Screening of mitragynine as inhibitors of CYP2C9 activity in HLM CSV JSON

Natural product: Kratom (Mitragyna speciosa)
Associated study: Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations

In Vitro Enzyme Inhibition Experiment

Screening of mitragynine as inhibitors of CYP2C9 activity in HLM

Inhibition was detected. Cutoff used —
50% inhibition at the highest tested concentration

Object compound

diclofenac 1124300

Precipitant

mitragynine

Object metabolite investigated

4'-hydroxydiclofenac

Enzymes involved in metabolite pathway

CYP2C9 4309227

Test system used

Cell fraction Pooled human liver microsomes -7999662

Results

Mitragynine and kratom extracts showed concentration-dependent inhibition of CYP activity in HLM. Mitragynine at 10 µM inhibited CYP2C9, CYP2D6, and CYP3A activity by 42%, 87%, and 50%, respectively. Kratom extracts at 20 µg/mL inhibited these activities by 81-88%, 87-93%, and 86-89%, respectively.

Sample	Compound measured	Value	Measurement	Study sequence	Additional information	N replicates

Experimental Conditions

Methanol (0.8 % v/v) served as solvent control. Sulphaphenazole (1 µM), quinidine (2 µM), and ketoconazole (0.01 µM) served as positive control inhibitors of CYP2C9, CYP2D6, and CYP3A, respectively.

Cell density

Protein concentration

0.05 mg/mL

Test system preparation

Commercially available

Test system lot number

1010191

Incubation volume

400 µL

Incubation time

10 min

Co-factors

NADPH

Protein linearity

Available

Time linearity

Available

Object concentrations tested

4 µM

Precipitant concentrations tested

1, 10, and 100 µM

NOTE

Screening of mitragynine as inhibitors of CYP2C9 activity in HLM CSV JSON

In Vitro Enzyme Inhibition Experiment

Inhibition was detected. Cutoff used — 50% inhibition at the highest tested concentration

Results

Experimental Conditions

Inhibition was detected. Cutoff used —
50% inhibition at the highest tested concentration