The impact of advanced age on gastrointestinal characteristics that are relevant to oral drug absorption: An AGePOP review

Stillhart, Cordula; Asteriadis, Adam; Bocharova, E.N.; Eksteen, Gabriël; Harder, Fritz; Kusch, Jonas; Tzakri, Theodora; Augustijns, Patrick; Matthys, Christophe; Vertzoni, Maria; Reppas, Christos

doi:10.1016/j.ejps.2023.106452

Cited by 12 publications

(12 citation statements)

References 119 publications

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“…Aging is a condition predisposing to the development of both benign and malignant lesions in the upper gastrointestinal tract [4][5][6][7]. Indeed, a number of abnormalities of defensive factors on gastroduodenal mucosa were reported, and aggressive factors are increased in the elderly [1][2][3]. In this multicentre, crosssectional study, we updated data regarding the prevalence of endoscopic and histological lesions detected at upper endoscopy in a large, elderly population.…”

Section: Discussionmentioning

confidence: 99%

Upper endoscopy in elderly patients: a multicentre study.

Zullo,

De Francesco,

Amato

et al. 2024

Preprint

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Background: Both macroscopic and histological lesions are frequently detected at upper endoscopy in elderly patients. We assessed the prevalence of the main endoscopic and histological alteration in aged patients who underwent upper endoscopy. Methods: In this cross-sectional study, clinical, endoscopic, and histological features of consecutive elderly patients referred for upper endoscopy in clinical practice were retrieved. Data were analysed at both univariate and multivariate analyses. Results: A total of 1,336 (M/F: 595/741; Mean age: 74.1; range: 65-102) underwent upper endoscopy during one month in the 28 participating centres. At endoscopy, at least one macroscopic lesion was present in overall 420 (31.4%) patients. Erosive gastritis (13.3%) and erosive oesophagitis (9.8%) were the most prevalent lesions, whilst Barrett’s oesophagus, gastric ulcer, duodenal ulcer and erosive duodenitis were observed in 1.8%, 2%, 1.4%, and 3.1% patients, respectively. Nine (0.6%) cases of oesophageal, 25 (1.8%) gastric, and 2 (0.1%) duodenal neoplasia were detected. At histology, H. pylori infection was diagnosed in 99 (15.9%) patients, and extensive (antral plus corporal) precancerous lesions on gastric mucosa were detected in 80 patients (14.5%). Endoscopic lesions were more frequent in males, in patients who underwent first endoscopy, and in those with alarm symptoms, whilst were reduced in patients receiving PPI therapy. At multivariate analysis, no independent predictor was found. Conclusions: Our data found that frequency of erosive and neoplastic lesions remained high in elderly patients, whilst the prevalence of both H. pylori infection and peptic ulcer was decreased.

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Section: Discussionmentioning

confidence: 99%

Upper endoscopy in elderly patients: a multicentre study.

Zullo,

De Francesco,

Amato

et al. 2024

Preprint

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“…Lungs and the oral cavity can also affect absorption when inhaled, administered sublingually, or by means of an oromucosal spray. The possible characteristics of an aged stomach could be hypochlorhydria and a decreased volume of gastrointestinal fluids [ 188 , 189 ]. Although most in vivo studies suggested that the gastric emptying time increased in older adults [ 190 , 191 , 192 ], a conflicting study showed that the emptying rate of older adults remains within the same range as that of young adults [ 193 ].…”

