Characterization of the oral absorption of several aminopenicillins: Determination of intrinsic membrane absorption parameters in the rat intestine in situ

The absorption mechanism of several penicillins was characterized using in situ single-pass intestinal perfusion in the rat. The intrinsic membrane absorption parameters were determined using a modified boundary layer model (fitted value ± S.E.): J ∗ max = 11.78 ± 1.88 mM, K m = 15.80 ± 2.92 mM, P ∗ m = 0, J ∗ c = 0.75 ± 0.04 for ampicillin; J ∗ max = 0.044 ± 0.018 mM, K m = 0.058 ± 0.026 mM , P ∗ m = 0.558 ± 0.051, P ∗ c = 0.757 ± 0.088 for amoxicillin; and J ∗ max = 16.30 ± 3.40 mM, K m = 14.00 ± 3.30 mM, P ∗ m = 0 , P ∗ c = 1.14 ± 0.05 for cyclacillin. All of the aminopenicillins studied demonstrated saturable absorption kinetics as indicated by their concentration-dependent wall permeabilities. Inhibition studies were performed to confirm the existence of a nonpassive absorption mechanism. The intrinsic wall permeability ( P ∗ w ) of 0.01 mM ampicillin was significantly lowered by 1 mM amoxicillin and the P ∗ w of 0.01 mM amoxicillin was reduced by 2 mM cephradine consistent with competitive inhibition.