Drug-nutrient interactions最新文献

Gold (Au) thioglucose, used to treat inflammatory diseases such as rheumatoid arthritis, inhibits the selenium (Se)-dependent glutathione peroxidase. The present study examines the ability of Au to act either as a Se antagonist or as a GSH peroxidase inhibitor in vivo. The effects of gold thioglucose loading on Se distribution, and on Se-dependent GSH peroxidase and GSH S-transferase, were examined in rats fed three dietary levels of Se (0, 0.2, and 2.0 ppm), and with or without adjuvant-induced inflammation. Kidney, liver, spleen, testes, and erythrocytes were selected for study based upon their high Se content and their ability to concentrate Au. Au loading increased kidney, liver, and spleen Se concentrations, and this effect was dependent upon dietary Se levels. Rats fed Se-supplemented diets had higher levels of Au in kidney, liver, and spleens than did rats fed a Se-deficient diet. Au loading decreased GSH peroxidase activity in kidney, liver, and erythrocytes. The decrease in GSH peroxidase in kidney and liver, and the increase in Se concentration in these tissues, suggest that Au-Se complexes may have limited the biosynthesis of the enzyme. Au affects Se distribution, and Se concentrates Au in tissues with a high lysosomal content.

While the term "drug-nutrient interactions" tends to conjure up a concept of an adverse combination, such as anticonvulsants impairing folate metabolism or alcohol blocking active thiamine absorption, there are situations in which a drug and nutrient can act in a complementary manner, to correct a metabolic defect. This case history illustrates such a positive interaction of glucocorticoids and L-carnitine supplements improving muscle function in a patient with myopathic carnitine deficiency.

The single-dose kinetics of the psychotropic phenothiazine dixyrazine was assessed in eight young healthy volunteers given the drug at three occasions: 10 mg intravenously, 25 mg orally in the fasting state, and 25 mg orally together with a standardized breakfast of 1,840 kJ. The plasma concentrations of dixyrazine were measured by high-pressure liquid chromatography. Like some other lipophilic weakly basic drugs, dixyrazine showed a rapid disappearance from plasma, having an elimination half-life of 3.4 h, a clearance of about 1,200 ml/min, and an apparent volume of distribution of 5.9 l/kg. Dixyrazine was found to have a very low and interindividually varying bioavailability; in the fasting state, dixyrazine bioavailability was only 1% in one subject, 3-6% in five others, and 11 and 24% in the remaining two subjects. The mean fasting bioavailability was 7.4%. After intake with breakfast, the mean bioavailability was increased to 12.4% (p less than 0.01), with a range of 2-29%. Probably, the low oral bioavailability is due to extensive presystemic (hepatic) degradation, and the food effect to a reduction of this process.

An experimental model of protein energy malnutrition was produced in five young rhesus monkeys and the pharmacokinetics of antipyrine were studied at three points, initially, during protein energy malnutrition and following nutritional rehabilitation. In a separate group of animals, the estimation of hepatic enzyme aminopyrine N-demethylase was performed. There was a significant decrease in the elimination kinetics, the half life was increased, and the clearance rate was decreased in the malnourished animals, which correlated with a corresponding decrease in aminopyrine N-demethylase activity.

Studies were carried out to evaluate the comparative effectiveness of cholestyramine and pectin as hypocholesterolemic agents. Circulating levels of serum cholesterol and lipoprotein-associated cholesterol were measured in rats fed high cholesterol diet supplemented with either cholestyramine or pectin. When compared with controls, a significant decrease in the level of total cholesterol was observed in rats fed either cholestyramine or pectin (p less than 0.001, 43% reduction in cholesterol, and p less than 0.04, 25% reduction in cholesterol, respectively) and this was due exclusively to the lowering of low density lipoprotein. Further statistical evaluation of data revealed no significant difference between the cholesterol levels of rats fed either cholestyramine or pectin (p greater than 0.07). The data acquired in this study suggest that both cholestyramine and pectin are comparable and effective hypocholesterolemic agents and the observed hypocholesterolemic effect of these agents is mediated through lowering of cholesterol associated with the low density lipoprotein.

Syrian golden hamsters fed diets of raw or heated soy flour for 16 months had an incidence (4%) of pancreatic neoplasms in both groups. Animals injected with N-nitrosobis (2-oxopropyl) amine (BOP) and fed heated soy flour for 15 months developed a high incidence (88%) of microscopic benign and malignant neoplasms, primarily of ductal origin. This was in marked contrast to a similar group of BOP-injected animals which had been fed raw soy flour and in which the incidence of pancreatic neoplasms was less than 10%.