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The time course of radioactivity in plasma and the excretion in urine and faeces over 7 days were determined in 12 healthy subjects after single oral and intravenous doses of a solution ofH-β-methyldigoxin. 62.2±2.1 and 29.0±5.2 per cent of the dose were excreted in urine and faeces, respectively, within 7 days of intravenous administration, compared with 55.2±2.8 and 28.6±5.7 per cent after oral administration. This indicates almost complete absorption of the glycoside when given in solution. 12 hours after its administration a pseudo-distribution equilibrium was reached and the average half life of tritiated compounds was 1.3 days. By 48 - 96 hours after treatment the average half life was 2.8 days. O-demethylation was revealed as the main metabolic degradation step in man. The rate of Demethylation was higher after oral than i.v. administration. Thus, only 31% of the radioactivity excreted in the urine consisted of unchanged β-methyldigoxin after oral administration compared to 51% after i.v. dosing. Only traces of bis- and monoglycosides were excreted in urine, but there were considerable amounts in faeces, where they accounted for more than 35% of the total excretion. Up to 40% of the radioactivity in plasma and urine consisted of polar conjugates during the first 12 hours after administration of β-methyldigoxin. The mono- and bisglycosides were identified as the main products of conjugation. During the 7 days approximately 15% of the administered dose was metabolized by splitting off glycosidic bonds and conjugation to polar compounds. [ABSTRACT FROM AUTHOR]

Objectives: The HMG-CoA reductase inhibitors, or statins, are well established in the prevention and treatment of coronary artery disease, mainly by lowering low-density lipoprotein (LDL) cholesterol levels. These compounds are structurally similar, but differ in their lipophilicity. Several studies have indicated a link between cholesterol and Alzheimer's disease (AD), and there is also epidemiological evidence that statin treatment may decrease the prevalence of dementias. In the present study we wanted to investigate whether pravastatin treatment affects brain cholesterol metabolism., Methods: A post hoc analysis was performed with plasma material from a clinical trial where 51 healthy men (35+/-4 years) were randomly assigned to receive either pravastatin (40 mg/day) or placebo for 6 months. Cholesterol, its precursor lathosterol, its brain-specific metabolite 24(S)-hydroxycholesterol (24S-OH-chol) and 27-hydroxycholesterol (27-OH-chol) were determined in plasma samples before and after treatment by using gas-liquid chromatography (GC)-flame ionization detection (GC-FID) and GC mass spectrometry (GC-MS)., Results: Besides reducing total cholesterol (-20%, P<0.001) and LDL cholesterol (LDL-C; -33%, P<0.001) concentrations, pravastatin treatment resulted in a decrease of the ratio of lathosterol to cholesterol, a surrogate marker of endogenous cholesterol synthesis, by 20% (P<0.05). Absolute concentrations of 24S-OH-chol were not altered, but its ratio to cholesterol slightly increased by 15% (P<0.05). 27-OH-chol concentrations as well as its ratio to cholesterol were both significantly altered due to pravastatin treatment (-7% and +14%, P<0.05 for both, respectively)., Conclusions: The treatment with pravastatin 40 mg once a day for 6 months does not affect brain cholesterol metabolism as judged by plasma concentrations of 24(S)-hydroxycholesterol.

Objective: 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors have been suggested as agents to reduce the biliary cholesterol saturation index (CSI) in duodenal bile and therefore might be supportive in primary or secondary prevention of gallstones. However, the efficiency of the therapy seems to depend on both the HMG-CoA reductase inhibitor used and the study population selected., Methods: We therefore investigated the effect of a high-dose application of fluvastatin on biliary lipid composition in 21 subjects exhibiting mild hypercholesterolaemia and a history of current gallstones or cholecystectomy due to gallstone disease. Subjects were treated either with 40 mg fluvastatin twice per day over a 3-month period (n = 14) or with placebo (n = 7). Bile samples were aspirated during endoscopy after intravenous ceruletid stimulation before and after therapy., Results: Both groups were comparable in CSI (mean +/- SD) at baseline (1.78 +/- 0.2 placebo vs. 1.97 +/- 0.4 verum). CSI significantly decreased in the verum group to 1.45 +/- 0.4 (P = 0.003) mainly due to increased phospholipid levels, whereas no difference was observed in the placebo group (1.85 +/- 0.7, n.s.). In addition, the verum group exhibited a significant reduction of hydrophobic deoxycholic acid, which has been reported to induce cholesterol crystal precipitation, and an increase of hydrophilic cholic acid., Conclusion: Fluvastatin might decrease the risk of cholesterol gallstone formation in patients with elevated biliary CSI during long-term treatment by reduction of biliary cholesterol saturation and percentage change in deoxycholic acid content.