The results show that chemotherapy can add to both quantity and quality of life in advanced gastric cancer. The number of patients who benefit from treatment is, however, still rather limited.

The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug–drug interactions. Predicting potential interactions with OATPs is, therefore, of value. Here, we developed in vitro and in silico models for identification and prediction of specific and general inhibitors of OATP1B1, OATP1B3, and OATP2B1. The maximal transport activity (MTA) of each OATP in human liver was predicted from transport kinetics and protein quantification. We then used MTA to predict the effects of a subset of inhibitors on atorvastatin uptake in vivo. Using a data set of 225 drug-like compounds, 91 OATP inhibitors were identified. In silico models indicated that lipophilicity and polar surface area are key molecular features of OATP inhibition. MTA predictions identified OATP1B1 and OATP1B3 as major determinants of atorvastatin uptake in vivo. The relative contributions to overall hepatic uptake varied with isoform specificities of the inhibitors.

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

Laparoscopic cholecystectomy has rapidly become established as the treatment of choice for cholecystolithiasis. There is very little evidence, however, to support the claimed benefit to patients. In the present study 30 consecutive patients below the age of 65 years without acute cholecystitis and with no signs of common bile duct stones were randomized to laparoscopic or conventional open cholecystectomy. Median (interquartile range) intravenous consumption of pethidine with a patient-controlled injection device between 13 and 24 h after surgery was 125 (62-175) mg in patients who underwent the laparoscopic procedure and 200 (150-250) mg in those who had open operation. Urinary adrenaline and cortisol levels as well as those of plasma glucose, C-reactive protein and interleukin 6 were increased after surgery in both groups of patients, but without any significant difference between them. The mean(s.d.) duration of postoperative hospital stay (2.8(0.8) versus 1.8(0.6) days) and sick leave (24.0(4.4) versus 11.7(4.1) days) was significantly longer with open than laparoscopic cholecystectomy. The findings demonstrate obvious advantages of laparoscopic surgery as regards postoperative pain and convalescence, although factors reflecting the magnitude of trauma did not differ.