DISPOSITION OF MEPIVACAINE AND BUPIVACAINE ENANTIOMERS IN SHEEP

• Published in: British journal of anaesthesia : BJA Vol. 67; no. 3; pp. 239 - 246
• Main Author: MATHER, L.E.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.09.1991; Oxford University Press
• Subjects: Anaesthetics; Anesthetics. Neuromuscular blocking agents; Animals; Biological and medical sciences; Biotransform-ation: stereoisomers; bupivacaine; Bupivacaine - administration & dosage; Bupivacaine - pharmacokinetics; Cardiac Output; Female; Half-Life; Heart Atria; Injections; Liver - metabolism; local: mepivacaine; Medical sciences; Mepivacaine - administration & dosage; Mepivacaine - pharmacokinetics; Metabolic Clearance Rate; Neuropharmacology; Pharmacokinetics: extraction ratio; Pharmacology. Drug treatments; Sheep; Stereoisomerism; local: mepivacaine; Biotransform-ation: stereoisomers; Pharmacokinetics: extraction ratio; bupivacaine; Anaesthetics; Local anesthetic; Stereoselectivity; Vertebrata; Mammalia; Intravenous administration; Animal; Enantiomer; Sheep; Artiodactyla; Pharmacokinetics; Ungulata
• ISSN: 0007-0912; 1471-6771
• DOI: 10.1093/bja/67.3.239

Mepivacaine and bupivacaine are used clinically as racemic mixtures of enantiomers. In these studies the enantiomers of each agent were administered separately to sheep by i.v. bolus injection on separate occasions. Enantioselective disposition was deemed if the R:s ratio of the relevant pharmacokinetic parameter differed significantly from unity. Both enantiomers of both agents were cleared principally by the liver; urinary excretion of unmetabolized agents accounted for < 2% of the doses. For R(−)- and S(+)-mepivacaine. respective mean (SEM) values of parameters were: total body clearance 1.20 (0.29) litre min−1 and 0.97 (0.20) litre min−1 (ns); total volume of distribution 144 (39) litre and 80 (21) litre (P < 0.05); slow half-life 120 (40) min and 84 (22) min (ns); mean hepatic extraction ratio 0.50 (0.14) and 0.52 (0.09) (ns); mean hepatic clearance 0.75 (0.23) litre min1 and 0.75 (0.18) litre min1 (ns). For R(+)- and s(−)-bupivacaine, respective values were: total body clearance 0.77 (0.33) litre m nd 0.53 (0.26) litre min (P<0.05); total volume of distribution 40 (10) litre and 43 (10) litre (ns); slow half-life 57 (10) min and 104 (21) min (P<0.05); mean hepatic extraction ratio 0.46 (0.15) and 0.29 (0.13) (P < 0.05); mean hepatic clearance 0.85 (0.31) litre min and 0.54 (0.26) litre min (P < 0.05). Thus there was enantioselective distribution of mepivacaine and enantioselective clearance of bupivacaine, but the magnitude of the effect was relatively small.