Effect of a perfluorochemical erythrocyte substitute on the in vitro metabolism of lidocaine using rat liver slices.
Perfluorochemical (PFC) emulsions have recently been investigated for use in the treatment of various clinical conditions requiring red blood cell replacement. The physiological changes which develop following PFC infusion may directly, or indirectly alter the disposition of concomitantly administered agents. This study examined the in vitro metabolism of lidocaine (LC) following pretreatment of rats with a PFC emulsion. Studies were conducted from 2 days to 6 months after initial blood replacement. The control treatment included rats that received a blood exchange with their own blood (SHAM). Analysis of LC and its metabolites was performed using solid phase extraction (SPE) and a modified high performance liquid chromatography (HPLC) method. The predominate metabolite observed in the liver slice preparation was monoethylglycinexylidide (MEGX). No glycinexylidide (GX) was noted in any of the treatments. The results indicate an increase in the in vitro rate of metabolism of LC in rats pretreated with the PFC emulsion. These effects appeared to be time-dependent with maximal increase in metabolism at approximately 5 weeks after the blood exchange and persisting for up to 6 months. These changes in the disappearance of LC in liver slice preparations may reflect PFC-induced enzyme induction and/or altered tissue uptake of LC.
Hoke
J F
JF
Department of Pharmacal Sciences, School of Pharmacy, Auburn University, Alabama 36849.
Ravis
W R
WR
D000818:Animals; D001802:Blood Substitutes / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004338:Drug Combinations; D004912:Erythrocytes / Q000378:metabolism*; D005466:Fluorocarbons / Q000494:pharmacology*; D006895:Hydroxyethyl Starch Derivatives; D007700:Kinetics; D008012:Lidocaine / Q000378:metabolism* / Q000493:pharmacokinetics; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D011919:Rats, Inbred Strains
D001802:Blood Substitutes; D004338:Drug Combinations; D005466:Fluorocarbons; D006895:Hydroxyethyl Starch Derivatives; C017323:glucose, glycerol, hydroxyethyl starch, perfluorodecalin, perfluorotripropylamine, pluronic F-68, salts, yolk phospholipids drug combination; D008012:Lidocaine