Opioid effects on lidocaine disposition and toxicity in mice

Morphine sulfate, 20 mg/kg, or equivalent doses of the opioids, meperidine and fentanyl, elevated plasma levels of lidocaine after i.v. administration of this antiarrhythmic drug. Plasma levels of the lidocaine metabolites, monoethylglycinexylidine and glycinexylidine, were reduced by opioids as lidocaine levels were elevated. The opioid antagonist, naloxone, 1 mg/kg, reversed the effects of morphine, 20 mg/kg, on lidocaine. After morphine, plasma levels of both lidocaine and indocyanine green were elevated, suggesting that the effect of morphine on lidocaine disposition was related to reduced hepatic blood flow. Morphine and meperidine increased lethality of i.v. lidocaine, as shown by marked reduction of LD50 by either opioid.