Stereospecificity of the Enzymatic Biotransformation of the Enantiomers of Prilocaine (Citanest®)

No differences have been found between D‐(—)‐, L‐(+)‐ and DL‐(±)‐prilocaine (citanest®) with regard to intravenous LD50's in mice, nor have any differences been found between the D‐(—)‐ and L‐(+)‐forms on subcutaneous injection. Compared to L‐(+)‐prilocaine, D‐(—)‐prilocaine was less toxic on intravenous infusion (mice, 0.12–0.30 mg/min.) and had less cumulative effect in rabbits (20 mg/kg each 15 min.). The plasma concentrations (cats) of the D‐(—)‐form (25 mg/kg intravenously) were lower than those of the L‐(+)‐form and more o‐toluidine, one of the metabolites of prilocaine, was detected in the blood. D‐(—)‐prilocaine also produced methaemoglobinaemia at a more rapid rate. The 14C‐labelled enantiomers of prilocaine were hydrolyzed at significantly different rates by liver homogenates, slices (mice, rabbits, cats) and isolated microsomes (rabbits); D‐(—)‐prilocaine had the highest affinity for the enzyme(s). Thus, a significant stereospecificity of the hydrolyzing enzymes in their reaction with the enantiomers of prilocaine was found. However, no evidence was obtained which could suggest substitution of the local anaesthetic prilocaine by either of its optical isomers.