Gastrointestinal (GI) absorption of the beta‐adrenoceptor blocker metoprolol was investigated in five healthy subjects by means of an intubation method, employing a triple‐lumen tube introduced into the intestine, and a twin‐lumen tube in the stomach. Metoprolol was introduced into the stomach with a homogenized meal containing a nonabsorbable marker, [14C]‐PEG 4000, and another marker, PEG 4000, was perfused continuously into the duodenum just below the pylorus. Samples of GI contents were collected at regular intervals over 4 h in the stomach and at two different levels in the upper small intestine. Metoprolol was not absorbed from the stomach. Approximately 60% of the amount of drug emptied from the stomach was absorbed from the duodenum; about 50% of that leaving the duodenum was absorbed from the first part of the jejunum. The delivery process was the rate‐limiting factor of metoprolol absorption in these segments of the gut. Plasma concentrations reflected drug loss from the lumen and were higher in subjects exhibiting faster gastric emptying and higher absorption rates in the duodenum and jejunum. The intubation technique appeared to be a suitable method for investigating drug absorption from the GI tract in man.

Absorption of metoprolol in jejunum and ileum was investigated in eight healthy subjects using an intestinal perfusion technique below an occlusive balloon. An isotonic saline solution, with or without metoprolol, was perfused at a flow rate of 10 ml/min, either at the angle of Treitz or in the middle part of the ileum. The absorption in a 30 cm intestinal segment was evaluated at metoprolol concentrations of 20, 40 and 60 mg/l. Metoprolol did not affect gut motility. Metoprolol was similarly absorbed in the jejunum and ileum. The absorption rates appeared to be linearly related to the perfusion rates and to the mean concentration in the segment, indicating a first‐order kinetic process. The absorption rate of metoprolol perfused in the jejunum in a saline solution appeared to be lower than that observed after gastric administration of the drug incorporated in a meal. The findings in this and other studies in this series indicate that metoprolol is similarly absorbed throughout the small intestine.

1 The colonic absorption of metoprolol was indirectly evaluated by measuring drug appearance in plasma following intravenous, jejunal or colonic infusion in six healthy volunteers. Plasma concentrations of oa-hydroxymetoprolol and urinary excretion of the main metabolites were also measured. 2 Plasma profiles of metoprolol after colonic and jejunal perfusion were similar, and the relative bioavailabilities of the drug from these two regions of the gut were not significantly different. 3 The concentrations of a-hydroxymetoprolol, the major metabolite in plasma, were similar after jejunal and colonic perfusion, but higher than those observed after intravenous administration. 4 The percentage of the dose recovered in urine over 24 h as two metabolites was not significantly influenced by the route of administration.

The pharnacokinetic parameters of cefroxadin and cephalexin were compared after simultaneous oral administration of the two cephalosporins to 21 subjects.The influence of the dose, the formulation, and food intake on these parameters was investigated. Both drugs were equally well absorbed from all of the tested fornulations; identical percentages of the dose were recovered in the urine in all cases. The elimination half-life of cefroxadin and, consequently, the area under the plasma concentration-time curve were about 10% less than those ofcephalexin. Plasma concentrations and cumulative excretion curves of the two drugs were almost superimposable. Food intake had the same effect on both drugs; absorption was slowed, but the amounts absorbed were almost the same as those in fasted subjects.

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