Abstract
1 Gastrointestinal (GI) absorption of the β-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 non-absorbable 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.
2 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.
3 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.
4 The intubation technique appeared to be a suitable method for investigating drug absorption from the GI tract in man.
Keywords: drug absorption, metoprolol, stomach, duodenum, jejunum
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- Go V. L., Hofmann A. F., Summerskill W. H. Simultaneous measurements of total pancreatic, biliary, and gastric outputs in man using a perfusion technique. Gastroenterology. 1970 Mar;58(3):321–328. [PubMed] [Google Scholar]
- Hunt J. N., Stubbs D. F. The volume and energy content of meals as determinants of gastric emptying. J Physiol. 1975 Feb;245(1):209–225. doi: 10.1113/jphysiol.1975.sp010841. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jobin G., Cortot A., Danquechin-Dorval E., Godbillon J., Schoeller J. P., Bernier J. J., Hirtz J. Investigation of drug absorption from the gastrointestinal tract of man. V. Effect of the beta-adrenoceptor antagonist, metoprolol, on postprandial gastric function. Br J Clin Pharmacol. 1985;19 (Suppl 2):127S–135S. doi: 10.1111/j.1365-2125.1985.tb02753.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Longstreth G. F., Malagelada J. R., Go V. L. The gastric response to a transpyloric duodenal tube. Gut. 1975 Oct;16(10):777–780. doi: 10.1136/gut.16.10.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MacGregor I., Parent J., Meyer J. H. Gastric emptying of liquid meals and pancreatic and biliary secretion after subtotal gastrectomy or truncal vagotomy and pyloroplasty in man. Gastroenterology. 1977 Feb;72(2):195–205. [PubMed] [Google Scholar]
- Malagelada J. R., Go V. L., Summerskill W. H. Different gastric, pancreatic, and biliary responses to solid-liquid or homogenized meals. Dig Dis Sci. 1979 Feb;24(2):101–110. doi: 10.1007/BF01324736. [DOI] [PubMed] [Google Scholar]
- Malagelada J. R., Longstreth G. F., Summerskill W. H., Go V. L. Measurement of gastric functions during digestion of ordinary solid meals in man. Gastroenterology. 1976 Feb;70(2):203–210. [PubMed] [Google Scholar]
- Meeroff J. C., Go V. L., Phillips S. F. Control of gastric emptying by osmolality of duodenal contents in man. Gastroenterology. 1975 May;68(5 Pt 1):1144–1151. [PubMed] [Google Scholar]
- Rees W. D., Go V. L., Malagelada J. R. Simultaneous measurement of antroduodenal motility, gastric emptying, and duodenogastric reflux in man. Gut. 1979 Nov;20(11):963–970. doi: 10.1136/gut.20.11.963. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sioufi A., Leroux F., Sandrenan N. Gas chromatographic determination of metoprolol in human plasma. J Chromatogr. 1983 Jan 14;272(1):103–110. doi: 10.1016/s0378-4347(00)86107-1. [DOI] [PubMed] [Google Scholar]
- Wingate D. L., Sandberg R. J., Phillips S. F. A comparison of stable and 14 C-labelled polyethylene glycol as volume indicators in the human jejunum. Gut. 1972 Oct;13(10):812–815. doi: 10.1136/gut.13.10.812. [DOI] [PMC free article] [PubMed] [Google Scholar]