Effects of reduced glutathione and n-acetylcysteine on lidocaine metabolism in cimetidine treated rats.
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 (i.p.) (1 mmol/kg) 1 hour before treatment with cimetidine (0.5 mmol/kg) or saline, and 1 hr later all rats were injected i.p. 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 immuno-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 produce 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.
Testa
R
R
Department of Internal Medicine, University of Genoa, Italy.
Ghia
M
M
Mattioli
F
F
Borzone
S
S
Caglieris
S
S
Mereto
E
E
Giannini
E
E
Risso
D
D
D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D002927:Cimetidine / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D016231:Fluorescence Polarization Immunoassay; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology*; D005978:Glutathione / Q000008:administration & dosage / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008012:Lidocaine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000779:Anesthetics, Local; D016166:Free Radical Scavengers; D006635:Histamine H2 Antagonists; D002927:Cimetidine; D008012:Lidocaine; C001173:monoethylglycinexylidide; D005978:Glutathione; D000111:Acetylcysteine