Cimetidine blocks antacid-induced hypergastrinemia

The effects on fasting serum gastrin concentrations of hourly doses of magnesium and aluminum hydroxide antacid, with and without intravenous cimetidine, were determined in 8 patients with duodenal ulcer disease. Gastrin levels rose significantly over 10 h when antacid was given either as a bolus of 30 ml every hour or as a constant infusion of 0.5 ml/min (36 +/- 5 pg/ml and 33 +/- 6 pg/ml to 108 +/- 32 pg/ml and 109 +/- 22 pg/ml, respectively, p less than 0.05). This effect was specific for some component of the antacid and not for neutralization of acid per se, inasmuch as sodium bicarbonate, infused to keep gastric pH at levels at or above those of antacid, produced no significant rise in serum gastrin concentration. When intravenous cimetidine was administered simultaneously with intragastric antacid, gastrin levels did not rise. This occurred even though intragastric pH levels were actually higher with cimetidine plus antacid than with antacid alone. The ability of intravenous cimetidine to block antacid-induced hypergastrinemia was counteracted by infusing simultaneously both hydrochloric acid and antacid into the stomach. Since hydrochloric acid reacts with magnesium and aluminum hydroxide to form ionic magnesium and aluminum chloride, cimetidine most likely blocks antacid-induced hypergastrinemia by reducing acid secretion from the stomach and thereby limiting the generation of ionic magnesium and aluminum.     

Effect of optimum therapeutic dose of poldine on acid secretion, gastric acidity, gastric emptying, and serum gastrin concentration after a protein meal.

An oral optimum therapeutic dose of poldine was established in 5 normal subjects. Acid secretion in response to a protein meal was measured for 3 hr by continuous intragastric titration with sodium bicarbonate. Poldine 30 min before the meal reduced food-stimulated acid secretion from zero to 60% in the 5 subjects (average inhibition 32%). Poldine inhibited histamine-stimulated acid secretion to approximately the same extent. In separate experiments, gastric acidity after the meal was allowed to seek its natural level (i.e., there was notitration with bicarbonate). Poldine reduced average hydrogen concentration of the gastric contents by 85 to 50% from 1.5 to 3 hr after the meal. Since poldine did not alter the volume or the buffer content of the stomach, poldine inhibition of gastric acidity is due entirely to reduction of acid secretion and not to delayed emptying of food buffer. Poldine had no consistent effect on serum gastrin concentration after the meal when pH was maintained at a constant level by titration with bicarbonate; therefore, poldine inhibition of acid secretion is not mediated by a reduction of serum gastrin concentration.     

Meal-Stimulated Secretin Release in Man: Effect of Acid and Bile

Nine normal subjects were studied before and after intragastric instillation of a liquid meal. Gastric emptying rates of acid and pancreaticobiliary secretions were quantitated by means of a dilution indicator technique. A significant, positive correlation was found between load of acid to the duodenum and the concentration of secretin in plasma. No correlation was found between load of bile acids and plasma secretin. The buffering capacity of gastric contents should bc taken into account when fasting and postprandial period are compared. Plasma secretin concentration remained low during the first postprandial hour. Maximum secretin concentrations and duodenal disappearance rate of acid was observed 1 1/2-2 h after instillation of the meal. In contrast, trypsin output was maximum within 10 min. The data support the concept that in man release of secretin is governed principally by the amount of hydrogen ions emptied into duodenum and indicate the importance of secretin in the late postprandial period, when the acidity of the gastric contents is high.     

Comparison of an H2 receptor antagonist and a neutralizing antacid on postprandial acid delivery into the duodenum in patients with duodenal ulcer.

Measurement of the postprandial rate of acid delivery into the duodenum directly assessed the efficacy of two radically different acid-reducing therapies for duodenal ulcer disease. Cimetidine, 400 mg, with an ordinary solid meal decreased the 4-hr delivery of titratable acid and hydrogen ion into the duodenum by 63 and 86%, respectively (P less than 0.01 versus control). Liquid Maalox, 30 ml, 1 and 3 hr after an identical meal reduced 4-hr delivery of acid by 47 and 74%, respectively (P less than 0.01 versus control). During the study period, the H2 receptor antagonist effected a continuous reduction in gastric acidity and the delivery of acid into the duodenum. The liquid neutralizing antacid produced a more fluctuating decrease in these parameters. However, given in these dosages, the magnitude and duration of the acid-reducing effect were similar for both treatments.     

