Gender Differences in the Pharmacodynamics of Barbiturates in Rats

Amnon Hoffman*, Gerhard Levy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

There is considerable evidence of gender differences in the pharmacokinetics of numerous drugs, particularly in rodents, but very limited information concerning the effect of gender on pharmacodynamic characteristics (concentration-activity relationships). In this study, heptabarbital or phenobarbital was administered to male and female rats and the concentrations of these drugs in the brain, cerebrospinal fluid and serum at onset or offset of loss of righting reflex were determined. For heptabarbital, offset concentrations were determined in Lewis rats and onset concentrations in Wistar rats. Onset concentrations of phenobarbital were determined in Wistar rats. In all cases, the barbiturate concentrations in males were significantly lower than those in females at the pharmacologic endpoint. The biologic (serum) half-life of heptabarbital is much shorter in males (∼10 min) than in females (∼90 min) and this pharmacokinetic difference is reflected by the considerably longer duration of effect of the drug in females.

Original languageAmerican English
Pages (from-to)976-981
Number of pages6
JournalPharmaceutical Research
Volume6
Issue number11
DOIs
StatePublished - Nov 1989
Externally publishedYes

Keywords

  • concentration-effect relationship
  • gender difference
  • heptabarbital
  • phenobarbital
  • sleeping time

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