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  • Title: No correlations between the urinary ratio of 6beta-hydroxycortisol to free cortisol and pharmacokinetics of alprazolam.
    Author: Yasui-Furukori N, Kondo T, Kubota T, Otake H, Ohkubo T, Nagasaki T, Sugawara K, Chiba K, Otani K, Kaneko S.
    Journal: Eur J Clin Pharmacol; 2001 Jul; 57(4):285-8. PubMed ID: 11549205.
    Abstract:
    OBJECTIVE: The urinary ratio of 6beta-hydroxycortisol to cortisol is known as a possible marker of CYP3A4 activity. We investigated the correlation between this ratio and the disposition of alprazolam, which is a substrate of CYP3A4. METHODS: Twelve healthy volunteers took a single dose (0.8 mg) of alprazolam at 0800 hours. Blood samplings were conducted up to 48 h after the dosing. Urine was collected during the 24 h prior to dosing. Quantification of alprazolam in plasma and that of cortisol and 6beta-hydroxycortisol in urine was performed using high-performance liquid chromatography. RESULTS: Mean (+/-SD) values of peak plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve [AUC(0-48)] and elimination half-life (tl/2) of alprazolam were 12.0+/-3.0 ng/ml, 1.5+/-0.9 h, 200+/-41 ng/ml h and 16.0+/-4.3 h, respectively. Mean (+/-SD) urinary ratio of 6beta-hydroxycortisol to cortisol was 3.28+/-0.67. No significant correlations were found between urinary ratio of 6beta-hydroxycortisol to cortisol and any pharmacokinetic parameters of alprazolam (Cmax: rs= -0.06; tmax: r(s)= 0.34; AUC(0-48): rs=0.08; t1/2: r(s)= -0.36). CONCLUSION: This study suggests that the urinary ratio of 6beta-hydroxycortisol to cortisol is unlikely to predict pharmacokinetics of alprazolam.
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