Lack of influence of cimetidine on bupivacaine levels during parturition

The concurrent use of cimetidine as a prophylactic antacid and bupivacaine as a local anesthetic for epidural anesthesia for cesarean section has been promoted. However, cimetidine is known to inhibit clearance of many drugs by reducing hepatic blood flow and by inhibiting cytochrome P-450 enzymes. The purpose of this study was to determine whether cimetidine during epidural anesthesia alters the metabolism, disposition, protein binding, or placental transfer of bupivacaine. Thirty-six patients undergoing cesarean section with 0.5% bupivacaine for epidural anesthesia were studied. Sixteen patients received cimetidine (300 mg IM) 1-4 hr before cesarean section and 20 control patients received sodium citrate (30 ml PO) 10 min preoperatively. Bupivacaine and its inactive metabolite, 2,6-pipecolylxylidine (PPX) were quantitated by gas chromatography/mass spectrometry. Maternal plasma concentration time curves, fetal/maternal ratios at delivery, cord vein/cord artery ratios. PPX/bupivacaine ratios, and maternal and neonatal urinary excretion were compared between the two groups. No significant differences could be found between the groups in any of the outcome variables. However, in the presence of cimetidine, the percentage of unbound bupivacaine significantly increased from 1.36 +/- 0.63 to 1.66 +/- 0.78%. The results suggest that a single 300-mg IM dose of cimetidine does not significantly affect bupivacaine disposition or metabolism in parturients when given 1-4 hr before anesthesia.