Sufotidine 600 Mg Bd Virtually Eliminates 24 Hour Intragastric Acidity in Duodenal Ulcer Subjects Gut: First Published As 10.1136/Gut.31.3.291 on 1 March 1990
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Gut, 1990, 31, 291-293 291 Sufotidine 600 mg bd virtually eliminates 24 hour intragastric acidity in duodenal ulcer subjects Gut: first published as 10.1136/gut.31.3.291 on 1 March 1990. Downloaded from J T L Smith, R E Pounder Abstract (68 to 99-9 kg), their median height was 178 cm In a double blind study, 24 hour intragastric (164 to 189 cm), and two of the seven subjects acidity and 24 hour plasma gastrin concentra- smoked cigarettes (10 to 20 cigarettes per day). tions were measured simultaneously in seven Two other subjects withdrew from the study, duodenal ulcer subjects on the fifth day but both had been dosed only with placebo. The of receiving either sufotidine 600 mg bd or subjects were in symptomatic remission, and not placebo. Compared with placebo, during treat- taking antisecretory therapy. The study was ment with sufotidine 600 mg bd the median double blind, and dosing was given in a pre- integrated 24 hour intragastric acidity was determined random order. decreased by 95% (range 74% to 99%) from The subjects were studied twice, on the fifth 1000 to 51 mmol/h/l, whilst the median in- day ofdosing with either sufotidine 600 mg bd or tegrated 24 hour plasma gastrin concentration placebo. There was a nine day washout period increased from 416 to 927 pmol/h/l. between the studies, when the subjects received no treatment. Dosing was in the form of six identical tablets taken twice a day - at 0935 and First generation histamine H2-receptor blockers 1935 hours. Compliance with the dosing regimen cause a short lived pulse ofdecreased intragastric before the study day was encouraged by the use acidity.'1- Meta-analysis of the results of pub- of a long range paging system (British Telecom); lished studies has suggested that the more pro- each subject was paged at the recommended time found the drug induced decrease of nocturnal ofevery dose to remind him to take the tablets. intragastric acidity by a particular regimen, the The study was approved by the Ethics Com- greater the percentage of duodenal ulcers which mittee of the Royal Free Hospital and written are healed after four weeks oftreatment with that consent was obtained from each patient. Routine regimen. A new meta-analysis has suggested safety studies were performed before and after that the four week duodenal ulcer healing rate treatment with both drugs. http://gut.bmj.com/ can be predicted most accurately by a drug's The subjects were studied using the Royal ability to maintain 24 hour intragastric pH above Free Hospital standard protocol for 24 hour 3 (H+ activity below 1 mmol/1),7 suggesting that studies.'6 They were admitted for each study control ofdaytime acidity may also be important. to a research ward after an overnight fast. A This finding is supported by the fact that the 10 French gauge salem sump nasogastric tube highest four week duodenal ulcer healing rates (Argyle Medical) was positioned in the stomach. have been reported during treatment with 30 Aliquots (5-10 ml) of intragastric contents were on October 2, 2021 by guest. Protected copyright. to 40 mg/day of omeprazole,5 which inhibits aspirated hourly throughout the study (except at nocturnal and daytime acidity.9'0 Omeprazole 1000 and 2000 hours), and the pH ofeach aliquot has also had particular success in the manage- measured immediately to the nearest 0-01 pH ment of difficult duodenal ulceration, the more unit by means of a glass electrode and digital pH severe grades of oesophagitis, and the Zollinger meter (Radiometer, Copenhagen). The electrode Ellison syndrome," 14 because of the profound was calibrated with standard buffers (pH 7-00, antisecretory effect of this drug. 4-01, and 1-09: Radiometer, Copenhagen) before Sufotidine is a new competitive, long acting and halfway through each hourly batch of histamine H2-blocker.'5 Earlier healthy volunteer samples. studies, using single day dosing with sufotidine, Every hour from 0900 to 2400 hours, and two suggested that sufotidine 600 mg bd taken before hourly thereafter, blood was taken through a breakfast and at bed time could induce a sus- venous cannula for assay of plasma gasrin con- tained 24 hour decrease of acidity (J T L Smith centration. The blood was collected in lithium- and R E Pounder; H Merki; unpublished data). heparin tubes which contained 0-2 ml aprotinin The objectives of the present study were to (Trasylol, Bayer). The tubes were centrifuged observe the effects of repeat dosing with sufoti- immediately, the plasma transferred to plastic dine 600 mg bd on 24 hour intragastric acidity tubes and frozen to -20°C. All the plasma and plasma gastrin concentration in subjects samples from each subject were analysed for Academic Department of with a history of duodenal ulceration. in one Medicine, Royal Free gastrin batch, by radioimmunoassay Hospital School of using antibody GAS 179 in Professor Bloom's Medicine, London laboratory at the Hammersmith Hospital, J T L Smith Methods London. 