Stereoselective sulphate conjugation of racemic terbutaline by human liver cytosol

Br J Clin Pharmacol. 1990 Jul;30(1):127-33. doi: 10.1111/j.1365-2125.1990.tb03752.x.

Abstract

1. The enantioselectivity of the sulphation of racemic terbutaline by phenolsulphotransferases was examined in vitro using cytosol from human livers (n = 3) and [35S]-3'-phosphoadenosine-5'-phosphosulphate (PAP35S) as the sulphate donor. 2. The radioactive sulphate conjugate formed was isolated by h.p.l.c. and its enantiomers were separated intact by h.p.l.c. after chiral derivatization. 3. Sulphation of racemic terbutaline occurred with the same apparent Km value for both enantiomers (270 microM). The extent of sulphation of the (+)-enantiomer was double that of the (-)-enantiomer, solely due to a difference in their apparent Vmax values. 4. Sulphation of racemic prenalterol, a structural analogue of terbutaline, also showed a two-fold preference for the (+)-enantiomer. 5. These findings suggest that enantioselective sulphate conjugation of chiral phenolic sympathomimetic amine drugs may lead to enantioselective pharmacokinetics that should be considered in the clinical use of these drugs.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Cytosol / metabolism*
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Kinetics
  • Liver / metabolism*
  • Male
  • Middle Aged
  • Phosphoadenosine Phosphosulfate / metabolism
  • Proteins / metabolism
  • Stereoisomerism
  • Sulfates / metabolism*
  • Sulfur Radioisotopes
  • Temperature
  • Terbutaline / metabolism*

Substances

  • Proteins
  • Sulfates
  • Sulfur Radioisotopes
  • Phosphoadenosine Phosphosulfate
  • Terbutaline