The Elimination of Bupivacaine (Marcain®) after Short Intravenous Infusion in the Dog: with Special Reference to the Role Played by the Liver and Lungs

The elimination of bupivacaine after a short intravenous infusion (1 mg. kg‐1 b.w. for 1 min) was studied in eight dogs. Special interest was focused on the roles played by the liver and lungs. By combining measurements of blood flows and blood concentrations of bupivacaine entering and leaving the liver, it was possible to quantify hepatic elimination of the drug. The concentration time‐curves from pulmonary arterial and aortic blood were similar as regards height and shape and thus did not verify the existence of a pulmonary uptake of bupivacaine of such significance that it dampened the aortic concentration time‐curve. The circulatory changes induced by the infusion were small. The plasma bupivacaine concentration often reached a peak well above 4 μg. ml‐1, but no symptoms of toxicity were registered. The elimination was very fast in comparison with that in man and is probably explained by both a higher hepatic extraction ratio and a greater hepatic blood flow kg‐1 b.w. in the dog. The results support the assumption of a first‐order hepatic hupivacaine elimination. The mean hepatic extraction ratio was constantly about 60% throughout the experiments, and the mean hepatic bupivacaine clearance about 25 ml. kg‐1 min‐1. Cumulative elimination time‐curves were calculated and it was demonstrated that the liver eliminated on average 80% of the given dose during the first hour after the infusion. Finally, it was shown that the mean cumulative elimination time‐curve was not easily linearized, which suggests that the liver eliminated more bupivacaine per time unit during the distribution period than would have been predicted from the usually assumed two or three‐compartment model. It is claimed that distribution volumes calculated by extrapolating the terminal decay slope of the semi‐logarithmic concentration time‐curve to time zero will partly consist of hepatic elimination.