Progesterone: does it affect response to drug?
This article presents an overview of the gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex (GBRC) and its in vitro modulation by THP, a metabolite of progesterone, as well as the results of a single-dose study of progesterone and triazolam in 16 post-menopausal women. The study results indicate that a 300 mg oral dose of progesterone administered 2.5 hours prior to a challenge dose of triazolam significantly increases sensitivity to triazolam: concentration values required for 50 percent of maximum effect (EC50) decreased by 20 to 32 percent after pre-treatment with progesterone. These data support the In vitro findings that THP enhances binding of benzodiazepines to the GBRC. The full clinical implications of these data, including extensions to other steroids, need to be explored.
Kroboth
P D
PD
Department of Pharmaceutical Sciences, University of Pittsburgh, School of Pharmacy, PA, USA.
McAuley
J W
JW
D000525:Alprazolam / Q000378:metabolism / Q000494:pharmacology; D003276:Contraceptives, Oral / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008140:Lorazepam / Q000378:metabolism / Q000494:pharmacology; D008875:Middle Aged; D011374:Progesterone / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013693:Temazepam / Q000378:metabolism / Q000494:pharmacology; D014229:Triazolam / Q000378:metabolism / Q000494:pharmacology
D003276:Contraceptives, Oral; D011963:Receptors, GABA-A; D014229:Triazolam; D011374:Progesterone; D013693:Temazepam; D008140:Lorazepam; D000525:Alprazolam