Endotoxic shock alters the pharmacokinetics of lidocaine and monoethylglycinexylidide

Shock
David S McKindleyClinton Chichester

Abstract

Significant hepatic dysfunction occurs following endotoxin administration. Although the metabolism of lidocaine to one of the primary metabolites of lidocaine, monoethylglycinexylidide (MEGX), has been used as a marker of hepatic function under various conditions, it remains unknown whether these compounds can be used in vivo to evaluate hepatic function in a rat model of endotoxic shock. To study this, cytochrome P450-3A4 (CYP3A4) was determined after harvesting hepatic microsomes, hepatic blood flow was determined using radioactive microspheres, and the pharmacokinetics of lidocaine and MEGX were evaluated. Adult male Sprague-Dawley rats were divided into endotoxin (45 mg/kg, intraperitoneally; n = 28) or control (n = 32) groups. The CYP3A4 was significantly reduced after endotoxic shock. Carboxylesterase (hydrolase S) content, which was used as a control for microsomal protein, was not significantly different between groups. Total hepatic blood flow was significantly decreased (36.2 +/- 8.4 mL/min/100 g tissue vs. 120.4 +/- 10.6 mL/min/100 g tissue), which was due to the decreased portal blood flow. For the lidocaine and MEGX experiment, lidocaine (2 mg/kg) was administered followed by serial blood samples collected up to 2 ...Continue Reading

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Citations

Nov 30, 2004·European Journal of Clinical Pharmacology·Tal Brosh-NissimovReuven Porat
Nov 12, 2003·Forensic Science International : Synergy·Fumio Moriya, Yoshiaki Hashimoto
Feb 2, 2016·Journal of the American Veterinary Medical Association·Luca Bellini, Christopher J Seymour

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