EXTRADURAL ADMINISTRATION OF BUPIVACAINE: PHARMACOKINETICS AND METABOLISM IN PREGNANT AND NON-PREGNANT WOMEN

We found a similar time (about 0.4 h) to maximum serum concentrationafter extradural administration of bupivacaine 1.78 (SD 0.27)mg kg^–1 to six pregnant patients at term, 1.58 (0.13)mg kg^–1 to six women younger than 65 yr and 1.50 mg kg^–1to six women older than 65 yr. There were no significant differencesin terminal half-life. No unconjugated 4'-hydroxy-bupivacainewas detected in the serum and urine of pregnant patients, incontrast with the other groups. The pregnant patients had significantlygreater serum concentrations of the N-dealkylated metabolite,N-desbutyl-bupivacaine (DBB), than the non-pregnant groups.In contrast with 4'-hydroxy-bupivacaine, no conjugated formsof bupivacaine and desbutyl-bupivacaine were detected in urine.The mean total urinary excretion of bupivacaine and its metabolitesand their conjugates varied between 2.46 and 3.22% of the totaldose administered in the three patient groups, indicating thatboth 4'-hydroxylation and N-dealkylation are minor metabolicpathways in man.