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

Abstract

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, Km = 15.80 +/- 2.92 mM, P*m = 0, J*c = 0.75 +/- 0.04 for ampicillin; J*max = 0.044 +/- 0.018 mM, Km = 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, Km = 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.