Inhibition kinetics of CYP2D6 activity by mitragynine 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

Inhibition kinetics of CYP2D6 activity by mitragynine in HLM

Inhibition was detected. Cutoff used —
N/A

Object compound

dextromethorphan 1119510

Precipitant

mitragynine

Object metabolite investigated

dextrorphan 4349487

Enzymes involved in metabolite pathway

CYP2D6 4173631

Test system used

Cell fraction Pooled human liver microsomes -7999662

Results

Mitragynine was shown to be a strong competitive inhibitor of CYP2D6 activity, with a K_iof 0.97 ± 0.07 µM, 1.25 ± 0.09 µM, and 0.95 ± 0.11 µM, respectively, for three individual experiments. [K_i(Mean ± SEM) values were determined using nonlinear least-squares regression and competitive inhibition model.]

Sample	Compound measured	Value	Measurement	Study sequence	Additional information	N replicates

Experimental Conditions

Methanol (0.8 % v/v) served as solvent control. Quinidine (2 µM) served as positive control inhibitors of CYP2D6 activity.

Cell density

Protein concentration

0.05 MG/ML

Test system preparation

Commercially available

Test system lot number

1010191

Incubation volume

200 µL

Incubation time

10 min

Co-factors

NADPH

Protein linearity

Available

Time linearity

Available

Precipitant concentrations tested

0.12 - 10 µM

NOTE

Inhibition kinetics of CYP2D6 activity by mitragynine in HLM CSV JSON

In Vitro Enzyme Inhibition Experiment

Inhibition was detected. Cutoff used — N/A

Results

Experimental Conditions

Inhibition was detected. Cutoff used —
N/A