Unusually Low Clearance of Two CYP3A Substrates, Alprazolam and Trazodone, in a Volunteer Subject with Wild-Type CYP3A4 Promoter Region

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Abstract
A healthy 40-year-old Caucasian male volunteer displayed unusually low clearance and long elimination half-life of alprazolam and trazodone, two CYP3A substrate drugs, following single-dose oral administration in clinical pharmacokinetic studies. Genomic DNA isolated from the individual's peripheral blood was subjected to polymerase chain reaction amplification and subsequent sequence analysis of a 592 base-pair segment upstream from the CYP3A coding region. The analysis revealed no variation from wild-type in the nucleotide present at position -290, previously suggested to influence expression and/or activity of CYP3A. The functional significance of this promoter region mutation is unclear and requires further evaluation.