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

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.