Drugs online research references
J Clin Pharmacol. 1987 Dec;27(12):994-1000.
The effect of renal function on the pharmacokinetics of gemfibrozil.
Evans JR, Forland SC, Cutler RE.
Department of Medicine, Loma Linda University Medical Center, Jerry L. Pettis Memorial Veterans Hospital, CA 92357.
Study objective: to determine the effect of renal function on the pharmacokinetics of gemfibrozil following single and multiple oral doses. Design: nonrandomized; paired studies of single versus multiple doses. Setting: patients enrolled in a veterans hospital renal subspecialty clinic. Patients: 17 male patients 57 to 74 years old selected for various levels of renal function, including end-stage renal disease. Interventions: patients initially received 600 mg of oral-gemfibrozil followed by sequential venous blood sampling. Seven to 14 days later, the patients started receiving gemfibrozil, 600 mg bid. Venous blood samples were obtained over the following 10 days and frequently during a 24-hour washout phase. Measurements and main results: peak gemfibrozil concentrations (mg/L) were 11.1 (3.9 SD) for the single dose and 10.2 (3.8) for the multiple-dose study. Time to peak concentration (hr) was 2.1 (1.0) and 1.8 (0.6), respectively. The mean half-life of elimination (hr) from the single-dose study was 6.4 (11.8) compared with the multidose study of 3.0 (3.1), which did not reach statistical significance (P = .25). The difference between the area under the curve for the single versus the multiple-dose study approached statistical significance (P = .054). The coefficient of determination for creatinine renal clearance versus the plasma clearance of oral gemfibrozil was 0.009 (P = .72) for the single-dose regimen and 0.331 (P = .016) for the multiple-dose study. Conclusion: the half-life of gemfibrozil is independent of renal function for both single- and multiple-dose regimens. Dosing schedules do not require alteration for renal insufficiency.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3481387&dopt=Abstract
Metabolism. 1993 Nov;42(11):1486-91.
Effect of gemfibrozil on adipose tissue and muscle lipoprotein lipase.
Simsolo RB, Ong JM, Kern PA.
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
To better understand the mechanism of action of gemfibrozil on plasma triglycerides, lipoprotein lipase (LPL) concentration was measured in adipose tissue and muscle of 16 hypertriglyceridemic patients before and after treatment with gemfibrozil for 6 weeks. The patients were divided into three groups based on clinical criteria as follows: group 1, hypertriglyceridemia without secondary factors; group 2, hypertriglyceridemia with diabetes; and group 3, hypertriglyceridemia with renal insufficiency. LPL activity, immunoreactive mass, synthetic rate, and mRNA levels were measured in the adipose tissue samples, and LPL activity and mass in the muscle samples. Serum triglyceride levels were decreased by 46% by gemfibrozil, and patients demonstrated no change in diet, weight, or glycohemoglobin during the 6 weeks of treatment. Despite the decrease of blood triglyceride levels, there was no significant change in any measure of LPL either in adipose tissue or muscle. Although several patients demonstrated increases in muscle LPL activity, these changes were inconsistent and not statistically significant. Because there was no significant change in LPL, we conclude that gemfibrozil in these patients decreased circulating triglyceride levels predominantly by decreasing hepatic very-low-density lipoprotein (VLDL) secretion.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8231846&dopt=Abstract
Am J Med. 1987 Nov 27;83(5B):85-9.
Potential use of fenofibrate and other fibric acid derivatives in the clinic.
Brown WV.
Department of Medicine, Mt. Sinai Hospital, New York, New York.
The fibric acid derivatives continue to have a place in the treatment of hyperlipidemia. The third generation of these drugs, including fenofibrate, appears to offer some advantages over those currently available in the United States. These drugs should be prescribed only after dietary and lifestyle changes have been offered as the preferable treatment. In severe hypertriglyceridemia, clofibrate, gemfibrozil, or fenofibrate may reduce the very low-density lipoprotein and chylomicron levels adequately. Dysbetalipoproteinemia may also be completely controlled by a combination of diet and any one of these drugs. When the low-density lipoprotein level is elevated, the newer fibric acid derivatives, such as fenofibrate, may be more effective in lowering the plasma cholesterol levels. This is true for those patients with elevated low-density lipoprotein and normal very low-density lipoprotein triglyceride levels, as well as those with elevated very low-density lipoprotein triglyceride levels. A 20 percent reduction in low-density lipoprotein cholesterol levels is expected when the triglyceride levels are not elevated. When the very low-density lipoprotein triglyceride levels are elevated, the low-density lipoprotein response is more variable, and on occasion the low-density lipoprotein cholesterol level may rise as the very low-density lipoprotein level is reduced. The average reduction in low-density lipoprotein cholesterol levels (about 6 percent) caused by fenofibrate may be greater in patients with elevated very low-density lipoprotein triglyceride levels than by other fibrates. In combination with other agents that lower low-density lipoprotein levels more specifically, such as the bile acid sequestrants and hydroxymethylglutaryl coenzyme A reductase inhibitors, fenofibrate may act to effect control of the triglycerides allowing management of those patients with disorders producing elevated very low-density lipoprotein and low-density lipoprotein levels. Extensive European experience with fenofibrate (six million patient-years) indicates that severe side effects are unlikely. However, the physician should monitor patients for skin rash, liver and renal function abnormalities, gastrointestinal dysfunction, and generalized muscle tenderness. All of these usually appear very early in the course of treatment and are reversible. Of greater concern is the possibility of an increased incidence of cholelithiasis, since the bile becomes relatively enriched in cholesterol during therapy with any fibric acid derivative.(ABSTRACT TRUNCATED AT 400 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3688012&dopt=Abstract
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