The intravenous toxicity and clearance of bupivacaine in man

Systemic toxicity of bupivacaine is lower in man than might be predicted from acute toxicity studies in animals due to its shorter duration of action and lower plasma levels during prolonged analgesia.

Abstract

Bupivacaine hydrochloride has been administered to volunteers at a dose of 1.35 mg. per kilogram by intravenous infusion. No significant changes in blood pressure, electrocardiogram, or heart rate were observed. Subjective signs of toxicity were mild. Plasma levels were determined for 8 hours following injection and these indicated that, after an initial phaw of rapid changes in plasma levels due to distribution, bupivacaine has a half‐life of approximately 21,2 hours. The highest plasma level recorded was 22.5 Pg per milliliter in arterial blood. Less than 10 per cent of the dose administered was excreted unchanged in the urine and urinary excretion was complete within 24 hours. The maior route of clearance is through metabolism. Bupivacaine is more than 90 per cent bound to plasma proteins at concentrations of 1 Pg per milliliter. Hence systemic toxicity of bupivacaine is lower in man than might be predicted from acute toxicity studies in animals. The rate of clearance of bupivacaine is approximately the same as lignocaine and mepivacaine but it has a much longer duration of action. Consequently plasma levels of bupivacaine do not rise to the same extent as with lignocaine or mepivacaine during prolonged analgesia.