Validation of the plasma half-life of 11α-deuterium cortisol as a sensitive index for the analysis of human 11β-HSD2 activity in vivo

This study is concerned with validating the measurement of the plasma half-life of 11α-2H cortisol in an attempt to accurately assess the in vivo activity of 11β-HSD2 in man. Oral administration of 5 mg of cortisol-13C4,2H1 to a human subject after repeated ingestions of 130 mg/day of glycyrrhetinic acid for 5 days resulted in a decrease in the rate constant of the cortisol-13C4,2H1 to cortisone-13C4 conversion, a direct index reflecting 11β-HSD2 activity. The reduced 11β-HSD2 activity led to an increase in the elimination half-life of cortisol-13C4,2H1, indicating that the loss of 11α-2H is a sensitive in vivo means of assessing 11β-HSD2 activity. A simultaneous oral administration of 3 mg each of [1,2,4,19-13C4,11α-2H]cortisol (cortisol-13C4,2H1) and 11α-2H cortisol to another human subject confirmed the bioequivalency of the two labeled cortisols. The information obtained from the kinetic analysis of the 11β-HSD2-catalyzed conversion of cortisol-13C4,2H1 to cortisone-13C4 indicated that the elimination half-life of 11α-2H cortisol was a sensitive index of renal 11β-HSD2 activity. The use of 11α-2H cortisol as a tracer appears to offer a significant advance in evaluating human 11β-HSD2 activity in vivo.