Effect of gastric alkalinization on serum gastrin concentrations in humans

Previous studies have shown that alkalinizing the stomach with sodium bicarbonate for periods up to 3 h does not cause an increase in serum gastrin concentration. We evaluated the effect of a 5-h period of continuous intragastric alkalinization on serum gastrin concentration in 12 healthy humans and 12 asymptomatic duodenal ulcer patients. On the first day, intragastric pH was maintained between 6.0 and 7.0 for 5 h by infusing 0.3 N sodium bicarbonate into the stomach. On the second day, an identical amount of sodium bicarbonate was infused intravenously while intragastric pH was permitted to remain at its natural level for 5 h. Serum gastrin concentration was also measured in each subject and patient after infusion of a homogenized steak meal. In both healthy subjects and duodenal ulcer patients, mean serum gastrin concentrations were significantly (p less than 0.05) higher after 5 h of intragastric bicarbonate infusion than after 5 h of intravenous bicarbonate infusion during which intragastric pH remained at its natural level. Increases in serum gastrin concentration with alkalinization averaged 23% and 30% of the increases in serum gastrin after a homogenized steak meal in the same subjects and patients, respectively. We conclude that continuous gastric alkalinization for 5 h increases serum gastrin concentrations in humans.     

Different gastric,pancreatic, and biliary responses to solid-liquid or homogenized meals

We have compared responses to an ordinary solid-liquid (S) meal and to a homogenized (H) meal of identical composition (sirloin steak, bread, butter, ice cream with chocolate syrup, and water) by measuring simultaneously postprandial gastric, pancreatic, and biliary functions by marker-perfusion techniques. Responses to each (S or H) meals differed strikingly both in magnitude and pattern. S meals elicited a stronger early gastric secretory response (acid, pepsin, and volume) which compensated for faster initial emptying and resulted in higher gastric acidity and volume than after H meals. Further, nutrients ingested with S meals were emptied at a slower rate than H (as evidenced by a more gradual decline in intragastric buffer and osmolality, as well as time required for complete emptying of the meal). This, in turn, prolonged pancreatic and biliary responses since stimulation of these organs continued for as long as meal was delivered into the duodenum. However, early biliary outputs (gallbladder response) were less after S than H, probably because nutrients entered the duodenum more slowly and were initially diluted by rapidly emptying water. The physical characteristics of each meal (encompassing appearance, taste, and form of ingestion) probably accounted for early differences in digestive responses. Later, interactions between gastric (motor and secretory), pancreatic, and biliary functions played a major role. Our findings suggest that gastric, pancreatic, and biliary responses to liquid test meals introduced into the stomach may differ substantially from the presumably more physiological response to ordinary solid-liquid meals.Dr. Summerskill died March 9, 1977.This investigation was supported in part by Research Grant AM 6908 from National Institutes of Health.     

Fate of oral neutralizing antacid and its effect on postprandial gastric secretion and emptying.

The fate and neutralizing efficiency of oral antacids (aluminum and magnesium hydroxides) as well as their effect on postprandial gastric function were quantified in 6 patients with duodenal ulcer disease. We employed a double-marker technique for measurement of gastric secretion and emptying and combined this with back-titration of the gastric samples and analysis of aluminum to trace the fate of antacid in the stomach and duodenum. These studies show that: (a) antacid therapy with aluminum and magnesium hydroxides significantly increases gastric secretion; (b) intragastric neutralization of gastric acid produces a significant and substantial decrease in net acid output (acid secreted minus acid neutralized), but the beneficial effects of neutralization are partially offset by incomplete intragastric formation of aluminum trichloride; (c) most but not all of the ingested antacid is utilized in acid neutralization in the stomach (average 78.6% in our 6 patients); and (d) antacid therapy does not modify the absolute rate of postprandial gastric emptying, but increases dilution of gastric contents, expanding the intragastric volume. Thus, the fractional gastric emptying rate declines, and this, in turn, should enhance antacid utilization by delaying its emptying.     

