Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PPARalpha agonists have been characterized largely in terms of their effects on lipids and glucose metabolism, whereas little has been reported about effects on amino acid metabolism. We studied responses to the PPARalpha agonist WY 14,643 (30 micromol x kg(-1) x day(-1) for 4 wk) in rats fed a saturated fat diet. Plasma and urine were analyzed with proton NMR. Plasma amino acids were measured using HPLC, and hepatic gene expression was assessed with DNA arrays. The high-fat diet elevated plasma levels of insulin and triglycerides (TG), and WY 14,643 treatment ameliorated this insulin resistance and dyslipidemia, lowering plasma insulin and TG levels. In addition, treatment decreased body weight gain, without altering cumulative food intake, and increased liver mass. WY 14,643 increased plasma levels of 12 of 22 amino acids, including glucogenic and some ketogenic amino acids, whereas arginine was significantly decreased. There was no alteration in branched-chain amino acid levels. Compared with the fat-fed control animals, WY 14,643-treated animals had raised plasma urea and ammonia levels as well as raised urine levels of N-methylnicotinamide and dimethylglycine. WY 14,643 induced changes in a number of key genes involved in amino acid metabolism in addition to expected effects on hepatic genes involved in lipid catabolism and ketone body formation. In conclusion, the present results suggest that, in rodents, effects of pharmacological PPARalpha activation extend beyond control of lipid metabolism to include important effects on whole body amino acid mobilization and hepatic amino acid metabolism.
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PMID:Beyond lipids, pharmacological PPARalpha activation has important effects on amino acid metabolism as studied in the rat. 1716 30

Lovastatin and extended-release (ER) niacin in a fixed dose combination (Advicor) is approved for the treatment of dyslipidemia. Since both drugs are extensively metabolized, this study investigated the bioavailability and pharmacokinetics of their co-administration following single-dose administration. In a 4-way crossover study 40 subjects received: two 1000/20 Advicor tablets (ADV), two 1000 mg niacin ER tablets (NSP), two 20mg lovastatin tablets (Mevacor; MEV), and two niacin ER 1000 mg tablets with two lovastatin 20mg tablets (NSP+MEV). Plasma was assayed for niacin, nicotinuric acid (NUA), lovastatin, lovastatin acid and HMGCoA reductase inhibition. Urine was assayed for niacin and its metabolites, NUA, N-methylnicotinamide and N-methyl-2pyridone-5-carboxamide. Least square mean ratios and 90% confidence intervals for C(max) and AUC((0-t)) were determined for NSP+MEV versus MEV or NSP, ADV versus MEV or NSP, and ADV versus NSP+MEV. Co-administration of niacin and lovastatin did not significantly influence C(max) and AUC((0-t)) of lovastatin, niacin, NUA and total urinary recovery of niacin and metabolites. A 22 to 25% decrease in lovastatin acid C(max) was observed while lovastatin acid AUC((0-t)) was not affected. The HMGCoA reductase inhibition C(max) and AUC((0-t)) were not affected indicating that the difference in lovastatin acid C(max) was not clinically relevant.
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PMID:The comparative bioavailability of an extended-release niacin and lovastatin fixed dose combination tablet versus extended-release niacin tablet, lovastatin tablet and a combination of extended-release niacin tablet and lovastatin tablet. 1757 Dec 83