Drugs online research references
Angiology. 2002 May-Jun;53(3):273-7.
Effect of ciprofibrate on C-reactive protein and fibrinogen levels.
Rizos E, Kostoula A, Elisaf M, Mikhailidis DP.
Department of Internal Medicine, Medical School, University of Ioannina, Greece.
Statins can lower the circulating levels of C reactive protein (CRP). This effect may be relevant because CRP is a predictor of vascular risk. In contrast, the evidence that fibrates lower CRP levels is very limited. The effect of treatment with ciprofibrate (100 mg once daily) was investigated for 8 weeks in 30 patients with primary dyslipidemia. There was a significant (p < 0.01) decrease in median (range) CRP levels by 36.8% from 1.9 mg/L (1.0-6.0 mg/L) to 1.2 mg/L (1.0-5.5 mg/L). Plasma fibrinogen levels were also significantly (p = 0.05) reduced. There was no correlation between the fall in CRP levels and the changes in lipid or fibrinogen levels. These findings support the concept that fibrates, like the statins, lower serum CRP levels. However, fibrates have a different mode of action. Fibrates (with the exception of gemfibrozil) also consistently lower plasma fibrinogen levels. In contrast, the effect of statins on the circulating levels of this coagulation factor remains to be defined. These differences may help in defining the mechanisms responsible for drug-induced changes in the circulating levels of CRP and fibrinogen. A favorable effect on CRP and fibrinogen levels may increase the clinical efficacy of statins and fibrates.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12025914&dopt=Abstract
J Chromatogr A. 2002 Apr 5;952(1-2):139-47.
Analysis of acidic drugs in the effluents of sewage treatment plants using liquid chromatography-electrospray ionization tandem mass spectrometry.
Miao XS, Koenig BG, Metcalfe CD.
Water Quality Centre, Trent University, Peterborough, Ont., Canada.
A liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS-MS) method was developed and validated for simultaneous analysis of nine acidic pharmaceutical drugs (bezafibrate, clofibric acid, diclofenac, fenoprofen, gemfibrozil, ibuprofen, indomethacin, ketoprofen and naproxen) in sewage treatment plant (STP) effluents. The mean recoveries of the pharmaceuticals ranged from 58.9 to 91.5% in STP effluent, and the limits of detection of the analytes were 5-20 ng/ml. The method was applied to the quantitative analysis of acidic drugs in the effluents from three Canadian STPs, in which bezafibrate, diclofenac, fenoprofen, gemfibrozil, ibuprofen, indomethacin and naproxen were detected.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12064526&dopt=Abstract
J Pharmacol Exp Ther. 2002 Jul;302(1):43-9.
Effect of albumin and cytosol on enzyme kinetics of tolbutamide hydroxylation and on inhibition of CYP2C9 by gemfibrozil in human liver microsomes.
Wang JS, Wen X, Backman JT, Neuvonen PJ.
Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Haartmaninkatu 4, FIN-00290 Helsinki, Finland.
The effect of human serum albumin (Hsa) and human liver cytosol (Hlc) on the in vitro enzyme kinetics of the formation of hydroxytolbutamide (CYP2C9 marker reaction) and the inhibitory effect of gemfibrozil on tolbutamide hydroxylation were examined using human liver microsomes. The addition of Hsa greatly decreased the unbound concentrations of tolbutamide and gemfibrozil in the incubation medium, whereas Hlc only slightly decreased them. The unbound K(m) value for tolbutamide hydroxylation was 123 microM without Hsa and Hlc, and 73, 88, and 64 microM in the presence of Hsa (5 mg/ml), Hlc (0.5 mg/ml), and Hsa plus Hlc, respectively. The predicted in vivo hepatic clearance (CL(h)) of tolbutamide based on enzyme kinetics without Hsa and Hlc (0.06 ml/min/kg) was 40% of its in vivo clearance (0.15 ml/min/kg) based on published data. Addition of 5 mg/ml Hsa and 0.5 mg/ml Hlc to the incubation medium distinctly improved the prediction, with the coaddition of Hsa and Hlc yielding the most accurate value (0.14 ml/min/kg). The K(i) (6 microM) of gemfibrozil for CYP2C9, calculated using total drug concentrations, was increased by Hlc (8 microM), Hsa (40 microM), or both (72 microM). However, when the unbound substrate and inhibitor concentrations were considered, the K(i) (6 microM without Hsa and Hlc) was not markedly altered by Hsa (4 microM), Hlc (8 microM), or both Hsa and Hlc (9 microM). The present findings suggest that the addition of Hsa and Hlc to microsomal incubation media may yield enzyme kinetic estimates more comparable with in vivo results.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12065698&dopt=Abstract
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