Regional Postprandial Differences in pH Within the Stomach and Gastroesophageal Junction

Our objective was to determine regional differences in intragastric pH after different types of meals. Ten normal subjects underwent 27-hr esophagogastric pH monitoring using a four-probe pH catheter. Meals were a spicy lunch, a high-fat dinner, and a typical bland breakfast. The fatty dinner had the highest postprandial buffering effect, elevating proximal and mid/distal gastric pH to 4.9 ± 0.4 and 4.0 ± 0.4, respectively, significantly (P< 0.05) higher compared to 4.2 ± 0.3 and 3.0 ± 0.4 for the spicy lunch and 3.0 ± 0.3 and 2.5 ± 0.8 for the breakfast. The buffering effect of the high-volume fatty meal to pH > 4 was also longer (150 min) compared to that of the spicy lunch (45 min) and the bland breakfast, which did not increase gastric pH to > 4 at any time. Proximal gastric acid pockets were seen between 15 and 90 min postprandially. These were located 3.4 ± 0.8 cm below the proximal LES border, extending for a length of 2.3 ± 0.8 cm, with a drop in mean pH from 4.7 ± 0.4 to 1.5 ± 0.9. Acid pockets were seen equally after the spicy lunch and fatty dinner but less frequently after the bland breakfast. We conclude that a high-volume fatty meal has the highest buffering effect on gastric pH compared to a spicy lunch or a bland breakfast. Buffering effects of meals are significantly higher in the proximal than in the mid/distal stomach. Despite the intragastric buffering effect of meals, focal areas of acidity were observed in the region of the cardia–gastroesophageal junction during the postprandial period.     

Effect of ranitidine on basal and bicarbonate enhanced intragastric PCO2: a tonometric study.

A high intragastric PCO2 (iPCO2), determined tonometrically, is the main factor participating in a low gastric intramucosal pH (pHi) and may point to gastric mucosal ischaemia. iPCO2 might also increase, however, after buffering of gastric acid by bicarbonate; the magnitude of this effect and the efficacy of H2 blockers to prevent it are unclear. Ten healthy volunteers (20-24 years) were studied at baseline and after oral ingestion of 500 mg sodium bicarbonate. The same test was carried out one hour after intravenous injection of 100 mg ranitidine. A glass pH electrode for continuous gastric juice pH measurements and a Tonomitor catheter were placed 10 cm distally from the gastro-oesophageal junction. iPCO2 was measured in saline boluses, infused at 30 minute intervals in the balloon at the tip of the Tonomitor. Before ranitidine was given, basal iPCO2 (mean (SD)) was 8.40 (2.53) kPa, and increased to 19.20 (5.87) kPa after sodium bicarbonate (p < 0.001). After ranitidine, the gastric juice pH increased from 1.8 (0.9) to 5.6 (1.3) (p < 0.05), while basal iPCO2 was 5.60 (0.67) kPa (p < 0.01) and did not change after sodium bicarbonate (6.27 (2.67) kPa)). iPCO2 values after acid secretion suppression were similar to those in capillary blood (5.60 (0.40 kPa)). The difference between intragastric and blood PCO2 during normal acid secretion probably results from buffering of gastric acid by gastric bicarbonate, rather than by duodenogastric reflux or saliva entering the stomach. During acid secretion suppression, intragastric equals blood PCO2, even after oral ingestion of sodium bicarbonate. Hence, acid secretion inhibition is mandatory for proper assessment of iPCO2 and pHi as specific measures of the adequacy of gastric mucosal blood flow.     

Neutralizing capacity and cost effectiveness of antacids

The prescribing physician is faced with a wide choice of antacid preparations. To provide a guide, we tested the commonly available antacids, both liquid and tablet, for their acid-neutralizing capacity. We calculated the cost effectiveness of antacids and tabulated the cost of 1 month of therapy. The acid-neutralizing capacity and cost effectiveness of liquid antacids are generally better than tablet antacids. The most effective liquid antacids, which are composed of either aluminum and magnesium hydroxide mixtures or calcium carbonate, vary in buffering capacity from 3 to 4.2 meq/mL of antacid and range in monthly cost of therapy from $35 to $74. In contrast, the five least effective liquid antacids vary in acid-neutralizing capacity from 0.3 to 2.3 meq/mL of antacid and in monthly cost of therapy from $78 to $498. Because the monthly cost of therapy is influenced primarily by the acid-neutralizing capacity of the antacid, a high-potency antacid should be prescribed. The taste and sodium content of the antacids should also be taken into account by the prescribing physician.     

