A study of the in vitro clinical interaction between lidocaine and premedications using rat liver microsomes

Abstract

<jats:p> In this study, we have investigated the relationship between lidocaine metabolism and premedication, i.e., psychotropic and anti-anxiety agents (diazepam, midazolam), hypnotics (pentobarbital, thiamylal), depolarizing muscular relaxants (vecuronium, pancuronium and suxamethonium), an active anti-hypertensive (clonidine) and an H<jats:sub>2</jats:sub> receptor antagonist (cimetidine) using rat hepatic microsomes in vitro. Lidocaine metabolism was noncompetitively inhibited by midazolam (K<jats:sub>i</jats:sub>=29.0 mM). Thilamylal was a moderate competitive inhibitor of lidocaine metabolism (K<jats:sub>i</jats:sub>=77.8 mM). Pentobarbital, diazepam and cimetidine weakly inhibited lidocaine metabolism formation in a concentration-dependent manner at high substrate concentrations. On the other hand, vecuronium, pancuronium, suxamethonium and clonidine did not inhibit lidocaine metabolism over the therapeutic range. These results show that the interaction between lidocaine and midazolam and thiamylal, catalyzed by a similar cytochrome P450, is of potential importance in toxicological and clinical studies. </jats:p>

Free lidocaine concentrations during continuous epidural anesthesia in geriatric patients

“…8,9 Diazepam weakly inhibited lidocaine metabolism at a high concentration in an in vitro study, 23 however, it was reported that 10 mg diazepam administration did not influence the plasma concentrations of lidocaine after a caudal block in children. 24 In the present study, the administered doses of diazepam were 1.4 Ϯ 1.0 mg in the eldely group and 8.6 Ϯ 2.4 mg in the middleaged group, respectively.…”

?Alternative? effects of local anesthetic agents

“…In-vitro-Studien konnten zeigen, dass Lokalanästheti-ka die Thrombozytenaggregation via Blockade des Ca ++ -Einstroms oder durch Mobilisation intrazellulärer Ca ++ -Speicher inhibieren [21]. Bupivacain verlän-gert in vitro die "Activated Clotting Time" (ACT) und verschiedene Parameter des Thrombelastogramms (TEG) [47].Die antithrombotische Aktivität von Lidocain konnte Stewart zudem im Kaninchenmodell zeigen [87] [68]. Der Abbau von Lidocain wurde hierbei nichtkompetitiv von Midazolam und kompetitiv von Thiamylal gehemmt.…”