Drugs online research references
Arterioscler Thromb Vasc Biol. 1995 Aug;15(8):1064-9.
Effects of different phenotypes of hyperlipoproteinemia and of treatment with fibric acid derivatives on the rates of cholesterol 7 alpha-hydroxylation in humans.
Bertolotti M, Concari M, Loria P, Abate N, Pinetti A, Guicciardi ME, Carulli N.
Department of Internal Medicine, University of Modena, Italy.
Little is known about the relationships between hyperlipidemia and bile acid metabolism. However, hypolipidemic treatment with fibric acid derivatives has been shown to increase biliary cholesterol secretion, presumably by reducing bile acid synthesis. To clarify such relationships, we investigated the effects of different hyperlipoproteinemic conditions and of treatment with fibric acid derivatives on the rates of cholesterol 7 alpha-hydroxylation (the limiting step of bile acid synthesis) in humans. We studied 10 patients (aged 36 to 68 years) with lipoprotein phenotype IIa and with a clinical diagnosis of heterozygous familial hypercholesterolemia, a condition of reduced activity of LDL receptors, and 11 patients (aged 48 to 70 years) with lipoprotein phenotype IIb or IV and clinical diagnosis of familial combined hyperlipidemia, a condition probably related to increased hepatic lipoprotein synthesis. Cholesterol 7 alpha-hydroxylation rates were assayed in vivo by tritium release assay after an intravenous injection of [7 alpha-3H]cholesterol. The results were compared by ANOVA to the values obtained in a group of 28 normolipidemic patients (aged 34 to 83 years), with age as the covariate. Six patients were also studied after treatment with gemfibrozil (900 to 1200 mg/d for 6 to 8 weeks) and 5 patients were studied after treatment with bezafibrate (400 mg/d for 6 to 8 weeks). Hydroxylation rates were 0.82 +/- 0.22 mmol/d in the familial hypercholesterolemia group and 1.30 +/- 0.47 mmol/d in the familial combined hyperlipidemia group (P < .05 between the two groups and between patients with familial combined hyperlipidemia and control subjects; P = NS between patients with familial hypercholesterolemia and control subjects, as determined by ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7627697&dopt=Abstract
J Med Chem. 1983 Jul;26(7):1020-7.
Phenylenebis(oxy)bis[2,2-dimethylpentanoic acid]s: agents that elevate high-density lipoproteins.
Sircar I, Hoefle M, Maxwell RE.
A series of phenylenebis(oxy)bis[2,2-dimethylpentanoic acid]s have been synthesized and evaluated as potential hypolipidemic agents. Compound 18 (CI-924) was found to be the most potent compound in this series. In rats, compound 18 not only reduced low-density lipoprotein cholesterol but also increased high-density lipoprotein (HDL) cholesterol. Comparative studies in rats indicated 18 produced an equal elevation of HDL cholesterol at one-third of the dose required of gemfibrozil. Structure-activity relationships are discussed.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6864730&dopt=Abstract
Pharmazie. 1993 Dec;48(12):900-4.
Photolability and photohemolytic studies of fibrates.
Vargas F, Canudas N.
Centro de Quimica, Instituto Venezolano de Investigationes Cientificas (IVIC), Caracas.
Fenofibrate (1), gemfibrozil (2), clofibric acid (3), benzafibrate (4) and clofibrate (5) were found to be photolabile by UV-B (290-320 nm) light under aerobic conditions. The drugs 1, 2, 3 and 4 were phototoxic in vitro when examined by the photohemolysis test both under oxygen and argon atmosphere, although the photohemolysis rate was markedly lower under anaerobic conditions. Based on the inhibition of this process upon addition of butylated hydroxyanisole (BHA) and reduced glutathione (GSH), a radical chain (type I) mechanism appears to operate. Inhibition was seen in the presence of sodium azide (NaN3) and 1,4-diazabicyclo[2.2.2]octane (DABCO) as also in D2O induced-photohemolysis. No photohemolysis was evident for clofibrate (5) under these conditions. In summary, fenofibrate, gemfibrozil, clofibric acid and bezafribrate are phototoxic in vitro. This behavior can be explained through the involvement of free radicals, singlet oxygen and stable photoproducts.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8115436&dopt=Abstract
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