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Effect of CYP3A5*3 genotype on the pharmacokinetics and pharmacodynamics of alprazolam in healthy subjects
Author(s) -
Park JiYoung,
Kim KyoungAh,
Park PilWhan,
Lee OckJe,
Kang DongKyun,
Shon JiHong,
Liu KwangHyun,
Shin JaeGook
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2006.02.008
Subject(s) - alprazolam , pharmacodynamics , pharmacokinetics , cyp3a5 , pharmacology , medicine , digit symbol substitution test , crossover study , area under the curve , genotype , biology , psychiatry , anxiety , placebo , genetics , alternative medicine , pathology , gene
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. Clinical Pharmacology & Therapeutics (2006) 79 , 590–599; doi: 10.1016/j.clpt.2006.02.008