), LLC-PK1-MDR1 cells stably expressing P-gp, LLC-PK1-mock cells, HEK293-OAT1, -OAT3, -OCT1, -OCT2, -OATP1B1, and -OATP1B3 cells (HEK293 cells transiently overexpressing respective transporters), HEK293-mock cells, [ S ]-mephenytoin, 4′-hydroxymephenytoin, bufuralol, 1′-hydroxybufuralol, d 9 -1′-hydroxybufuralol, 1′-hydroxymidazolam, N -desethylamodiaquine, 4′-hydroxydiclofenac, 13 C 2 , 15 N-acetaminophen, medium 199, fetal bovine serum (FBS), collagen-coated 24-Transwell plates, and poly- d -lysine-coated 96-well plates were purchased from Corning Life Sciences (Woburn, MA, USA).

Techniques: Inhibition, Activity 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 UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, and UGT2B7 in ultrapooled human liver microsomes. The cocktail UGT probes consist of A set (0.5 µM SN-38, 2 µM chenodeoxycholic acid, and 0.5 µM trifluoperazine) and B set (1 µM N -acetylserotonin; 0.2 µM mycophenolic acid, and 1 µM naloxone). Data are means ± SD ( n = 3).

Article Snippet: Ultrapooled human liver microsomes (150 donors, mixed gender), LLC-PK1-MDR1 cells stably expressing P-gp, LLC-PK1-mock cells, HEK293-OAT1, -OAT3, -OCT1, -OCT2, -OATP1B1, and -OATP1B3 cells (HEK293 cells transiently overexpressing respective transporters), HEK293-mock cells, [ S ]-mephenytoin, 4′-hydroxymephenytoin, bufuralol, 1′-hydroxybufuralol, d 9 -1′-hydroxybufuralol, 1′-hydroxymidazolam, N -desethylamodiaquine, 4′-hydroxydiclofenac, 13 C 2 , 15 N-acetaminophen, medium 199, fetal bovine serum (FBS), collagen-coated 24-Transwell plates, and poly- d -lysine-coated 96-well plates were purchased from Corning Life Sciences (Woburn, MA, USA).

Techniques: