Stereoselective urinary excretion of bupivacaine and its metabolites during epidural infusion.

A sensitive and efficient chiral assay for bupivacaine and its three principal metabolites desbutylbupivacaine, 4'-hydroxybupivacaine, and 3'-hydroxybupivacaine has been applied to urine from five male patients receiving postoperative epidural infusions of rac-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' approximated a steady state after approximately 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 the urine (fe) varied from 14.3% to 39.1% for (+)-(R)-bupivacaine and 9.2% to 14.0% for (-)-(S)-bupivacaine in the five patients. The rate of excretion of all metabolites also reached a steady state after approximately 30 hr and the relative amounts of metabolites excreted into urine (fm) suggest bupivacaine is subject to regioselective and stereoselective clearance, which may vary from patient to patient.