Plasma Concentrations of the Stereoisomers of Prilocaine After Administration of the Racemate: Implications for Toxicity? †

Abstract

A chiral high pressure liquid chromatography method was developed to measure the separate isomers of prilocaine in plasma after administration of the racemate. The concentrations of the isomers in six patients were similar (S(+)/R(-) = 1.06 (SD 0.06)) after brachial plexus block with 1.5% (RS)-prilocaine hydrochloride 35 ml, suggesting that a higher systemic safety margin may not be achieved by substituting racemic prilocaine by one of its isomers. Much higher plasma concentrations of the S(+)- than the R(-)-form after oral administration of 300 mg of the racemate (n = 4) indicated a large difference in intrinsic metabolic clearance of the isomers on first pass through gut, liver or both organs.

Development and validation of gas chromatography–mass spectroscopy method for determination of prilocaine HCl in human plasma using internal standard methodology

“…These reports have led to a renewed interest for determination of local anesthetics. Although the local anesthetic prilocaine is less cardio-and neurotoxic than lidocaine, it bears the disadvantage of the formation of methemoglobin by the metabolite o-toluidine (Warren et al, 1974;Tucker et al, 1990;Rudolf et al, 1995). Thus, sensitive and specific analytical methods are needed for determination of prilocaine in plasma after local injections.…”

“…Several analytical methods for analysis of prilocaine in biological samples have been reported. A chiral pressure liquid chromatography method for measure of the separate isomers of prilocaine in plasma after administration of the racemate (Tucker et al, 1990) and for the quantitation of R(−) and S(+) prilocaine in human serum (Siluvera and Stewart, 1996) has been reported.…”

When Regional Anesthesia Met Pharmacokinetics

“…In the early 1970s, we were interested in investigating the enantioselective pharmacokinetics of the agents used as racemates, but the analytical technology at the time was incapable of separating stereoisomers; this technology would only become available in the late 1980s. 25,26 In the 1990s, some pharmaceutical companies perceived the advantages of introducing appropriate enantiopure alternatives. 27 Among local anesthetic agents, ropivacaine, the enantiopure propyl homolog of S-bupivacaine, was launched at the 11th World Congress of Anaesthesiologists meeting held in Sydney, Australia, in 1996, and levobupivacaine, the S-enantiomer of bupivacaine, was launched at the European Society of Regional Anaesthesia meeting held in Gothenburg, Sweden in 2001.…”

Stereoselective activity of local anesthetics

“…Tuckeret al [43] compared the plasma concentrations of S-(+)-and R-(-)-prilocaine after both perineural injection (brachial plexus block) and after oral administration. No significant differences in plasma concentration were found after perineural injection; however, following oral administration of racemic prilocaine, very low plasma concentrations of the R-(-)-enantiomer were seen.…”