Stereoselective urinary excretion of bupivacaine and its metabolites during epidural infusion

A sensitive and efficient chiral assay for bupivacaine and its three princi pal metabolites desbutylbupivacaine, 4'-hydroxybupivacaine, and 3'-hydroxyb upivacaine has been applied to urine from five male patients receiving post operative epidural infusions of mc-bupivacaine fentanyl over 60-120 hr. The fraction of the dose of bupivacaine (total dose 840-2093 mg) accounted for in urine was 75 +/- 6%. The rate of excretion of bupivacaine enantiomers a pproximated a steady state after similar to 30 hr with values of 1.27 +/- 0 .26 and 0.76 +/- 0.13 mg hr(-1) for (R)- and (S)-enantiomers, respectively. The fraction of the dose of bupivacaine enantiomer excreted unchanged in t he urine (fe) varied from 14.3% to 39.1% for (+)-(R)-bupivacaine and 9.2% t o 14.0% for (-)-(S)-bupivacaine in the five patients. The rate of excretion of all metabolites also reached a steady state after similar to 30 hr and the relative amounts of metabolites excreted into urine (fm) suggest bupiva caine is subject to regioselective and stereoselective clearance, which may vary from patient to patient. Chirality 11:50-55, 1999. (C) 1999 Wiley-Lis s, Inc.