Reduction of twenty-four-hour gastric acidity with combination drug therapy in patients with duodenal ulcer.

Four "extra-effort" drug regimens were tested to determine which most nearly eliminated 24-hr gastric acidity in 8 patients with duodenal ulcer. The regimens included two 300 mg cimetidine tablets with meals and at bedtime; one 300 mg cimetidine tablet plus an anticholinergic drug with meals and at bedtime; 300 mg cimetidine with meals and at bedtime plus liquid antacid 1 and 3 hr after meals and at bedtime; and 300 mg cimetidine, an anticholinergic drug, and antacid, taken simultaneously as each meal was finished and at bedtime. No regimen completely eliminated gastric acidity. However, compared to standard cimetidine therapy (300 mg four times daily) which led to a median 24-hr pH of 2.6, each "extra-effort" regimen except cimetidine plus an anticholinergic was significantly better in reducing gastric acidity. During the daytime hours, cimetidine with meals plus antacid 1 and 3 hr after meals was most effective (median pH 5.0). However, the more convenient regimen of cimetidine, an anticholinergic drug, and antacid was almost as effective (median pH 4.3). None of the "extra-effort" regimens was significantly more effective than standard cimetidine therapy during the hours of sleep.     

Role of lipase in the regulation of postprandial gastric acid secretion and emptying of fat in humans: a study with orlistat, a highly specific lipase inhibitor

BACKGROUND AND AIMS: To investigate the importance of lipase on gastric functions, we studied the effects of orlistat, a potent and specific inhibitor of lipase, on postprandial gastric acidity and gastric emptying of fat. METHODS: Fourteen healthy volunteers participated in a double blind, placebo controlled, randomised study. In a two way cross over study with two test periods of five days, separated by at least 14 days, orlistat 120 mg three times daily or placebo was given with standardised daily meals. In previous experiments we found that this dose almost completely inhibited postprandial duodenal lipase activity. Subjects underwent 28 hour intragastric pH-metry on day 4, and a gastric emptying study with a mixed meal (800 kcal) labelled with (999m)Tc sulphur colloid (solids) and (111In)thiocyanate (fat) on day 5. Gastric pH data were analysed for three postprandial hours and the interdigestive periods. RESULTS: Orlistat inhibited almost completely (by 75%) lipase activity and accelerated gastric emptying of both the solid (by 52%) and fat (by 44%) phases of the mixed meal (p<0.03). Orlistat increased postprandial gastric acidity (from a median pH of 3.3 to 2.7; p<0.01). Postprandial cholecystokinin release was lower with orlistat (p<0.03). CONCLUSION: Lipase has an important role in the regulation of postprandial gastric acid secretion and fat emptying in humans. These effects might be explained by lipolysis induced release of cholecystokinin.     

Effects of a new effervescent cimetidine formulation on gastric acidity in healthy subjects

The effect of a new effervescent formulation of 800 mg cimetidine on intragastric acidity was studied in 10 fasting healthy male volunteers. Using a randomised, cross-over design, the effect of this new cimetidine formulation was compared with that of a standard dose of a liquid aluminium/magnesium hydroxide antacid (Maalox). Intragastric pH was continuously monitored with a combination glass electrode and a digital data recorder. After a baseline period of 1 h the effect of the drugs was studied for 5 h. Both drugs increased the intragastric pH instantaneously, but the effect of Maalox ceased after 45.3 +/- 31.0 min (mean +/- SD), whereas that of effervescent cimetidine persisted for the entire 5 hr study period. Time with pH greater than 3.5, time with pH greater than 2, greater than 3, greater than 4, greater than 5 and greater than 6, and areas under the pH-time curves were significantly (P less than 0.001) higher for effervescent cimetidine than for Maalox. It is concluded that the new cimetidine formulation studied effectively combines, at least in healthy male volunteers, the immediate effect of a pH buffer with the prolonged systemic effect of an H2 blocker.     

