- Natural product: Kratom (Mitragyna speciosa)
- Associated study: Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations
In Vitro Enzyme Inhibition Experiment
IC50 shift determination for mitragynine towards CYP3A activity in HLM with NADPH
Inhibition was detected. Cutoff used —
IC50<10 µM for reversible inhibition and IC50shift ≥1.5 fold for time dependent inhibition
Cell fraction Pooled human liver microsomes -7999662
|Sample||Compound measured||Value||Measurement||Study sequence||Additional information||N replicates|
A cocktail of probe substrates for CYP2C9 (diclofenac), CYP2D6 (dextromethorphan), and CYP3A (midazolam) was used for the IC50shift determination.
Methanol (0.8 % v/v) served as solvent control. Tienilic acid (0.4 and 0.8 µM), paroxetine (0.25 and 0.5 µM), and 6',7'-dihydroxybergamottin (1 and 2 µM) served as positive control inhibitors of CYP2C9, CYP2D6, and CYP3A activities, respectively.
NADPH with precipitant
0.015 - 100 µM