Prednisolone absorption in coeliac disease

Pickup, M. E.; Farah, Fatima; Lowe, J. R.; Dixon, J. S.; Record, C. O.

doi:10.1007/bf03189406

Cited by 12 publications

(5 citation statements)

References 13 publications

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“…Highly variable prednisolone serum levels in patients with CD with higher disease activity could be attributed to altered CYP3A4 activity . Surprisingly, prednisolone absorption was not altered in patients with coeliac disease where absorptive surface area is reduced due to the villous atrophy …”

Section: Drug‐related Factors Affecting Absorption In Gi Diseasesmentioning

confidence: 97%

Impact of gastrointestinal disease states on oral drug absorption – implications for formulation design – a PEARRL review

Effinger

O’Driscoll

McAllister

et al. 2018

Journal of Pharmacy and Pharmacology

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Objectives Drug product performance in patients with gastrointestinal (GI) diseases can be altered compared to healthy subjects due to pathophysiological changes. In this review, relevant differences in patients with inflammatory bowel diseases, coeliac disease, irritable bowel syndrome and short bowel syndrome are discussed and possible in vitro and in silico tools to predict drug product performance in this patient population are assessed. Key findings Drug product performance was altered in patients with GI diseases compared to healthy subjects, as assessed in a limited number of studies for some drugs. Underlying causes can be observed pathophysiological alterations such as the differences in GI transit time, the composition of the GI fluids and GI permeability. Additionally, alterations in the abundance of metabolising enzymes and transporter systems were observed. The effect of the GI diseases on each parameter is not always evident as it may depend on the location and the state of the disease. The impact of the pathophysiological change on drug bioavailability depends on the physicochemical characteristics of the drug, the pharmaceutical formulation and drug metabolism. In vitro and in silico methods to predict drug product performance in patients with GI diseases are currently limited but could be a useful tool to improve drug therapy. Summary Development of suitable in vitro dissolution and in silico models for patients with GI diseases can improve their drug therapy. The likeliness of the models to provide accurate predictions depends on the knowledge of pathophysiological alterations, and thus, further assessment of physiological differences is essential.

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Section: Drug‐related Factors Affecting Absorption In Gi Diseasesmentioning

confidence: 97%

Impact of gastrointestinal disease states on oral drug absorption – implications for formulation design – a PEARRL review

Effinger

O’Driscoll

McAllister

et al. 2018

Journal of Pharmacy and Pharmacology

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“…Coe liac patients may have absorbed more topical corticosteroids than control subjects and this could be responsible for the greater degree of adrenal suppression seen. The drugs propran olol and cephalexin appear to be better ab sorbed in coeliac patients [19,20] but pred nisolone absorption is not significantly differ ent from controls [21].…”

Section: Discussionmentioning

confidence: 99%

Clinical, Biochemical and Morphological Responses of Patients with Villous Atrophy to Oral Betamethasone Valerate and Clobetasone Butyrate

Bramble¹,

Watson²,

Scott³

et al. 1981

Digestion

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10 patients with sub-total villous atrophy were given the topical corticosteroids betamethasone valerate or clobetasone butyrate for a period of 4 months whilst continuing on a normal diet. 5 patients improved symptomatically while red cell folate, urinary xylose and faecal fat excretion also improved. Brush border enzymes increased in patients treated with higher dosages of each drug. Enterocyte height increased and intra-epithelial lymphocytes were significantly decreased although overall morphological appearances remained indistinguishable from untreated coeliac disease. Suppression of the pituitary adrenal axis occurred in 8 patients and there did not appear to be useful separation of topical from systemic activity. These compounds offer no advantage over prednisolone in non-responsive coeliac disease.

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“…Malabsorption of prednisolone cannot be ruled out, since comparative intravenous studies were not performed. However, the normal bioavailability of prednisolone in.the two previous studies (2,3) suggests that malabsorption of prednisolone is not an important cause of the decreased C,,, and AUC,,, in the present celiac disease patients. The differences are best explained by an increased volume of distribution secondary to the hypoalbuminemia and the reduced serum protein-binding found in these patients.…”

Section: Resultsmentioning

confidence: 61%

Bioavailability of Prednisolone in Patients with Intestinal Malabsorption: The Importance of Measuring Serum Protein-Binding

Bergrem¹,

Opedal²

1983

Scandinavian Journal of Gastroenterology

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The effect of intestinal malabsorption on the oral bioavailability of prednisolone has been studied in six patients with celiac disease and in six patients with malabsorption of various etiologies, five of whom had undergone gut resections. The serum protein-binding of prednisolone was measured in five patients with celiac disease and hypoalbuminemia and in eight healthy controls. Compared with the controls, patients with celiac disease had a 22% lower peak serum prednisolone concentration (p less than 0.05) and a 16% smaller area under the time-concentration curve of total prednisolone (NS). The proportion of free prednisolone was 79% greater in patients with celiac disease (p less than 0.01), and the area under the time-concentration curve of free, biologically active prednisolone 53% larger (p less than 0.05). There were no significant differences in peak prednisolone concentration or area under the time-concentration curve between the controls and the other patients with malabsorption, who all had normal serum albumin concentrations. These results indicate that the absorption of prednisolone in patients with malabsorption is normal and that the apparently reduced bioavailability in celiac disease patients is more likely to be due to an increased volume of distribution secondary to hypoalbuminemia and reduced protein-binding.

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Prednisolone absorption in coeliac disease

Cited by 12 publications

References 13 publications

Impact of gastrointestinal disease states on oral drug absorption – implications for formulation design – a PEARRL review

Impact of gastrointestinal disease states on oral drug absorption – implications for formulation design – a PEARRL review

Clinical, Biochemical and Morphological Responses of Patients with Villous Atrophy to Oral Betamethasone Valerate and Clobetasone Butyrate

Bioavailability of Prednisolone in Patients with Intestinal Malabsorption: The Importance of Measuring Serum Protein-Binding

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