Effects of reduced glutathione and n-acetylcysteine on lidocaine metabolism in cimetidine treated rats

R. Testa, M. Ghia, F. Mattioli, S. Borzone, S. Caglieris, E. Mereto, E. Giannini, D. Risso

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Abstract

The aim of this work was to evaluate the effects of exogenous glutathione (GSH) and N-acetylcysteine (NAC) on the formation of monoethylglycinexylidide (MEGX) from lidocaine in rats with and without the administration of cimetidine. GSH and NAC were administered intraperitoneally (ip) (1 mmol/kg) 1 hour before treatment with cimetidine (0.5 mmol/kg) or saline, and 1 hr later all rats were injected ip with lidocaine (1 mg/kg). Blood samples were drawn 30 min after the lidocaine injection. MEGX and lidocaine serum concentrations were determined by means of fluorescence polarization immune-assay using the TDX system. Cimetidine produced a decrease in MEGX levels (from 210 ± 18 to 164 ± 13 ng/mL) and a parallel increase in lidocaine levels (from 73 ± 22 to 172 ± 47 ng/mL), consistent with cytochrome P-450 3A inhibition. Both GSH and NAC produced a significant decrease in MEGX levels (151 ± 16 and 139 ± 14 ng/mL, respectively), but no significant increase in lidocaine levels were found. As compared to the cimetidine group, pre-treatment using either GSH or NAC with cimetidine produced a marked decrease in lidocaine levels (37 ± 27 and 63 ± 28 ng/mL, respectively) and no modification of MEGX levels (155 ± 12 and 165 ± 22 ng/mL, respectively). These results suggest that GSH and NAC might accelerate the lidocaine metabolism while counteracting the inhibitory effect of cimetidine.

Original languageEnglish
Pages (from-to)220-224
Number of pages5
JournalFundamental and Clinical Pharmacology
Volume12
Issue number2
Publication statusPublished - 1998

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Keywords

  • Cimetidine
  • Glutathione
  • Lidocaine
  • MEGX
  • N-acetylcysteine
  • Rats

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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