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 clea rance and long elimination half-life of alprazolam and trazodone, two CYP3A substrate drugs, following single-dose oral administration in clinical pha rmacokinetic studies. Genomic DNA isolated from the individual's peripheral blood was subjected to polymerase chain reaction amplification and subsequ ent sequence analysis of a 592 base-pair segment upstream from the CYP3A co ding region. The analysis revealed no variation from wild-type in the nucle otide present at position -290, previously suggested to influence expressio n and/or activity of CYP3A. The functional significance of this promoter re gion mutation is unclear and requires further evaluation. Journal of Clinic al Pharmacology, 2000;40:200-204 (C)2000 the American College of Clinical P harmacology.