Screening of mitragynine as inhibitors CYP3A activity in HIM 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 CYP3A activity in HIM

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

Object compound

midazolam 708298

Precipitant

mitragynine

Object metabolite investigated

1'-hydroxymidazolam

Enzymes involved in metabolite pathway

CYP3A

Test system used

Cell fraction Pooled human intestinal microsomes -7999663

Results

Mitragynine and kratom extracts showed concentration-dependent inhibition of CYP3A activity in HIM. Mitragynine at 10 µM inhibited CYP3A activity by 44%. Kratom extracts at 20 µg/mL inhibited CYP3A activity by 82-90%.

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

1610314

Incubation volume

400 µL

Incubation time

10 min

Co-factors

NADPH

Protein linearity

Available

Time linearity

Available

Object concentrations tested

2 µM

Precipitant concentrations tested

1, 10, and 100 µM

NOTE

Screening of mitragynine as inhibitors CYP3A activity in HIM 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