Effect of Gastrointestinal Maturation on Absorption of β‐lactam Antibiotics

Gastrointestinal absorption of cefazolin, which is poorly absorbed in adults, and of cephradine, which is well absorbed in adults, was studied in rats during their development. Significantly higher concentrations of cefazolin in plasma after oral administration were observed in 1- and 2-week-old rats compared with 3-week-old and adult rats. A marked difference in the absorption of cefazolin by 2- and 3-week-old rats (at weaning period) was observed. No such marked difference in the absorption of cephradine by rats of various age groups was found. With cefazolin, a similar pattern of developmental change in jejunal uptake was observed. Cortisone, which causes early maturation of the intestinal membrane, was given as a preweaning injection to 2-week-old rats. This treatment decreased concentrations of cefazolin in plasma and jejunal uptake of cefazolin. Thus, the absorption of cefazolin in 1- and 2-week-old rats seems to depend on the permeability of the immature intestinal membrane before weaning. Cephradine absorption from the intestine of 1-week-old rats became saturated and inhibited by carnosine and glycylglycine when studied by the in situ loop method. Cefazolin absorption was proportional to luminally administered doses and was not affected by carnosine and glycylglycine. A nonsaturable process for cefazolin and a saturable process for cephradine were also observed in an in vitro uptake experiment.