Predicción “in silico” de la absorción de fármacos en pacientes celiacos

  1. GOROSTIOLA, Marina 1
  2. GARCÍA SÁNCHEZ, María José 1
  3. SANTOS BUELGA, María Dolores 1
  1. 1 Departamento de Ciencias Farmacéuticas. Facultad de Farmacia. Campus Miguel de Unamuno. 37007 Salamanca.
Revue:
Farmajournal

ISSN: 2445-1355

Année de publication: 2018

Volumen: 3

Número: 1

Pages: 87-97

Type: Article

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D'autres publications dans: Farmajournal

Résumé

Celiac disease is known to cause impaired oral drug absorption as a consequence of the abnormal gastrointestinal function present in such patients. Nevertheless, the causes underlying this phenomenon remain relatively uncertain. The aim of this study was to determine by means of in silico methods, which factors are more likely to cause absorption irregularities in celiac patients. A simulation tool – Simcyp V14 – was used to predict absorption defects. Jejunum luminal pH and gastric emptying time data was collected from past reports to generate two pairs of virtual populations (celiac and control). Four drugs (desipramine, clozapine, digoxin and warfarin) with different physical-chemical properties were tested. Eight pairs of simulations were performed, divided in two sets to analyse separately the prospective influential factors pH and gastric emptying time. The absorption profiles were compared in terms of Cmax, tmax and AUC. No statistically significant differences (p<0.01) were found between control and celiac populations regarding jejunal pH differences. However, statistically significant differences (p<0.01) in terms of tmax were found regarding gastric emptying time differences with all drugs tested. Further studies need to be conducted to determine the clinical relevance of these results, and to analyse other possible factors involved.

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