Distribution, Biotransformation and Excretion of Bupivacaine in the Rat and the Monkey

Abstract

1. Following subcutaneous administration of [pipecolyl-G-³H]bupivacaine, radioactivity was slowly absorbed from the injection site; the absorbed radioactivity was distributed rapidly in all tissues examined.

2. Tissue levels peaked between 0·25 and 1 h, but by 24 h were very low.

3. The monkey excreted 80% of the radioactivity in the urine; in the rat only 50% was excreted by this route and the remainder in the bile.

4. The major metabolite in rat urine was a conjugate of 1-butyl-3′-hydroxy-pipecolo-2′,6′-xylidide. Debutylated bupivacaine was not found in rat urine.

5. In the monkey, the amide hydrolysis product, pipecolic acid, was the major metabolite.

6. Debutylation and hydroxylation of bupivacaine also occurred in the monkey; however, only the 4′-hydroxy metabolite was detected.