Section: Cbd/thc Studies In Special Populationsmentioning

confidence: 99%

CBD and THC in Special Populations: Pharmacokinetics and Drug–Drug Interactions

Qian,

Beers,

Jackson

et al. 2024

Pharmaceutics

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Cannabinoid use has surged in the past decade, with a growing interest in expanding cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) applications into special populations. Consequently, the increased use of CBD and THC raises the risk of drug–drug interactions (DDIs). Nevertheless, DDIs for cannabinoids, especially in special populations, remain inadequately investigated. While some clinical trials have explored DDIs between therapeutic drugs like antiepileptic drugs and CBD/THC, more potential interactions remain to be examined. This review summarizes the published studies on CBD and THC–drug interactions, outlines the mechanisms involved, discusses the physiological considerations in pharmacokinetics (PK) and DDI studies in special populations (including pregnant and lactating women, pediatrics, older adults, patients with hepatic or renal impairments, and others), and presents modeling approaches that can describe the DDIs associated with CBD and THC in special populations. The PK of CBD and THC in special populations remain poorly characterized, with limited studies investigating DDIs involving CBD/THC in these populations. Therefore, it is critical to evaluate potential DDIs between CBD/THC and medications that are commonly used in special populations. Modeling approaches can aid in understanding these interactions.

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“…In the fasted state, the pH of gastrointestinal fluids is normally lower than fluids in other parts of the gastrointestinal tract because the proton pump secretes gastric acid that is required for the digestion of proteins. The reference data regarding pH values in gastric fluids in young and older adults are summarized in Table 1 [ 38 ]. The data from young and older adults on pH values in gastric fluids are summarized in the reference section [ 39 ].…”

Section: Gastrointestinal Fluid Volumes and Compositionmentioning

confidence: 99%

“…The pH values in the duodenum, measured using the Heidelberg capsule, were significantly lower in young adults compared with older adults [ 40 , 41 ]. The reference data regarding pH values in the duodenum, distal ileum and proximal colon fluids have been determined in young and older adults and are summarized in Table 2 [ 38 ]. In contrast, the pH measured in intestinal contents collected from volunteers, of which there were a limited number, was almost the same between older adults and young adults in a study conducted by Annaert et al [ 44 ].…”

Section: Gastrointestinal Fluid Volumes and Compositionmentioning

confidence: 99%

Simultaneous Prediction Method for Intestinal Absorption and Metabolism Using the Mini-Ussing Chamber System

Kondo,

Miyake

2023

Pharmaceutics

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Many evaluation tools for predicting human absorption are well-known for using cultured cell lines such as Caco-2, MDCK, and so on. Since the combinatorial chemistry and high throughput screening system, pharmacological assay, and pharmaceutical profiling assay are mainstays of drug development, PAMPA has been used to evaluate human drug absorption. In addition, cultured cell lines from iPS cells have been attracting attention because they morphologically resemble human intestinal tissues. In this review, we used human intestinal tissues to estimate human intestinal absorption and metabolism. The Ussing chamber uses human intestinal tissues to directly assay a drug candidate’s permeability and determine the electrophysiological parameters such as potential differences (PD), short circuit current (Isc), and resistance (R). Thus, it is an attractive tool for elucidating human intestinal permeability and metabolism. We have presented a novel prediction method for intestinal absorption and metabolism by utilizing a mini-Ussing chamber using human intestinal tissues and animal intestinal tissues, based on the transport index (TI). The TI value was calculated by taking the change in drug concentrations on the apical side due to precipitation and the total amounts accumulated in the tissue (Tcorr) and transported to the basal side (Xcorr). The drug absorbability in rank order, as well as the fraction of dose absorbed (Fa) in humans, was predicted, and the intestinal metabolism of dogs and rats was also predicted, although it was not quantitative. However, the metabolites formation index (MFI) values, which are included in the TI values, can predict the evaluation of intestinal metabolism and absorption by using ketoconazole. Therefore, the mini-Ussing chamber, equipped with human and animal intestinal tissues, would be an ultimate method to predict intestinal absorption and metabolism simultaneously.

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The impact of advanced age on gastrointestinal characteristics that are relevant to oral drug absorption: An AGePOP review

Cited by 12 publications

References 119 publications

Upper endoscopy in elderly patients: a multicentre study.

Upper endoscopy in elderly patients: a multicentre study.

CBD and THC in Special Populations: Pharmacokinetics and Drug–Drug Interactions

Simultaneous Prediction Method for Intestinal Absorption and Metabolism Using the Mini-Ussing Chamber System

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