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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Anesthetics, Local, Animals, Dose-Response Relationship, Drug, Drug Interactions, Humans, Hypnotics and Sedatives, In Vitro Techniques, Lidocaine, Male, Microsomes, Liver, Propofol, Rats, Rats, Sprague-Dawley.
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Does propofol inhibit lidocaine metabolism in human and rat liver microsomes? Context: When two drugs are metabolized by similar P450 isoforms, one drug inhibits the metabolism of the other when both the present. The metabolism of lidocaine and propofol can be mediated by similar P450 isoforms. Therefore, we investigated the relationship in the metabolism between lidocaine and propofol in both rat and human liver microsomal P450 (CYP) systems in vitro. (1) Propofol, 4 micro g.ml(-1), as the substrate and lidocaine (between 0.5 and 8 micro g.ml(-1)) and (2) lidocaine, 4.7 micro g.ml(-1), as the substrate and propofol (between 0.5 and 40 micro g.ml(-1)) were reacted separately with human and rat microsomes. The concentrations of lidocaine, its major metabolite (monoethylglycinexylidide, MEGX) and propofol were measured using high-pressure liquid chromatography. The metabolism of lidocaine was presented as a reaction activity (MEGX/lidocaine). The dose-dependent inhibitory effects of propofol on lidocaine metabolism were observed in both the human and rat groups. The IC50 (the concentration producing 50% maximal inhibition) of propofol was 5.0 micro g.ml(-1) and 0.70 micro g.ml(-1) in the human and the rat groups, respectively. The propofol concentration of 5.0 micro g.ml(-1) is within the range of clinical doses for humans. On the other hand, lidocaine did not change propofol metabolism.
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Propofol possesses a dose-dependent inhibitory effect on the metabolism of lidocaine in both human and rat CYP systems in vitro. Final Decision: yes