Lidocaine increases lung uptake of propranolol

Abstract

Intravenous administration of 2 or more drugs that accumulate in the lung may result in interaction and altered pharmacokinetics. Lidocaine enhances propranolol uptake in rat lungs in vitro. Since coadministration of both drugs is common in clinical practice, we investigated their possible interaction in vivo. Single-pass lung uptake of propranolol was measured with a double indicator dilution technique. In part I (5 dogs), a mixture of propranolol and indocyanine green was injected as a bolus into the right atrium, and a single sample of the aortic outflow blood collected. Propranolol uptake was 54% before, and 81% during lidocaine infusion (P ≤ 0.01). This corresponded to a fall in the mean aortic outflow concentration of the beta adrenoceptor antagonist from 158 ± 46µg/l to 97 ± 35µg/ml (P ≤ 0.01). There was no change in the aortic concentration of lidocaine immediately after injection of propranolol, which suggests little or no displacement of lidocaine from the lungs. To study the shape and time course of the indicator outflow curves in detail, consecutive 1-s samples of aortic blood were collected after similar injections in 3 dogs (part II). This showed that propranolol outflow curves were flatter and more delayed in the presence of lidocaine. Although the calculated propranolol uptake values were lower than in part I, a substantial increase in uptake during lidocaine infusion was confirmed. Thus, interaction between propranolol and lidocaine may alter the pharmacokinetics of the injected beta adrenoceptor antagonist. Drug interaction in the lungs may be an important, but neglected, consideration in therapeutics.