Investigation of drug absorption from the gastrointestinal tract of man. I. Metoprolol in the stomach, duodenum and jejunum.

Abstract

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.

Exploring gastrointestinal variables affecting drug and formulation behavior: Methodologies, challenges and opportunities

“…Disappearance of the drug over time in the aspirated intestinal fluid and appearance in the plasma indicated intestinal absorption. Approximately 60% of drug that was emptied from the stomach was absorbed from the duodenum, whereas 50% of metoprolol that left from the duodenum was absorbed from the proximal jejunum (Jobin et al, 1985). A more refined technique to study human permeability for different drug compounds is the Loc-I-Gut ® perfusion technique.…”

The gastrointestinal absorption of drugs in man: a review of current concepts and methods of investigation.

“…This intubation technique has been used primarily to investigate the GI absorption of nutrients but has been applied for the first time to drug absorption by our research group. In a study involving metoprolol (Jobin et al, 1985) we were able to show that: (1) the drug is not absorbed from the stomach; (2) most of the amount of drug leaving the stomach is absorbed in approximately 90 cm of the small intestine (roughly two thirds of this amount is absorbed in the duodenum, and one half of the amount leaving the duodenum is absorbed in the jejunum); and (3) the rate of absorption in each intestinal segment is controlled by the rate of delivery to that segment.…”

Investigation of drug absorption from the gastrointestinal tract of man. IV. Influence of food and digestive secretions on metoprolol jejunal absorption.

“…Other studies in this series have shown that food modifies the absorption rate of metoprolol, the rate being lower in the jejunum after perfusion below an occlusive balloon of a saline solution containing drug (Vidon et al, 1985) than after bolus administration into the stomach together with a homogenized meal (Jobin et al, 1985). Since the occlusive balloon prevented digestive secretions from reaching the jejunal segment where the metoprolol solution was perfused, it was not possible to determine from this latter study whether the higher absorption rate was due to the presence of nutrients, digestive secretions, or both.…”

“…H.p.l.c. methods were used to assay metoprolol in intestinal fluid (Jobin et al, 1985), and metoprolol and its a-hydroxy metabolite in plasma (Lecaillon et al, 1984). Urinary concentrations of a-hydroxymetoprolol and of the 4-phenylacetic acid metabolite were determined by the method of Godbillon & Duval (1984).…”