Letters to the Editor
Reply: Methylphenidate and the Cytochrome P450 System
Dear Editor:
I thank Dr Baird for his valuable comments. Indeed, it has been confirmed that CYP2B6 is the principal enzyme involved in the hydroxylation of bupropion (1). Reports regarding the effect of methylphenidate (MPH) on the cytochrome P450 (CYP450) system are sparse, and to date, inhibition of CYP2B6 by MPH remains unproven. However, in vitro MPH inhibition of CYP2D1 and CYP2D has been demonstrated (2), and animal studies have shown inhibition of CYP1A, CYP2E1, and CYP3A by MPH (3). I agree with Dr Baird’s suggestion that other isozymes of the CYP450 system may also affected by MPH; nevertheless, scientific evidence endorsing this hypothesis is not yet available.
Further studies are necessary to define the possible drug interactions of MPH with drugs metabolized by CYP450.
With the information available, we can prudently state that clinical practice requires caution when coadministering MPH and bupropion, as well as when combining MPH with other medications that are CYP450 substrates.
References
1. Hesse LM, Venkatakrishnan K, Court MH, von Moltke LL, Duan SX, Shader RI, Greenblatt DJ. CYP2B6 mediates the in vitro hydroxylation of bupropion: potential drug interactions with other antidepressants. Drug Metabolism and Disposition 2000;28:1176–83.
2. Tyndale RF, Sunohara R, Inaba T, Kalow W, Gonzales FJ, Niznik HB. Neuronal cytochrome P450IIDI (Debrisoquine/sparteine-type) potent inhibition of activity by (-)-cocaine and nucleotide sequence identity to human hepatic P450 gene CYP2D6. Mol Pharmacol 1991;40:63–8.
3.Le Nedelec MJ, Rosengren RJ. Methylphenidate inhibits cytochrome P450 in the Swiss Webster mouse. Hum Exp Toxicol 2002;21:273–80.
Abel Ickowicz MD, FRCPC
Toronto, Ontario
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