Comparison of low-dose antacids,cimetidine, and placebo on 24-hour intragastric acidity in healthy volunteers

Low-dose aluminium (Al) antacids are effective in promoting ulcer healing and symptomatic relief in peptic ulcer patients, although the effect on intragastric acidity is very weak. In this randomized, double-blind study, 24-hr intragastric acidity was compared in 11 healthy volunteers, treated with a low-dose Al antacid regimen (1 tablet four times a day), cimetidine (800 mg at bedtime) and placebo, using the double-dummy technique. Standardized meals were given at 8am, noon, and 5pm. Medication was given 1 hr after meals and at bedtime. Intragastric acidity was recorded with a nasogastric monocrystant antimony pH catheter, connected to an ambulatory digital data recorder. No significant difference in intragastric acidity was observed between antacid and placebo treatment. Treatment with cimetidine reduced circadian and nocturnal (but not diurnal) intragastric acidity significantly, as compared to both placebo and antacid treatment. The results support the hypothesis that Al antacids promote peptic ulcer healing by other mechanisms than acid neutralization.     

A canine model for the study of gastric secretion and emptying after a meal

Our aim was to develop a chronic canine model that would serve for the simultaneous measurements of postprandial gastric secretion and emptying by a double-marker dilution technique without artificially interfering with intragastric pH. A constant duodenal perfusion of a nonabsorbable marker allowed determination of luminal flow and total recovery of a second marker ingested with a meal. By calculating the amount of meal marker remaining in the stomach and its dilution (by repeat gastric sampling), we could determine the volume of gastric contents. Acid concentration in gastric samples was measured by titrationex vivo, and gastric acid content was calculated by multiplying the volume of gastric contents by titratable acidity. In this model, net acid gain at each sampling interval indicates acid output. Acid and volume losses are equivalent to duodenal acid load ad emptying rate, respectively. The method has been validated by virtually abolishing the endogenous secretion of acid (by intravenous infusion of cimetidine) and the calculation of known volumes and concentrations of acid exogenously instilled in the animal's stomach. Our results indicate that this is an accurate and practical method for the physiologic measurement of postprandial gastric function in dogs. Further, these studies substantiate the validity of the assumptions upon which the human double-marker method was based.Supported in part by grant AM-26428 from the National Institutes of Health. Dr. Malagelada was the recipient of RCDA AM-00330 from the National Institutes of Health.     

Pharmacokinetics of isoniazid under fasting conditions, with food, and with antacids.

STUDY OBJECTIVES: To determine the intra- and intersubject variability in and the effects of food or antacids on the pharmacokinetics of isoniazid (INH). DESIGN: Randomized, four-period cross-over Phase I study in 14 healthy male and female volunteers. Subjects ingested single doses of INH 300 mg under fasting conditions twice, with a high-fat meal, and with aluminum-magnesium antacid. They also received standard doses of rifampin, pyrazinamide, and ethambutol. RESULTS: Serum was collected for 48 hours, and assayed by high performance liquid chromatography (HPLC). Data were analyzed using noncompartmental methods and a compartmental analysis using nonparametric expectation maximization. Both fasting conditions produced similar results: a mean INH Cmax of 5.53 +/- 2.92 microg/ml, Tmax of 1.02 +/- 1.10 hours, and AUC0-infinity of 20.16 +/- 12.45 microg x hr/ml. These findings are similar to those reported previously. Antacids did not alter these parameters significantly (Cmax of 5.62 +/- 2.53 microg/ml, Tmax of 0.71 +/- 0.56 hours, and AUC0-infinity of 20.27 +/- 11.39 microg x hr/ml). In contrast, the high-fat meal recommended by the Food and Drug Administration reduced INH Cmax by 51% (2.73 +/- 1.70 microg/ml), nearly doubled Tmax (1.93 +/- 1.61 hours), and reduced AUC0-infinity by 12% (17.72 +/- 10.32 microg x hr/ml). CONCLUSIONS: These changes in Cmax, Tmax, and AUC0-infinity can be avoided by giving INH on an empty stomach whenever possible.     

