OBJECTIVES: (1) To determine the pharmacokinetic parameters of alprazolam and its two metabolites in plasma from healthy volunteers; (2) to identify a suitable single time point to take a plasma sample for CYP3A phenotyping. METHODS: Twelve healthy Swedish volunteers received a single oral dose of 1 mg alprazolam. Blood samples were collected before drug intake and frequently up to 72 h thereafter. A liquid-chromatography/mass-spectrometry (LC/MS) method was used for the quantification of alprazolam, and 4- and alpha-hydroxyalprazolam. RESULTS: The interindividual variation in the area under the concentration-time curve (AUC) was two, three and fourfold for alprazolam, 4-hydroxyalprazolam and alpha-hydroxyalprazolam, respectively. Plasma concentration ratios collected between 1 h and 48 h for both alprazolam/4-hydroxyalprazolam and alprazolam/alpha-hydroxyalprazolam correlated significantly to the corresponding AUC0-infinity ratios. CONCLUSIONS: The metabolic ratios of alprazolam to respective metabolite in a single plasma sample at 3-24 h are suggested to reflect the alprazolam 4- and alpha-hydroxylation activities. In future, it will be important to study these activities in populations where CYP3A5, in addition to CYP3A4, is expressed at a high frequency and to clarify the relative importance of the two enzymatic pathways for in vivo clearance of alprazolam.
OBJECTIVES: (1) To determine the pharmacokinetic parameters of alprazolam and its two metabolites in plasma from healthy volunteers; (2) to identify a suitable single time point to take a plasma sample for CYP3A phenotyping. METHODS: Twelve healthy Swedish volunteers received a single oral dose of 1 mg alprazolam. Blood samples were collected before drug intake and frequently up to 72 h thereafter. A liquid-chromatography/mass-spectrometry (LC/MS) method was used for the quantification of alprazolam, and 4- and alpha-hydroxyalprazolam. RESULTS: The interindividual variation in the area under the concentration-time curve (AUC) was two, three and fourfold for alprazolam, 4-hydroxyalprazolam and alpha-hydroxyalprazolam, respectively. Plasma concentration ratios collected between 1 h and 48 h for both alprazolam/4-hydroxyalprazolam and alprazolam/alpha-hydroxyalprazolam correlated significantly to the corresponding AUC0-infinity ratios. CONCLUSIONS: The metabolic ratios of alprazolam to respective metabolite in a single plasma sample at 3-24 h are suggested to reflect the alprazolam 4- and alpha-hydroxylation activities. In future, it will be important to study these activities in populations where CYP3A5, in addition to CYP3A4, is expressed at a high frequency and to clarify the relative importance of the two enzymatic pathways for in vivo clearance of alprazolam.
Authors: N Yasui; T Kondo; H Furukori; S Kaneko; T Ohkubo; T Uno; T Osanai; K Sugawara; K Otani Journal: Psychopharmacology (Berl) Date: 2000-06 Impact factor: 4.530
Authors: E Hustert; M Haberl; O Burk; R Wolbold; Y Q He; K Klein; A C Nuessler; P Neuhaus; J Klattig; R Eiselt; I Koch; A Zibat; J Brockmöller; J R Halpert; U M Zanger; L Wojnowski Journal: Pharmacogenetics Date: 2001-12
Authors: D R Nelson; L Koymans; T Kamataki; J J Stegeman; R Feyereisen; D J Waxman; M R Waterman; O Gotoh; M J Coon; R W Estabrook; I C Gunsalus; D W Nebert Journal: Pharmacogenetics Date: 1996-02
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Authors: C M Hunt; P B Watkins; P Saenger; G M Stave; N Barlascini; C O Watlington; J T Wright; P S Guzelian Journal: Clin Pharmacol Ther Date: 1992-01 Impact factor: 6.875
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