title: Validation of the plasma half-life of 11alpha-deuterium cortisol as a sensitive index for the analysis of human 11beta-HSD2 activity in vivo.
abstract: This study is concerned with validating the measurement of the plasma half-life of 11alpha-(2)H cortisol in an attempt to accurately assess the in vivo activity of 11beta-HSD2 in man. Oral administration of 5mg of cortisol-(13)C(4),(2)H(1) to a human subject after repeated ingestions of 130mg/day of glycyrrhetinic acid for 5 days resulted in a decrease in the rate constant of the cortisol-(13)C(4),(2)H(1) to cortisone-(13)C(4) conversion, a direct index reflecting 11beta-HSD2 activity. The reduced 11beta-HSD2 activity led to an increase in the elimination half-life of cortisol-(13)C(4),(2)H(1), indicating that the loss of 11alpha-(2)H is a sensitive in vivo means of assessing 11beta-HSD2 activity. A simultaneous oral administration of 3mg each of [1,2,4,19-(13)C(4),11alpha-(2)H]cortisol (cortisol-(13)C(4),(2)H(1)) and 11alpha-(2)H cortisol to another human subject confirmed the bioequivalency of the two labeled cortisols. The information obtained from the kinetic analysis of the 11beta-HSD2-catalyzed conversion of cortisol-(13)C(4),(2)H(1) to cortisone-(13)C(4) indicated that the elimination half-life of 11alpha-(2)H cortisol was a sensitive index of renal 11beta-HSD2 activity. The use of 11alpha-(2)H cortisol as a tracer appears to offer a significant advance in evaluating human 11beta-HSD2 activity in vivo.
authors: Department of Medicinal Chemistry and Clinical Pharmacy, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. kasuyay@ps.toyaku.ac.jp
authors: Yasuji
authors: Y
authors: Kasuya
authors: Akitimo
authors: A
authors: Yokokawa
authors: Kouichi
authors: K
authors: Hamura
authors: Hiromi
authors: H
authors: Shibasaki
authors: Takashi
authors: T
authors: Furuta
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism*; D000284:Administration, Oral; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001711:Biotransformation / Q000187:drug effects / Q000502:physiology; D003903:Deuterium / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male
chemical_list: D000893:Anti-Inflammatory Agents; D003903:Deuterium; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human; D006854:Hydrocortisone