OBJECTIVES: This study aims (i) to investigate the effects of EGCG on nadolol pharmacokinetics (maximum plasma concentration, time to achieve maximum concentration, area under the time-plasma concentration curve, plasma half-life and total clearance) and subsequently its impact on blood pressure control; and (ii) to identify transcriptional regulatory roles of EGCG on the nadolol intestinal and hepatic drug-transporters in SHR.
METHODS: Male SHR were pre-treated with a daily dose of EGCG (10 mg/kg body weight, i.g.) for 13 days. On day-14, a single dose of nadolol (10 mg/kg body weight) was given to the rats 30 min after the last dose of EGCG administration. Systolic blood pressure (SBP) was measured at 6-h and 22-h post-nadolol administration. Plasma and urinary nadolol concentrations were quantified using high-performance liquid chromatography, and pharmacokinetic parameters were analyzed by using non-compartmental analysis. Hepatic and ileal Oatp1a5, P-gp, and Oct1 mRNA expressions were determined by real-time PCR.
RESULTS: SBP of SHR pre-treated with EGCG and received nadolol was significantly higher than those which were not pre-treated with EGCG but received nadolol. Pre-treatment of EGCG resulted in a marked reduction of plasma nadolol maximum concentration (Cmax) and area under the time-plasma concentration curve (AUC) by 53% and 51% compared to its control. The 14-day treatment with oral EGCG led to a significant downregulation of mRNA levels of ileal Oatp1a5, P-gp, and Oct1 genes by 4.03-, 8.01- and 4.03-fold; and hepatic P-gp, and Oct1 genes by 2.61- and 2.66-fold.
CONCLUSION: These data concluded that exposure to EGCG could lead to reduced nadolol bioavailability and therefore, uncontrolled raised blood pressure and higher risks of cardiovascular events. Our data suggest that the reduced nadolol bioavailability is associated with the downregulation of ileal Oatp1a5 and Oct1 mRNA levels that subsequently lead to poor absorption of nadolol to the systemic circulation.
DESIGN AND METHODS: This is a cross-sectional study conducted among 184 eligible hemodialysis patients at four dialysis units in Malaysia. Three days dietary recall were used in the analysis of dietary intake and behavior. Sleep quality was assessed through Pittsburgh Sleep Quality Index.
RESULTS: More than half of the patients were poor sleepers. Among the sleep components, sleep latency affected patients the most, with the use of sleep medications was relatively low. A majority of the patients had inadequate dietary intake of energy (88%) and protein (75%). Dietary protein, potassium adjusted for body weight, and sodium intake were significantly increased in poor sleepers. Lower percentage of energy from carbohydrates; higher percentage of energy from fats; higher intakes of dietary protein, fat, phosphorus, and sodium were correlated with poorer sleep quality and its components. Skipping dinner on non-dialysis days and having supper on dialysis days were associated with poor sleep quality.
CONCLUSION: Poor sleep is prevalent among hemodialysis patients. Sleep quality of hemodialysis patients was highly associated with certain dietary factors. Periodical assessment of sleep quality and dietary intake is necessary to identify poor sleepers with inappropriate dietary intake to allow effective clinical and nutritional interventions to improve the sleep quality and nutritional status of these patients.