title: Effect of CYP3A5*3 genotype on the pharmacokinetics and pharmacodynamics of alprazolam in healthy subjects.
abstract: OBJECTIVE
  Our objective was to evaluate the effect of the CYP3A5 genotype on the pharmacokinetics and pharmacodynamics of alprazolam in healthy volunteers.
  
  
  METHODS
  Nineteen healthy male volunteers were divided into 3 groups on the basis of the genetic polymorphism of CYP3A5. The groups comprised subjects with CYP3A5*1/*1 (n=5), CYP3A5*1/*3 (n=7), or CYP3A5*3/*3 (n=7). After a single oral 1-mg dose of alprazolam, plasma concentrations of alprazolam were measured up to 72 hours, together with assessment of psychomotor function by use of the Digit Symbol Substitution Test, according to CYP3A5 genotype.
  
  
  RESULTS
  The area under the plasma concentration-time curve for alprazolam was significantly greater in subjects with CYP3A5*3/*3 (830.5+/-160.4 ng . h/mL [mean+/-SD]) than in those with CYP3A5*1/*1 (599.9+/-141.0 ng . h/mL) (P=.030). The oral clearance of alprazolam was also significantly different between the CYP3A5*1/*1 group (3.5+/-0.8 L/h) and CYP3A5*3/*3 group (2.5+/-0.5 L/h) (P=.036). Although a trend was noted for the area under the Digit Symbol Substitution Test score change-time curve (area under the effect curve) to be greater in subjects with CYP3A5*3/*3 (177.2+/-84.6) than in those with CYP3A5*1/*1 (107.5+/-44), the difference did not reach statistical significance (P=.148).
  
  
  CONCLUSIONS
  The CYP3A5*3 genotype affects the disposition of alprazolam and thus influences the plasma levels of alprazolam.
authors.affiliation: Department of Pharmacology, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Park
authors.forename: Kyoung-Ah
authors.initials: KA
authors.lastname: Kim
authors.forename: Pil-Whan
authors.initials: PW
authors.lastname: Park
authors.forename: Ock-Je
authors.initials: OJ
authors.lastname: Lee
authors.forename: Dong-Kyun
authors.initials: DK
authors.lastname: Kang
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Shon
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Liu
authors.forename: Jae-Gook
authors.initials: JG
authors.lastname: Shin
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000525:Alprazolam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D044466:Asian People / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004247:DNA / Q000032:analysis; D017931:DNA Primers; D005838:Genotype; D006801:Humans; D007723:Korea; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012016:Reference Values
chemical_list: D014151:Anti-Anxiety Agents; D017931:DNA Primers; D004247:DNA; D051544:Cytochrome P-450 CYP3A; D000525:Alprazolam