Cardiovascular effects and regional clearances of i.v. bupivacaine in sheep: enantiomeric analysis.

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 enantiomers 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-1, was infused in five sheep that had been prepared at least 1 week previously with appropriate intravascular cannulae. The infusion of RS-bupivacaine produced constant arterial R(+)- and s(-)-bupivacaine concentrations of 0.20-0.68 mg litre-1 and 0.22-0.94 mg litre-1, respectively. This caused no appreciable cardiovascular effects. The hepatic clearance of R(+)- was greater than that of S(-)-bupivacaine (P less than 0.05) with mean (SD) clearance at the two respective time periods being 1.37 (0.78) and 1.47 (0.57) litre min-1 and 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.

journal_name

Br J Anaesth

authors

Rutten AJ,Mather LE,McLean CF

doi

10.1093/bja/67.3.247

subject

Has Abstract

pub_date

1991-09-01 00:00:00

pages

247-56

issue

3

eissn

0007-0912

issn

1471-6771

pii

S0007-0912(17)47961-X

journal_volume

67

pub_type

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