Abstract
A 90-year-old woman with reflux oesophagitis had been receiving a regimen of a generic brand of lansoprazole (15 mg/day), an aspirin tablet (81 mg), and anti-hypertensive medicines. In 2008 she underwent a gastroduodenoscopic examination more than 3 hours after ingesting these medicines. The endoscopy revealed white substances in the antrum and an oval-shaped agglomeration of granules in the stomach body. No specific findings such as pylorus stenosis were confirmed. Because the lansoprazole capsule was designed to dissolve in the intestine, the therapeutic concentration could not be obtained in the blood until 3 hours after the ingestion. When prescribing medication for elderly people with gastrointestinal hypomotility, physicians should note the bioavailability of the drugs, especially when using delayed-release capsules with enteric-coated granules inside.
BACKGROUND
Elderly people commonly manifest delays in the gastric emptying of ingested foods in association with other influencing factors, such as diabetes mellitus, gastro-oesophageal reflux disease (GORD) and medication.1–4 However, little has been done to assess these delays in patients aged 80 years and over.2
Elderly people are likely to develop GORD; hence, medications against GORD are on the rise. Proton-pump inhibitors (PPIs) are accepted as first-line drugs for clinical efficacy in the treatment of reflux oesophagitis and GORD. Because PPIs are unstable in acidic environments, they are provided as enteric-coated formulae. Lansoprazole is a PPI administered in the form of enteric-coated granules inside capsules. The granules are 1.1 mm in diameter and rapidly dissolve after leaving the stomach. By chance, we endoscopically observed lansoprazole granules in the stomach more than 3 hours after the patient ingested the PPI capsule.
CASE PRESENTATION
A 90-year-old woman with reflux oesophagitis underwent a gastroduodenoscopic examination on 21 March 2008 at the Kamifukuoka Kyodo clinic. We had asked her to miss her prescribed medicines (a generic brand of lansoprazole capsule (15 mg), an aspirin tablet (81 mg) and anti-hypertensive medicines) on the morning before the examination. Forgetting to comply with this request on the day of the examination, she took the medicines and failed to inform us that she had done so; therefore, she underwent the gastroduodenoscopy 3 hours or more after the ingestion. The endoscopic procedure revealed white substances in the antrum (fig 1), as well as an oval-shaped agglomeration of granules in the stomach body (fig 2). The endoscopy also showed signs of gastritis in the gastric mucosa, although no pyloric stenosis was verified.
Figure 1.
White substances observed in the antrum.
Figure 2.
An oval-shaped agglomeration of granules observed in the stomach body.
DISCUSSION
The delay in gastric emptying in elderly patients is a well-known phenomenon, although most studies indirectly observed such a delay using radiologic methods.5,6 However, recent developments in capsule endoscope enabled us to directly observe gastric transit.7 We reported the endoscopically proven delay of more than 3 hours in gastric emptying in an elderly patient.
We usually examine dyspeptic patients after overnight fasting with no medications in the morning. By keeping the gastroduodenal lumen empty, we can easily observe the gastroduodenal mucosa. With the exception of rare pathological conditions such as pylorus stenosis, our patients do not show prolonged stasis of food in the stomach during the endoscopic examination. In healthy adults, lansoprazole administered after an overnight fast can be detected in the form of its un-metabolites in the plasma within 1 hour of ingestion.8 Lansoprazole appears in the blood more slowly when ingested after a meal than it does under fasting.8 Because the lansoprazole capsule is designed to dissolve in the intestine, and because lansoprazole is rendered biologically unavailable in the acidic environment of the stomach, the therapeutic concentration could not be obtained in the blood of our patient until 3 hours after the ingestion. When ingested after eating, an even longer delay in drug-absorption can be expected.
In addition to gastroduodenal hypomotility, the size of the ingested medicine also influences the efficacy of PPIs. Because medicine granules >2 mm in diameter pass through the stomach more slowly than granules <2 mm in diameter,9 a diameter <2 mm appears suitable for intestinally soluble medicines. The size of this enteric-coated granule was 1.1 mm and meets this requirement. In finding the oval-shaped agglomeration of granules in our patient, we speculate that three mechanisms contributed to this delay in absorption. First, the outer coating of the capsule could hardly resolve in the stomach within the acceptable time. Second, the gastric hypomotility in this patient prevented the advance of the ingested contents onward to the intestine. Third, the hypomotility and hypometabolism resulted in the delayed anti-acid effect of lansoprazole and, thereby, failed to melt the outer membrane within the stomach. Given that we observed remnants of other medicines in the antrum, the lansoprazole capsule apparently could not resolve in the stomach within an acceptable time.
Other lansoprazole formulae are now supplied to provide sufficient bio-availability. Intra-orally disintegrated tablets of lansoprazole (Prevacid Solu Tab, Takeda Pharmaceutical Company Ltd, Japan) contain enteric-coated fine granules sized 0.35 mm in diameter. Because these fine granules disperse from the tablet within the mouth, they easily pass the oesophagus, stomach and intestine. However, the enteric-coated granules of the capsule formulae can only disperse after the outer coating has melted in the stomach. To obtain appropriate blood concentration of lansoprazole, intra-orally soluble tablets appear suitable for elderly people with hypomotility of the digestive canal.
LEARNING POINTS
Elderly people manifest poor gastrointestinal motility—a condition that slows drug disposition.
Prescription of proton-pump inhibitors are on the rise for the treatment of oesophagitis and GORD in the elderly.
Proton-pump inhibitors are labile in acidic environments.
To reach the intestine within acceptable time, an appropriate formula for proton-pump inhibitors should be established for the elderly.
Acknowledgments
We are grateful for Takeda Pharmaceutical Company Ltd for providing product data on lansoprazole.
Footnotes
Competing interests: none.
Patient consent: Patient/guardian consent was obtained for publication.
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