SUMMARY The effect of oral omeprazole on pentagastrin stimulated gastric acid secretion was studied in 11 healthy subjects. Doses of 20-80 mg produced dose dependent inhibition of acid secretion, with total suppression at the highest dose. Omeprazole was absorbed and eliminated from plasma rapidly and the inhibitory effect was related to the area under the plasma concentration time curve. The duration of action was long and single doses of 20 and 40 mg reduced acid secretion significantly for one and three days, respectively. Omeprazole in a dose of 15 mg given once daily for five days, suppressed acid secretion continuously, the inhibitory effect stabilising after three days at a predose inhibition of about 30% and a postdose inhibition of about 80%.Substituted benzimidazoles inhibit gastric acid secretion in several animal species, both in vitro and in vivo. In vitro data from isolated gastric glands support a novel mechanism of action as substituted benzimidazoles inhibit acid secretion produced by histamine, carbachol, dibutyryl cyclic AMP, and high concentrations of potassium. This suggests an intracellular site of action peripheral to cyclic AMP and close to the acid formation process.1-5 It has been postulated that the gastric proton pump at the secretory membrane of the parietal cell is an enzyme, (H' K+)ATPase, and substituted benzimidazoles appear to interfere with this pump.8 One substituted benzimidazole, H149/94, has been shown to inhibit basal acid output in vivo in man as well as the gastric acid response to pentagastrin stimulation. This effect was dose dependent and long lasting, despite rapid disappearance of H149/94 from the plasma.9In vitro omeprazole (H168/68) (Fig. 1), another substituted benzimidazole, is 10 times more potent than H149/94 on a molar basis. The present studies were designed to evaluate the effects of single and repeated oral doses of omeprazole on pentagastrin stimulated acid secretion in man. Methods SUBJECTSEleven men median age 29 years (range 22-38 years) and median weight 74 kg (range 63-88 kg) were studied. None had any history suggestive of peptic ulcer disease and all were considered healthy based on a physical examination, ECG, and a laboratory screen. During the first series of experiments the ECG, blood pressure, and pulse rate were recorded, and during all experiments the subjects were asked to report any noted effects. The study was approved by the Ethical Committee of the

The absorption of acetylsalicylic acid (ASA) from two different enteric-coated dosage forms, tablets (Premaspin) and granules (Reumyl), was studied in healthy volunteers under fasting and non-fasting conditions by following the plasma concentration and urine recovery of salicylates after single doses of ASA 1 g. Conventional tablets (Aspirin) were used as the reference. Under fasting conditions the absorption of ASA from the two different enteric-coated preparations was complete. Taken with food the enteric-coated tablets gave much lower plasma concentrations than under fasting conditions, and absorption was not complete in all subjects. In contrast, absorption from the enteric-coated granules was not influenced by the intake of food. It was concluded that enteric-coated granules of ASA permit more reproducible absorption than enteric-coated tablets.

The effect of oral iron prophylaxis on haemoglobin concentration (Hb) and haematocrit (Hct) has been studied in 300 pregnant women. From the 3rd to 4th month of pregnancy and until term the women were randomly treated with 100 mg or 200 mg ferrous iron daily respectively as sustained-release tablets (Duroferon Duretter ) or 200 mg ferrous iron as rapidly disintegrating tablets. All three treatments gave the same effect on Hb and Hct. This was true irrespective of the initial Hb. It was concluded that even the 100 mg dose was sufficient to cover the increased iron demands during pregnancy and to give an increase in Hb in anemic patients. The frequency of side-effects was lower in the two groups receiving the sustained-release tablets. The changes in Hb with time during pregnancy in relation to the initial iron status are discussed and some practical conclusions concerning the interpretation of the effect of iron supplementation during pregnancy are drawn.

The correlation between the magnitude of the increase of serum iron after an oral dose of iron and the total absorption of iron was studied in 51 healthy subjects and 10 patients with iron deficiency anaemia. 59Fe-labelled solutions of ferrous sulphate (25-100 mg iron) were administered to the fasting subjects. The serum iron concentration was followed for 4-6 hours and the absorption was measured in a whole-body counter.Good correlation was found between the maximal increase of serum iron and the total amount of iron absorbed after a dose of iron given as a solution. The serum iron method may be used for comparisons of the absorbability of different doses of iron by performing cross-over studies in groups of subjects. However, it was found that in an individual subject the serum iron method could not be used to determine the amount of iron absorbed from an oral dose of iron.

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