17 R E Pounder During the study the subjects were fully Correspondence to: ENTS en- Dr R E Pounder, Royal Free PATI ambulant around the ward. The food and Hospital School of Medicine, Seven male subjects with a history ofendoscopic- vironmental conditions for both studies were Pond Street, London NW3 2QG ally confirmed duodenal ulceration completed identical to those used in earlier experiments at Accepted for publication the study; their median age was 53 years (range the Royal Free Hospital.'6 The following meals 6 June 1989 26 to 63 years), their median weight was 76 kg were served: breakfast, coffee, lunch, tea, dinner 292 Smith, Pounder and plasma gastrin concentration was tested using Spearman rank correlation. Differences occurring with a probability of 5% of less were considered significant. Gut: first published as 10.1136/gut.31.3.291 on 1 March 1990. Downloaded from E Results E Two subjects withdrew from the study, but both : were found to be taking placebo. The remaining seven subjects completed each part of the study, and no clinically significant abnormality was observed in any of the routine haematology or biochemistry profiles, before or after dosing with either placebo or sufotidine. 9 10 11 12 13 14 15 16 17 18 19 2021 22 23 24 1 2 3 4 5 6 7 8 Time (h) INTRAGASTRIC ACIDITY Figure 1: Median hourly 24 hour intragastric acidity profile in seven subjects with a history of Figure 1 shows the hourly median intragastric duodenal ulcer on thefifth day ofdosing with placebo (-O* or sufotidine 600 mg bd (O-O). B=breakfast; C=coffee; L =lunch; T=tea; D=dinner; N=nightcap. acidity on the fifth day of dosing with either placebo or sufotidine 600 mg bd. It shows that during dosing with sufotidine 600 mg bd there and a bedtime snack at 0915, 1115, 1315, 1615, was a consistent and profound decrease ofacidity 1915, and 2215 hours, respectively. throughout the 24 hours. Figure 2 shows that the median integrated 24 hour intragastric for the seven duodenal STATISTICAL ANALYSIS acidity 1600 ulcer with a Twenty four hour profiles of intragastric acidity subjects history of duodenal ulcera- n=7 tion during dosing with placebo was 1000 and plasma gastrin concentration were obtained 1400 P<0 001 mmol/h/l (range618-1449 mmol/h/l). On thefifth for every subject in each study period. No gastric 1200\ day of dosing with sufotidine 600 mg bd, inte- aspirates were taken at 1000 or 2000 hours to grated 24 hour intragastric acidity was decreased avoid aspirating drug hence, to calculate the 1000 1000 in 24 hour integrated acidity profiles, intragastric every subject to a median value of 51 mmolIhIl E (range 5-158 mmol/h/l; 95%; p 0-001). For the acidity values of 1-30 and 0 13 mmol/l were used seven subjects the decreases of 24 hour intra- at these times, respectively. The 1 30 and 0-13 600- gastric acidity ranged from 74% to 99%. http://gut.bmj.com/ mmol/l values represent the median intragastric The median intragastric acidity was above pH 400- acidity at 1000 and 2000 hours in 46 healthy 3 for 17% subjects, studied under identical conditions of the study, with an inter-subject 200 range of 8-33%. when receiving placebo at the Royal Free 0- 51 Hospital. The area under the time-concentration Placebo Suf 600mg bd curve for each profile was calculated by the Figure 2: Twentyfour hour PLASMA GASTRIN CONCENTRATION integrated intragastric trapezoid rule, with integrated acidity expressed The 24 hour profiles of median plasma gastrin on October 2, 2021 by guest. Protected copyright. acidity in seven subjects on as mmollhIl and integrated plasma gastrin as concentration on the fifth of thefifth day ofdosing with pmoIIhIl. To make these values comparable with day dosing with placebo or sufotidine 600 mg either placebo or sufotidine 600 mg bd are shown bd. single point measurements of either acidity or in Figure 3, which shows a consistent rise of gastrin, each value should be divided by 23. median plasma gastrin concentration throughout The significance of the difference between the the 24 hours during dosing with sufotidine. integrated 24 hour values were assessed using Figure 4 shows that the median integrated 24 Wilcoxon's matched-pair signed rank test. The hour plasma gastrin concentration for the seven correlation between integrated 24 hour acidity subjects during dosing with placebo was 416 pmoIIhIl (range 208-947 pmol/h/l); the concen- 80 tratons on the fifth day of dosing with sufotidine 600 mg bd had risen in every subject to a median 70- B C L of 927 pmol/h/Il (range 629-1951 pmol/h/l; p 0-001).