Studies on absorption promoters for rectal delivery preparations. I. Promoting efficacy of enamine derivatives of amino acids for the rectal absorption of beta-lactam antibiotics in rabbits
Murakami, T.; Yata, N.; Tamauchi, H.; Nakai, J.; Yamazaki, M.; Kamada, A.
Chemical and Pharmaceutical Bulletin 29(7): 1998-2004
ISSN/ISBN: 0009-2363 PMID: 6796279 DOI: 10.1248/cpb.29.1998
Enamine derivatives of amino acids were synthesized and their promoting efficacies for the rectal absorption of .beta.-lactam antibiotics were studied in rabbits. Ethyl acetoacetate (EtAA) enamine derivatives were preferentially studied because of the low toxicity of EtAA generated by the hydrolysis of the enamine moiety in the rectum and blood stream. The EtAA enamine of sodium D-phenylglycine (PG EtAA Na) had remarkable promoting efficacy for the rectal absorption of sodium ampicillin, cephalothin, cephapirin, cefazolin and cephaloridine. Other enamine derivatives of amino acids also showed promoting efficacy for the rectal absorption of penicillins and cephalosporins which could not permeate alone due to their poor lipid affinity. The promoting efficacy of PG EtAA Na for the rectal absorption of antibiotics increased with decrease in the partition coefficients. The present results suggest that the enamine derivatives of amino acids are clinically applicable for use in rectal delivery preparations of penicillins and cephalosporins which cannot permeate unaided through the rectal membrane.