The recognized increase in cardiotoxicity of one bupivacaine isomer led to the stereospecific production of ropivacaine as the single "S" (—) enantiomer. Ropivacaine is the propyl analog of mepivacaine (methyl) and bupivacaine (butyl). The pKa of the tertiary nitrogen is 8.1, and it displays the same degree of protein binding as bupivacaine (—94%). Although ropivacaine has similar properties as bupivacaine, it displays less cardiotoxicity. The shortened alkyl chain gives it approximately one third of the lipid solubility of bupivacaine. Animal studies have shown that ropivacaine dissociates from cardiac sodium channels more rapidly than bupivacaine. This decreases the sodium channel block in the heart and may be responsible for the reduced cardiotoxicity of ropivacaine.92
Ropivacaine undergoes extensive metabolism in humans with only 1% of a dose excreted unchanged in the urine.96 Four metabolites of ropivacaine have been identified from human liver microsome incubations and in vivo studies. The CYP1A2 isoform was found to be responsible for the formation of 3-OH ropivacaine, the primary ropivacaine metabolite. The CYP3A4 isoform was responsible for the formation of 4-OH ropivacaine, 2-OH methyl-ropivacaine, and the N-dealkylated metabolite (S)-2',6'-pipecoloxyli-dide.97 Coadministered inhibitors of CYP1A2 may be of clinical importance, CYP3A4 inhibitors seem to be of less clinical relevance.98
Ropivacaine is a long-acting amide-type local anesthetic with inherent vasoconstrictor activities, so it does not require the use of additional vasoconstrictors. It is approved for epidural, nerve block, infiltration, and intrathecal anesthesia.
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