Amoxicillin intestinal absorption

Westfrfial JF, Jehl F, Bn aid JM, Carbcm C Amoxicillin intestinal absorptic reduction by amiloride possible role of the Na(+)-H(+) exchanger. Clin Pharmactd Ther (1995) 57, 257-64. 

Barr, W.H., et al. 1994. Different absorption of amoxicillin from the human small and large intestine. Clin Pharmacol Ther 56 279. 

Absorption Most of the penicillins are incompletely absorbed after oral administration and reach the intestine in sufficient amounts to affect the composition of the intestinal flora. However, amoxicillin is almost completely absorbed. Consequently, it is not appropriate therapy for the treatment of shigella- or salmonella-derived enteritis, since therapeutically effective levels do not reach the organisms in the intestinal crypts. Absorption of penicillin G and all the penicillinase-resistant penicillins is decreased by food in the stomach since gastric emptying time is reduced and the drugs are destroyed in the acidic environment. Therefore, they must be administered 30-60 minutes before meals or 2-3 hours postprandially. Other penicillins are less affected by food. 

An active dipeptide transport system that depends on hydrogen ions takes up non-ester amino-beta-lactams (penicillin, amoxicillin, and oral first-generation cephalosporins) (337-339) and specific cephalosporins that lack the alpha-amino group (cefixime, ceftibuten, cefdinir, cef-prozil) (340,341). Nifedipine increases amoxiciUin and cefixime absorption, probably by stimulating the dipeptide transport system, since the serum concentrations of passively absorbed drugs and intestinal blood flow did not change (342-344). 

Amoxaclllln (Table 38.5). Amoxicillin is a close analogue of ampicillin, in which a para-phenolic hydroxyl group has been introduced into the side-chain phenyl moiety. This adjusts the isoelectric point of the drug to a more acidic value, and this is believed to be partially responsible, along with the intestine peptide transporter, for the enhanced blood levels obtained with amoxicillin as compared to ampicillin itself (Table 38.6). Better oral absorption (74-92%) leads to less disturbance of the normal Gl flora and, therefore, less drug-induced diarrhea. The antimicrobial spectrum and clinical uses of amoxicillin are approximately the same as those of ampicillin itself, and it is presently one of the most popular drugs in North America. 

Although the absorption of most drugs can be explained by passive diffusion, some compounds have specific transport mechanisms. An example is the absorption in the intestine of some penicillin derivatives, e.g. cyclacillin (1 aminocyclohexylpenicillin). This process is saturable, proceeds against an unfavourable concentration gradient and shows temperature dependence. Transport of amoxicillin is also carrier mediated but it is not an active process. Since these materials are xenobiotics, the transport mechanism is probably one which serves some other function in the body. The two penicillins probably share the same carrier since they are mutually competitive. Digitalis and other cardioselective glycosides also demonstrate behaviour not compatible with simple partition theory which suggests carrier-mediated transport. 

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