Differential effects of various antiinflammatory drugs on theophylline neurotoxicity

Amnon Hoffman*, Mishel Afargan, Evelyne Pinto, Dalia Gilhar, Joshua Backon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The purpose of the present investigation was to evaluate whether antiinflammatory drugs affect the pharmacodynamics of theophylline-induced seizures. Adult male Lewis rats were treated with either dexamethasone (DEX), hydrocortisone (HYD), ibuprofen (IBU), or mefenamic acid (MFA), for 4 consecutive days. On the fourth day they received a constant infusion of theophylline (2 mg/min IV) until the onset of maximal seizures. Then, blood and cerebrospinal fluid (CSF) were obtained for theophylline concentration determinations by HPLC. It was found that pretreatment with the corticosteroids DEX and HYD elevated the CSF theophylline concentration required to induce maximal seizures in comparison to the untreated rats (242 ± 6, 232 ± 6, and 203 ± 10 mg/l, respectively, n = 10, p < 5). MFA also increased the CSF theophylline concentration at the end-point in comparison to the controls (p < 0.01), whereas pretreatment with IBU had no effect (280 ± 10 MFA, 225 ± 9 IBU vs. 220 ± 8 controls, n = 12). The data suggests that concomitant treatment with antiinflamatory drugs, together with theophylline, do not increase the risk for theophylline-induced seizures. Moreover, in certain cases they may elevate the seizure threshold and protect against these hazardous episodes.

Original languageAmerican English
Pages (from-to)335-339
Number of pages5
JournalPharmacology Biochemistry and Behavior
Volume49
Issue number2
DOIs
StatePublished - Oct 1994

Keywords

  • Antiinflammatory
  • Dexamethasone
  • Drug interaction
  • Hydrocortisone
  • Ibufrofen
  • Induced seizures
  • Mefenamic acid
  • NSAID
  • Neurotoxicity
  • Pharmacodynamics
  • Steroids
  • Theophylline

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