Drugs online research references
Klin Wochenschr. 1990 Jul 5;68(13):692-8.
Gemfibrozil absorption and elimination in kidney and liver disease.
Knauf H, Kolle EU, Mutschler E.
Medizinische Klinik I, St. Bernward Krankenhaus, Hildesheim.
The disposition of the lipid-lowering drug gemfibrozil was studied in patients with either renal (n = 8) or hepatic disease (n = 8) and compared to those of healthy volunteers (n = 6). Gemfibrozil was determined in plasma and urine by means of a HPLC method. Urine was also analyzed for gemfibrozil conjugates. Following oral administration of 900 mg gemfibrozil, maximal plasma levels of the parent drug were 46.1 +/- 15.8 micrograms/ml, attained after 2.2 +/- 1.1 h. In chronic renal failure and in liver cirrhosis the plasma concentrations of gemfibrozil did not significantly differ from that of controls except in those patients who were co-medicated with antacids. These patients had significantly lower Cmax and AUC values. The elimination half-life of the drug was 1.5 h in controls, 2.4 h in renal failure, and 2.1 h in liver disease. In healthy volunteers, only 0.02 to 0.15% of the given dose was recovered in the urine as parent gemfibrozil, while conjugates made up 7-14%. In patients with renal failure also, only traces of parent gemfibrozil could be detected, and conjugates accounted for 0.5-9.8%. In those with liver disease, however, about 0.1-0.2% were recovered in urine as parent gemfibrozil and up to 50% as conjugates. Strikingly, the amount of excreted conjugates in the urine was positively correlated to the direct bilirubin plasma concentration.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2381138&dopt=Abstract
Biochem Pharmacol. 1989 Dec 1;38(23):4169-76.
Quantitative assessment of enzyme induction by peroxisome proliferators and application to determination of effects on triglyceride biosynthesis in primary cultures of rat hepatocytes.
Kocarek TA, Feller DR.
Division of Pharmacology, College of Pharmacy, Ohio State University, Columbus 43210.
Potencies for the induction of peroxisomal fatty acyl-CoA oxidase (FACO) and microsomal laurate hydroxylase (LH) were determined for clofibric acid (CPIB), ciprofibrate (Cipro) and gemfibrozil (Gem) in primary cultures of rat hepatocytes based on complete concentration-response analysis and determination of theoretical maximum inductive responses for Cipro. CPIB and Cipro each induced FACO and LH in a concentration-dependent manner. Scatchard analysis of the data allowed calculation of EC50 values (mM) of 0.82 and 0.028 (for FACO) and 0.22 and 0.0081 (for LH) for CPIB and Cipro respectively. The EC50 ratios (CPIB/Cipro) were identical (29-fold) for induction of FACO and LH, supporting the concept that these enzymes are induced by CPIB and Cipro through a common mechanism. By comparison, Gem was relatively ineffective as an inducer of FACO and LH. Furthermore, Gem did not antagonize Cipro-mediated enzyme inductions, suggesting that Gem is a peroxisome proliferator of low potency rather than a partial agonist. Based on the potency and time-course profiles observed for induction of FACO and LH, the effects of CPIB, Cipro and Gem on triglyceride (TG) biosynthesis were determined in the cultured rat hepatocytes. Conditions of maximal FACO and LH induction by the drugs did not result in inhibition of TG biosynthesis in the cells. These results support the in vivo evidence which indicates that FACO and LH induction are not causally linked to the hypotriglyceridemic actions of peroxisome proliferating drugs.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2597188&dopt=Abstract
Exp Gerontol. 1990;25(1):37-46.
Effect of gemfibrozil on erythrocyte membrane lipids in geriatric patients.
Bauer M, Platt D, Hager K.
Institute of Gerontology, University of Erlangen/Nurenberg, Federal Republic of Germany.
Twenty geriatric patients with primary or secondary hyperlipidemia and suffering from various other diseases received for three weeks once daily 900 mg gemfibrozil. The hyperlipidemia had not been treated before, and a cholesterol-reduced diet did not succeed in lowering total cholesterol below 6.75 mmol/l (260 mg/100 ml) and serum triglycerides below 1.97 mmol/l (175 mg/100 ml). The purpose of this study was to analyze the lipid composition of the erythrocyte membrane, serum lipids and rheological parameters before and after the therapy. Mean serum total cholesterol and triglyceride content decreased significantly by 16.3% (p less than 0.05) and 35.2% (p less than 0.01) on average, respectively. Aggregation of thrombocytes and of erythrocytes, thrombin time and partial thromboplastin time slightly varied during the three weeks' treatment, but without statistical significance. The content of total long-chain saturated fatty acids in the phospholipid fraction of the erythrocyte membrane decreased slightly from 41.3% to 40.9% (p less than 0.05), whereas the total w6-unsaturated fatty acids without the precursor linoleic acid increased by about the same extent from 15.66% to 16.0% (p less than 0.05). The molar ratio of phospholipid to cholesterol content decreased significantly (p less than 0.01) due to a reduced phospholipid content at the end of the therapy. In conclusion, in addition to reducing the serum lipids, gemfibrozil slightly effects the lipid composition of erythrocytes, but the effects of the varied concentrations of long-chain saturated and long-chain w6-unsaturated fatty acids in the phospholipid fraction on membrane fluidity might be compensated, at least partly, by the decrease of the ratio of membrane phospholipid to cholesterol.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2318281&dopt=Abstract
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