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Re: Atomoxetine: NMDA receptor antagonist

Posted by linkadge on July 25, 2020, at 11:49:56

In reply to Re: Atomoxetine: NMDA receptor antagonist, posted by undopaminergic on July 25, 2020, at 8:24:26

According to the study, a twice-daily dose 2045 mg of ATX, Cmax detected ranged from 174 to 1221 ng/ml. **This is a total daily dose of 40 - 90mg.

1) This is in adolescents (concentrations would be lower in adults taking equivalent doses).

2) Poor metabolizers have much higher blood levels than the normal metabolizers. This is why there is almost a 10x difference in concentration range.

To go from ng/mL --> uMol / L you just divide by the molar mass of atomoxetine (255).

40-90 mg (total) daily dose produced concentrations of 174 to 1221 ng/mL.

174ng/mL 255 g/mol = 0.68uM
1221ng/mL 255 g/mol = 4.78uM

Thus, a 90mg daily dose in poor metabolizing adolescents could result in a concentration of 4.78uM. This would be a level where *some* of the negative effects could be observed (there was a small increase in cell death between 1-5 uM). However, the more pronounced negative effects required 10-50 uM concentrations. This would require (much) higher doses. That being said, an non-poor metabolizing adult taking < 90mg would be expected to have *much* lower concentrations (possibly more than 10x lower for normal metabolizers). So, all this being said, you could get a genotype test to see if you are a low CYP2D6 (I think it is) metabolizer. If you were, then a 50mg dose could be on the threshold of some mild negative effects. If not, then the concentration would be far below the test concentrations used.

The first question to ask is whether the drug is helping you. If it isn't then case closed. If it is helping you, then consider the dose and, if you're really concerned, think about getting a metabolism genotype test. This would give you an idea of the concentration.





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