Pharmacokinetic and dynamic correlates of intravenous alprazolam challenge

The concentration-effect relationship of alprazolam plasma concentration and growth hormone changes was studied in six healthy volunteers by use of three different intravenous bolus doses of alprazolam (0.003, 0.007, and 0.02 mg/kg) in a random blind order. There was a linear increase in peak concentration (Cmax) and area under the curve (AUC) of alprazolam with increasing dose (r = 0.96). There was no significant correlation between alprazolam Cmax and effect on growth hormone measured as either maximum increase or maximum percentage change from baseline. There was, however, an overall positive correlation (r = 0.58) between the AUC values of alprazolam and growth hormone from 0 to 120 minutes, although the relative degree of increased AUC of growth hormone with increasing AUC of alprazolam varied greatly across individuals. The difficulties of interpreting the mechanisms underlying differential growth hormone responses even when concentration of stimulus is controlled are discussed.