Change From the CYP2D6 Extensive Metabolizer to the Poor Metabolizer Phenotype During Treatment With Bupropion

Güzey, Cüneyt*; Norström, Åke†; Spigset, Olav*

*Department of Clinical Pharmacology, University Hospital, Trondheim, Norway, †Division of Clinical Pharmacology, Norrland University Hospital, Umeå, Sweden

Received September 4, 2001; accepted October 26, 2001.

Address correspondence and reprint requests to Olav Spigset, Department of Clinical Pharmacology, University Hospital, N-7006 Trondheim, Norway; E-mail: olav.spigset@legemidler.no

Summary:

Some data indicate that bupropion inhibits the cytochrome P-450 enzyme CYP2D6, but very little published data is available on the extent of this inhibition. The objective of the present study was to quantify this inhibition in a subject treated with bupropion for smoking cessation. Genotypically, the patient was a CYP2D6 homozygous extensive metabolizer (EM). His CYP2D6 phenotype was assessed using the test drug dextromethorphan before, during, and after treatment with bupropion. During treatment with bupropion, he clearly changed from the EM to the poor metabolizer (PM) phenotype. Although the results from a single patient should be interpreted with great caution, the extent of the interaction indicates that bupropion might be a CYP2D6 inhibitor as potent as the most powerful CYP2D6 inhibitors known, such as quinidine and paroxetine.