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Pharmacokinetics of pentobarbital enantiomers as determined by enantioselective radioimmunoassay after administration of racemate to humans and rabbits.

Publication ,  Journal Article
Cook, CE; Seltzman, TB; Tallent, CR; Lorenzo, B; Drayer, DE
Published in: J Pharmacol Exp Ther
June 1987

Radioimmunoassays were developed for R- and S-pentobarbital. The optical isomers of pentobarbital were individually alkylated to N-crotonic acid analogs that were coupled to bovine serum albumin. Immunization of rabbits with the conjugates, which were enantiomerically pure at the asymmetric' carbon of the pentobarbital moiety, led to formation of antisera that selectively bound the predicted enantiomer. In displacement studies with enantiomerically pure radioligands, the opposite enantiomer showed 1.0 to 1.4% cross-reaction. Similar selective binding was observed for enantiomers of secobarbital, thiopental and thiamylal. Assays were developed and used to determine enantiomer pharmacokinetics in rabbits and humans given racemic pentobarbital. In rabbits, difference in clearance of the two isomers was minimal, the result of a slightly larger volume of distribution of the R-enantiomer combined with a slightly higher value of the elimination rate constant beta for the S-enantiomer. In humans, the volume of distribution was 12% greater for the R-enantiomer, but the value of beta was 14% higher for this isomer as well. Thus, the median clearance of the S-enantiomer (1.96 liters/h) was 25% less than that of the R-isomer (2.58 liters/h). The S-enantiomer was also more strongly protein bound in plasma (73.5% vs 63.4% for the R-enantiomer), which is consistent with its structural congruence to S-warfarin, S-phenprocoumon and S-glifumide.

Duke Scholars

Published In

J Pharmacol Exp Ther

ISSN

0022-3565

Publication Date

June 1987

Volume

241

Issue

3

Start / End Page

779 / 785

Location

United States

Related Subject Headings

  • Secobarbital
  • Radioimmunoassay
  • Rabbits
  • Pharmacology & Pharmacy
  • Pentobarbital
  • Kinetics
  • Isomerism
  • Humans
  • Female
  • Blood Proteins
 

Citation

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Cook, C. E., Seltzman, T. B., Tallent, C. R., Lorenzo, B., & Drayer, D. E. (1987). Pharmacokinetics of pentobarbital enantiomers as determined by enantioselective radioimmunoassay after administration of racemate to humans and rabbits. J Pharmacol Exp Ther, 241(3), 779–785.
Cook, C. E., T. B. Seltzman, C. R. Tallent, B. Lorenzo, and D. E. Drayer. “Pharmacokinetics of pentobarbital enantiomers as determined by enantioselective radioimmunoassay after administration of racemate to humans and rabbits.J Pharmacol Exp Ther 241, no. 3 (June 1987): 779–85.
Cook CE, Seltzman TB, Tallent CR, Lorenzo B, Drayer DE. Pharmacokinetics of pentobarbital enantiomers as determined by enantioselective radioimmunoassay after administration of racemate to humans and rabbits. J Pharmacol Exp Ther. 1987 Jun;241(3):779–85.
Cook CE, Seltzman TB, Tallent CR, Lorenzo B, Drayer DE. Pharmacokinetics of pentobarbital enantiomers as determined by enantioselective radioimmunoassay after administration of racemate to humans and rabbits. J Pharmacol Exp Ther. 1987 Jun;241(3):779–785.

Published In

J Pharmacol Exp Ther

ISSN

0022-3565

Publication Date

June 1987

Volume

241

Issue

3

Start / End Page

779 / 785

Location

United States

Related Subject Headings

  • Secobarbital
  • Radioimmunoassay
  • Rabbits
  • Pharmacology & Pharmacy
  • Pentobarbital
  • Kinetics
  • Isomerism
  • Humans
  • Female
  • Blood Proteins