The defensive factors that prevent the human duodenal mucosa from acidic and peptic damage have not been fully evaluated. To determine whether duodenal mucosal bicarbonate production was altered in patients with inactive duodenal ulcer, we measured basal and acid-stimulated bicarbonate output from the duodenal bulb and the distal duodenum in healthy subjects and patients with inactive duodenal ulcer. As compared with 16 normal subjects, the 12 patients had significantly less mean (+/- SE) basal proximal duodenal mucosal bicarbonate secretion (185 +/- 13 vs. 107 +/- 18 mumol per centimeter per hour; P less than 0.001). Moreover, in response to a physiologic amount of hydrochloric acid (2 mmol per five minutes) instilled directly into the duodenal bulb, peak proximal duodenal bicarbonate output in the patients was 41 percent of the normal response (263 +/- 65 vs. 642 +/- 77 mumol per centimeter per hour; P less than 0.01). There was little overlap between groups. In contrast, bicarbonate outputs in the distal duodenum were similar in the two groups. We conclude that most patients with duodenal ulcer disease have decreased proximal duodenal mucosal bicarbonate production at rest, in response to hydrochloric acid, and in relation to peak gastric acid secretion. Impaired proximal duodenal mucosal bicarbonate secretion may be an important factor in the development and natural history of duodenal ulcer.
The pharmacokinetics and pharmacodynamics of lansoprazole, an antisecretory and antiulcer agent, were evaluated in 12 older (>60 years) and 12 younger (<60 years) healthy men.
Doses of lansoprazole (15 or 30 mg) or placebo were each given once daily for 7 consecutive days in this randomized, double‐blind, three‐way crossover study. Plasma concentrations and urinary excretion of lansoprazole and its metabolites, and gastric acid secretion were monitored after dosing on days 1 and 7 of each treatment period.
Within each age group, lansoprazole pharmacokinetics were linear. The mean clearance and elimination half‐life of lansoprazole were about 40% lower and higher, respectively, in the older subjects (CL0: 12–14 vs 20–24 1 h−1; t1/2;, z: 1.90–2.19 vs 1.26–1.44 h).
At each dose level, acid secretion was more inhibited in the older group. However, the AUC associated with a 50% decrease in acid secretion was similar (849 vs 892 ng ml−1 h) for both age groups. Multiple dosing decreased the maximum possible inhibition more in the older group than in the younger group.
Since the decrease in acid output associated with equivalent AUCs on day 1 was similar for the two age groups, the greater difference between day 1 and day 7 secretion in the older group indicates that recovery of secretory activity may decline with increasing age.
Human gastric bicarbonate secretion has been measured by back-titration, from pH and pressure of carbon dioxide (PCO2) determinations (using the Henderson-Hasselbalch formula), and from equations based on gastric juice osmolality and [H+] (osmolality-[H+] method). Since these methods show large quantitative differences in their estimations of gastric bicarbonate secretion, we examined each to define the reasons for these discrepancies and establish guidelines for future work in this area. Bicarbonate recovery from 'non-parietal' secretions (0 to 80 mM HCO3) reacting with 'pure parietal secretion' (160 mM HCl) was studied both in vitro and in the pylorus-occluded healthy human stomach during acid suppression, exogenous acidification, and pentagastrin stimulation. The pH/PCO2 method estimated HCO3- accurately under anaerobic conditions in vitro, whereas the osmolality-[H+] method (with correction factors for osmolality incorporated by us) was accurate under aerobic conditions. In the acid-suppressed stomach back-titration was significantly more accurate than the pH/PCO2 method. In the exogenously acidified and pentagastrin-stimulated stomachs the pH/PCO2 method underestimated bicarbonates, and the osmolality-[H+] method was spuriously elevated in the low range and diminished at high bicarbonate concentrations. Estimates of 'basal' bicarbonate secretion (at zero added bicarbonate) were severalfold higher by the osmolality-[H+] method (5.26 +/- 0.33 mmol/h) than by the pH/PCO2 method (1.20 +/- 0.23 mmol/h) or back-titration (0.65 +/- 0.14 mmol/h). In conclusion, gastric bicarbonate was determined most correctly by back-titration in the acid-suppressed stomach, whereas measurement of bicarbonate in the acid-secreting stomach was not accurate with any method.
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