Absorption profiles and intestinal toxicological assessment of hydrochlorothiazide (HCT).

ONNAINTY RENEE; SCHENFELD ESTEBAN; PETITI J.; TORRES ALICIA; LONGHI M.; QUEVEDO MARIO ALFREDO; GRANERO G

Congreso; 76th FIP World Congress of Pharmacy and Pharmaceutical Sciences 2016.; 2016

HCT presents low bioavailability, with a large variation in this parameter, ranging from 60% to 80%, which is relatively dose proportional. This variable oral bioavailability may be attributed to its poor solubility and poor permeability. On based of these facts it was proposed to study intestinal absorption of the drug. In function of this oral variability, also was carried out a toxicity assay due to the reporters of HCT injuries on kidney epithelium.To determine the intestinal absorption profiles it was evaluated the drug permeability (Papp) in vitro and its effects on the intestinal mucosa.The permeability studies were performed with the everted rat intestinal sac model, at three concentrations levels of HCT (1; 17 and 178 µg/mL). After ended the permeability studies (17 µg/mL), sacs were evaluated histologically and ultrastructural by MOAR and TEM microscopy.Permeability profiles obtained with 178 µg/mL of HCT were lineal. While those one with 1 and 17 µg/mL showed exponential profiles, yielding two slope values, one from 10 to 60 min and the other from 70 to 120 min. These results correlated with microscopic studies as it was observed loss of the intestinal epithelium lining the villus together with abundant number of vacuoles and fenestrated capillaries in the connective tissue. These observations may explain that the increase of the Papp of the HCT is due to injuries produced in the intestinal tissue. It was demonstrated for first time a dose-depend permeability variability of HCT attributed to its toxic effects on the intestinal tissue. This research was carry out in the framework of a development of a PhD thesis.