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Arzneimittelforschung. 1985;35(11):1637-9.
Determination of gemfibrozil in plasma by high performance liquid chromatography.

Hengy H, Kolle EU.

A sensitive and specific method for the determination of 5-(2,5-dimethylphenoxy)-2,2-dimethyl-pentanoic acid (gemfibrozil, Gevilon) at therapeutic concentrations in plasma is described. The method is based on high performance liquid chromatography and the use of ibuprofen as internal standard. Gemfibrozil and the internal standard are extracted from acidified plasma into cyclohexane and the resulting residue is analyzed on a commercial reversed phase column with acetonitrile/water 1:1 and 0.2% phosphoric acid as mobile phase. The eluted peaks are detected by UV-absorption at 225 nm. The sensitivity is approx. 50 ng/ml plasma using a 0.5-ml sample. The applicability to pharmacokinetic studies of gemfibrozil is demonstrated.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3867353&dopt=Abstract




J Biol Chem. 1983 Mar 10;258(5):3090-3.
The rapid induction of liver glycerophosphate acyltransferase in mice by clofibrate, a hypolipidemic agent.

Das AK, Aquilina JW, Hajra AK.

Administration of clofibrate to adult mice (20-25 mg of clofibrate/day) increased liver glycerophosphate acyltransferase (EC 2.3.1.15) activity by 2.3-fold within 24 h. This increased glycerophosphate acyltransferase activity was mainly localized in the liver microsomal fraction. Three other hypolipidemic drugs, i.e. Bezafibrate (Boehringer Mannheim Co.), Gemfibrozil (Warner-Lambert Co.) and Wy-14,643 (Wyeth Laboratories), when fed to mice, also increased the liver glycerophosphate acyltransferase activity by 2-3-fold in 24 h. Simultaneous administration of inhibitors of protein biosynthesis, such as cycloheximide or actinomycin D completely abolished such stimulation of liver glycerophosphate acyltransferase by clofibrate.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6826552&dopt=Abstract




Circulation. 1995 Aug 15;92(4):767-72.
Attenuation of the synthesis of plasminogen activator inhibitor type 1 by niacin. A potential link between lipid lowering and fibrinolysis.

Brown SL, Sobel BE, Fujii S.

Cardiovascular Division, Washington University School of Medicine, St Louis, Mo, USA.

BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1), the primary physiological inhibitor of endogenous plasminogen activators, has been implicated as a potentiating factor in atherogenesis as well as in coronary thrombosis. We and others have observed attenuation of PAI-1 expression by gemfibrozil both in vivo and in vitro. METHODS AND RESULTS: To determine whether other lipid-lowering agents with different mechanisms of action exert similar effects, we exposed Hep G2 cells, a highly differentiated human hepatoma cell line, to selected concentrations of niacin. Accumulation of PAI-1 protein, assayed with an ELISA, decreased in conditioned media by 72% in 48 hours in a specific, concentration-dependent fashion. Metabolic labeling experiments demonstrated a decrease in the rate of PAI-1 synthesis. Northern blot analysis demonstrated a preceding, parallel, and specific decrease in the concentration of PAI-1 mRNA. Niacin attenuated the increased PAI-1 synthesis induced by mediators released from thrombi as well. Thus, with 4.25 ng/mL transforming growth factor-beta 1, PAI-1 accumulation increased 4.5-fold in conditioned media in 48 hours. However, niacin attenuated the increase by 65%. Again, both the rate of PAI-1 synthesis and PAI-1 mRNA were reduced. The increased plasma PAI-1 activity and PAI-1 mRNA in liver induced by dexamethasone (0.8 mg IP) in vivo in rats were attenuated by 3 weeks of pretreatment with niacin. CONCLUSIONS: These results suggest that niacin, by decreasing PAI-1 expression, may potentiate fibrinolysis, thereby decreasing the stimulation of atherogenesis by clot-associated mitogens associated with microthrombi. Furthermore, the results imply that a pathogenetic link may exist between intracellular lipid metabolism and regulation of expression of fibrinolytic system components.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7641354&dopt=Abstract













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