Danazol increases the oral bioavailability of midazolam by inactivation of hepatic and intestinal CYP3A in rats.

Danazol (DNZ) is a synthetic androgen derivative used for the treatment of intractable hematological disorders. In this study, we investigated the effects of DNZ on CYP3A activity in hepatic and small intestinal microsomes and the pharmacokinetics of midazolam (MDZ), a typical substrate for CYP3A, in rats.MDZ 4-hydroxylation activities in hepatic and small intestinal microsomes significantly decreased 24 h after DNZ (100 mg/kg, i.p.) treatment. Time-dependent inactivation of MDZ 4-hydroxylation activities was noted when microsomes were pre-incubated with DNZ in the presence of a NADPH-generating system.The Western blot analysis indicated that the decrease observed in enzyme activity was not due to changes in the protein expression of CYP3A.In contrast to the intravenous administration, serum MDZ concentrations in DNZ-treated rats were markedly higher than those in control rats when administered orally. DNZ treatment increased MDZ oral bioavailability by approximately 2.5-folds.We herein demonstrated that DNZ increased the bioavailability of orally administered MDZ through irreversible inactivation of hepatic and intestinal CYP3A in rats.

Relationship between Oral Assessment Guide score and hypoalbuminemia in newly hospitalized patients.

This cross-sectional study investigated the relationship between Oral Assessment Guide (OAG) scores and malnutrition in newly hospitalized patients. A total of 880 hospitalized adults were enrolled. Hypoalbuminemia was defined as serum albumin less than 3.5 g/dL. Patients with hypoalbuminemia were older (P < 0.001), had a higher prevalence of respiratory diseases (P < 0.01), a higher prevalence of digestive diseases (P < 0.01), a lower prevalence of oral feeding (P < 0.001), a lower body mass index (P < 0.001), and higher OAG scores (P < 0.001) than those without hypoalbuminemia. Multivariate logistic regression analyses showed that the prevalence of hypoalbuminemia was significantly related to age (odds ratio [OR] = 1.05, P < 0.001), absence of oral feeding (OR = 2.72, P < 0.001), presence of respiratory diseases (OR = 2.53, P < 0.01), presence of digestive diseases (OR = 1.64, P < 0.01), and OAG scores (OR = 1.14, P < 0.01). Regarding OAG scores, the OR of hypoalbuminemia was greater in patients with disorders (scores 2 or 3) of swallowing (vs. score 1, OR = 1.83, P < 0.05) and saliva (vs. score 1, OR = 1.51, P < 0.05). There appears to be a positive association between OAG scores and hypoalbuminemia in hospitalized patients.