No correlations between the urinary ratio of 6 beta-hydroxycortisol to free cortisol and pharmacokinetics of alprazolam

Objective: The urinary ratio of 6 beta -hydroxycortisol to cortisol is know n 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 alprazola m 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 al prazolam in plasma and that of cortisol and 6 beta -hydroxycortisol in urin e was performed using high-performance liquid chromatography, Results: Mean ( SID) values of peak plasma concentration (C-max), time to C -max (t(max)), area under the plasma concentration-time curve [AUC(0-48)] a nd elimination half-life (t(1/2)) 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 6 beta -hydroxycortisol to cortisol was 3.28 +/- 0.67. N o significant correlations were found between urinary ratio of 6 beta -hydr oxycortisol to cortisol and any pharmacokinetic parameters of alprazolam (C -max: r(s) = -0.06; t(max): r(s) = 0.34; AUC(0 48): r(s)=0.08; t(1/2): r(s) =-0.36). Conclusion: This study suggests that the urinary ratio of 6 beta -hydroxyco rtisol to cortisol is unlikely to predict pharmacokinetics of alprazolam.