Antacid action of the aluminum cation: comparison of the in vitro effect of hydroxide and phosphate in open and closed systems

Antacid capacity of two aluminium containing-antacid drugs was evaluated in vitro; the first drug contained aluminium hydroxide (Alternagel), the second, aluminium phosphate (Phosphalugel). The antacid evaluation was performed 1) in a closed system by measuring antacid activity by down titration, 2) by a dynamic evaluation simulating acid secretion and gastric emptying. The results were reported both to the recommended therapeutical dose and to 100 mg aluminium. In static conditions, without gastric emptying, it was shown that aluminium hydroxide and phosphate acted by their buffer capacity in pH range less than or equal to pH 1.5. The therapeutical dose of aluminium phosphate displayed greater antacid activity than aluminium hydroxide, this fact being due to the empiric choice of the doses. With regard to aluminium content, aluminium phosphate activity remained greater than that of aluminium hydroxide although the difference decreased with decreasing pH values. The antacid capacities were related to the emptying outputs. Antacid activity corresponding to 100 mg aluminium was similar in both antacids less than pH 1.5. This effect was dependent on emptying rates. It can be suggested that Al was responsible for antacid activity in both preparations, and that the buffering capacity was supported by the change of aluminium cation in hydrolysis intermediary compounds.     

Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21st century

Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes, (e.g., giving unprotected enzymes at the start of the meal and acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy.     

Role of cholecystokinin in relaxation of the proximal stomach

Ingestion of a meal causes proximal gastric relaxation (accommodation). The magnitude of accommodation is related to the fat content of the meal. A role for cholecystokinin (CCK) has been suggested. However, under fasting conditions intravenous CCK to postprandial levels does not induce a similar accommodation. This study further explores the role of CCK in accommodation. A gastric barostat was used in eight healthy persons to study accommodation in response to a carbohydrate meal with intravenous CCK (CH-CCK), carbohydrate meal with intravenous placebo (CH-placebo) and a fat rich meal with intravenous placebo (FAT). VAS scores for satiety and plasma CCK levels were obtained. In the first postprandial hour the FAT meal induced a relaxation of 112 +/- 29 ml, the CH-CCK meal 49 +/- 36 ml and the CH-placebo meal 12 +/- 32 ml (FAT versus CH-placebo P = 0.03; FAT versus CH-CCK P = 0.09). In the second postprandial hour, intragastric bag volume returned to baseline with all meals. The FAT meal had the most pronounced effect with respect to satiety, CH-placebo the least. In the first postprandial hour, plasma CCK levels increased with the CH-CCK and FAT meals but not with the CH-placebo meal; in the second postprandial hour, levels remained elevated with the CH-CCK meal. It is concluded that a carbohydrate meal with exogenous CCK does not induce fundic relaxation, whereas a fat-rich meal (endogenous CCK) does, despite similar plasma CCK levels.     

Intraluminal pH in the stomach, duodenum, and proximal jejunum in normal subjects and patients with exocrine pancreatic insufficiency

In situ pH was measured simultaneously with microelectrodes in the stomach, duodenal bulb, midduodenum, duodenojejunal junction, and proximal jejunum. Fourteen healthy subjects and 8 patients with exocrine pancreatic insufficiency were studied under fasting conditions and for 3 h after a standard liquid meal. The luminal pH gradient was steepest in the proximal 10 cm of the duodenum, where acidity was reduced from pH 2 to pH 5 in the fasting state and from pH 1.7 to pH 4.3 in the second and third postprandial hour. Acidity was further reduced in the distal duodenum to a pH between 5 and 6 at the duodenojejunal junction. The frequent wide and rapid pH fluctuations seen in the duodenal bulb were gradually reduced along the duodenum and became rare in the jejunum. In patients with pancreatic insufficiency, duodenal or jejunal acidity did not differ significantly from the controls, with the exception of the single 10-min period occurring 70-80 min after the meal when duodenal bulb pH was 2.1 as compared with 3.1 in the normal subjects (p less than 0.05). All patients, including 2 patients with a very high duodenal acidity, demonstrated a duodenal pH gradient as steep as that found in the normal subjects, indicating sources of bicarbonate other than the pancreas.