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 parameters were determined using a modified boundary layer model (fitted value +/- S.E.):  Jmax* = 11.78 +/- 1.88 mM, Km = 15.80 +/- 2.92 mM, Pm* = 0, Pc* = 0.75 +/- 0.04 for ampicillin; Jmax* = 0.044 +/- 0.018 mM, Km = 0.058 +/- 0.026 mM, Pm* = 0.558 +/- 0.051, Pc* = 0.757 +/- 0.088 for amoxicillin; and Jmax* = 16.30 +/- 3.40 mM, Km = 14.00 +/- 3.30 mM, Pm* = 0, Pc* = 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 (Pw*) of 0.01 mM ampicillin was significantly lowered by 1 mM amoxicillin and the Pw* of 0.01 mM amoxicillin was reduced by 2 mM cephradine consistent with competitive inhibition.
Oh D-M
College of Pharmacy, The University of Michigan, Ann Arbor 48109-1065.
Sinko
P J
PJ
Amidon
G L
GL
D000042:Absorption / Q000187:drug effects; D000658:Amoxicillin / Q000493:pharmacokinetics*; D000667:Ampicillin / Q000493:pharmacokinetics*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003493:Cyclacillin / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects*; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D010539:Permeability; D051381:Rats
D003493:Cyclacillin; D000667:Ampicillin; D000658:Amoxicillin