CARDIOVASCULAR EFFECTS AND REGIONAL CLEARANCES OF I.V. BUPIVACAINE IN SHEEP: ENANTIOMERIC ANALYSIS

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Abstract
All currently available aminoacylaniline local anaesthetics, except lignocaine, contain a chiral centre but are used as racemates, a fact usually ignored in pharmacokinetic studies. This study reports the cardiovascular effects, and the regional and total body clearances of the enantio-mers of bupivacaine determined at two steady state periods (3–4 h and 23–24 h) during continuous i.v. infusion to subtoxic concentrations in conscious sheep. Racemic (RS)-bupivacaine hydrochloride 1 mg min, was infused in five sheep that had been prepared at least 1 week previously with appropriate intravascular can-nulae. The infusion of Fts-bupivacaine produced constant arterial R( +)- and s(−)-bupivacaine concentrations of 0.20–0.68 mg litre1 and 0.22–0.94 mg litre1, respectively. This caused no appreciable cardiovascular effects. The hepatic clearance of R( +)- was greater than that of S−)-bupivacaine (P < 0.05) with mean (so) clearance at the two respective time periods being 1.37 (0.78) and 1.47 (0.57) litre minand 1.01 (0.72) and 1.29 (0.47) litre min−1. There was no significant clearance of either enantiomer by the lungs, brain, heart, gut, kidneys or hindquarters. It was concluded that, although the clearances of the enantiomers differed, the total body clearance of both enantiomers was accounted for by hepatic clearance exclusively. There was no evidence of time dependent kinetics.

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