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Influence of stress and dexamethasone on plasma levels of antiepileptic drugs and theophylline in rats

Year: 2025
Type: article
Abstract: Elevation of plasma glucocorticoids (GCs) during stress and GCs treatment in different diseases can modify the liver enzymes activity, biotransformation and the effectiveness simultaneously used medications. Recently the effect of GCs, especially of dexamethasone (DEX) – a synthetic GCs receptor agonist on cytochrome P450 enzymes was described. The aim of the present study was to investigate whether the pharmacokinetc of the selected antiepileptic drugs: phenytoin (PHT), vaproate magnesium (VPL), phenobarbital (PB) or theophylline (THEO) could be modified in the rats subjected to acute or chronic stress, and in those treated with DEX, too. All drugs were injected at a single dose 48 h or 1 h after the last stress session of the chronic unpredictable stress (a variant of Katz et al.). Acute stress was an electric footshock. 1 h later all drugs were injected. Additionally, an experiment was conducted on the rats that were first treated with DEX at a single dose and then 3 h later with all drugs. The control group of animals was treated with drugs alone. 30 (VLP and THEO), 60 (PB) or 120 min (PHT) later, the blood of rats was taken to estimate the level of drugs by immunofluorescence. In the rats subjected to chronic and acute stress and also after DEX treated a decrease of the free plasma levels of PHT and VPL was observed. The total plasma level of THEO was significantly decreased in rats with only acute stress or treated with DEX. However, the free plasma level of PB was significantly increased in rats injected with DEX. These date obviously indicate that each kind of stress as well as GCs (e.g. DEX) may change the metabolism of drugs and it should be taken into consideration during pharmacotherapy.
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $84
OpenAlex ID: W7167444785
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