digoxin and Hyperlipidemias

Drug-drug interactions (DDIs) are a well known risk factor for adverse drug reactions. HMG-CoA reductase inhibitors ('statins') are a cornerstone in the treatment of dyslipidaemia and patients with dyslipidaemia are concomitantly treated with a variety of additional drugs. Since DDIs are associated with adverse reactions, we performed a cross-sectional study to assess the prevalence of potentially critical drug-drug and drug-statin interactions in an outpatient adult population with dyslipidaemia.. Data from patients with dyslipidaemia treated with a statin were collected from 242 practitioners from different parts of Switzerland. The medication list was screened for potentially harmful DDIs with statins or other drugs using an interactive electronic drug interaction program.. We included 2742 ambulatory statin-treated patients (mean age +/- SD 65.1 +/- 11.1 years; 61.6% males) with (mean +/- SD) 3.2 +/- 1.6 diagnoses and 4.9 +/- 2.4 drugs prescribed. Of those, 190 patients (6.9%) had a total of 198 potentially harmful drug-statin interactions. Interacting drugs were fibrates or nicotinic acid (9.5% of patients with drug-statin interactions), cytochrome P450 (CYP) 3A4 inhibitors (70.5%), digoxin (22.6%) or ciclosporin (cyclosporine) [1.6%]. The proportion of patients with a potential drug-statin interaction was 12.1% for simvastatin, 10.0% for atorvastatin, 3.8% for fluvastatin and 0.3% for pravastatin. Additionally, the program identified 393 potentially critical non-statin DDIs in 288 patients.. CYP3A4 inhibitors are the most frequent cause of potential drug interactions with statins. As the risk for developing rhabdomyolysis is increased in patients with drug-statin interactions, clinicians should be aware of the most frequently observed drug-statin interactions and how these interactions can be avoided.

Topics: Aged; Ambulatory Care; Aryl Hydrocarbon Hydroxylases; Atorvastatin; Comorbidity; Cross-Sectional Studies; Cyclosporine; Cytochrome P-450 CYP3A; Digoxin; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Male; Niacin; Oxidoreductases, N-Demethylating; Physicians; Pravastatin; Prevalence; Product Surveillance, Postmarketing; Pyrroles; Simvastatin; Time Factors

Our object was to evaluate the effects of regular mild exercise on blood pressure and on circulating level of ouabainlike factors (OLF) and of nitrate anion, an endproduct of nitric oxide (NO) in humans. We measured plasma ouabainlike immunoreactivity (OLI) and nitrate ions (NO3.) before and after mild exercise for 3 months' duration in 16 patients with essential hypertension, diabetes mellitus, obesity, or hyperlipidemia. Plasma OLI was measured using an amplified ELISA system with anti-ouabain antibody and biotinyl-tyramide. Serum NO3. was measured with high-performance liquid chromatography (HPLC) with an anion-exchange column. With the reverse phase HPLC system with an octa decylsilyl silicagel column, the elution volume of plasma OLI of a healthy volunteer matched that of authentic ouabain in a gradient elution system of acetonitrile/H2O. Plasma OLI levels decreased significantly by about 34% after mild exercise, and NO3. levels tended to be within the reference interval in normal volunteers. Body weight, diastolic and systolic blood pressure, serum triglyceride and acetylcholine esterase (a marker of the fatty liver) were significantly decreased (p < 0.01) after 3 months of regular mild exercise. The plasma OLI level was significantly correlated with plasma NO3., there was a trend toward a correlation with diastolic blood pressure (p = 0.06) before and after regular exercise. Regular mild exercise led to a decrease in plasma levels of OLI, and acetylcholine esterase activity and blood pressure in adult patients. Results suggest that changes in OLF production contribute to the blood pressure regulation seen in patients who exercise regularly.

Topics: Adult; Aged; Blood Pressure; Cardenolides; Chromatography, High Pressure Liquid; Diabetes Mellitus; Digoxin; Enzyme-Linked Immunosorbent Assay; Exercise; Female; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Nitrates; Nitric Oxide; Obesity; Ouabain; Saponins

The study was carried out on 18 male rabbits randomaly ascribed into two groups: control one on standard diet and experimental one on high-fat diet for 2 months. Pharmacokinetic assays were performed in all animals after 2 months of the experiment. Blood was sampled within 24 hours after intragastrical administration of digoxin at a dose 0.02 mg/kg. The two compartment open model for extravascular administration was used for calculations. Marked increase in plasma drug concentration, as well as decrease in total clearance were noted. The study revealed the influence of experimental hyperlipidemia on digoxin pharmacokinetics leading to a slower drug elimination.

Topics: Animals; Digoxin; Hyperlipidemias; Male; Rabbits

Compliance with medication has a decisive influence on the findings in clinical intervention studies, so the reliable estimation of compliance is vital to the success of such research. This report describes the main findings about compliance in the Helsinki Heart Study, a five-year, double-blind, primary prevention trial of gemfibrozil as a lipid-lowering agent compared with placebo, in 4,081 dyslipidaemic middle-aged men. Three estimation methods were employed: capsule counting at every three-month follow-up visit, urine gemfibrozil analysis at six-month intervals, and, a novel technique, a digoxin marker added to both gemfibrozil and placebo capsules at the end of the third and fifth study years. The estimates of compliance for the study population as a whole generated by these three methods are discussed here. The mean daily capsule count showed that 36% of patients on gemfibrozil men and 39% of those on placebo took more than 90% of their capsules, while only 5% of both groups consumed half or less of the prescribed treatment. According to urinary gemfibrozil analysis, 30% of gemfibrozil subjects had more than 90% positive results and 28% had half or fewer positive. Among study completers, there were 42% gemfibrozil subjects and 50% placebo subjects who on both occasions had the good result in the digoxin marker analysis, while 14% of the gemfibrozil men and 12% of the placebo men scored 'poor' in both marker analyses. Capsule counting revealed a slight deterioration in compliance over the trial period, which was confirmed by the other two methods; for example, the proportion of positive results in the semiannual urine gemfibrozil analyses decreased from 76% to 65%. Medication compliance was slightly better in the placebo group according to capsule counting and digoxin marker methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Capsules; Creatinine; Digoxin; Female; Gemfibrozil; Humans; Hyperlipidemias; Male; Patient Compliance; Randomized Controlled Trials as Topic

Topics: Animals; Dietary Fats; Digoxin; Female; Hyperlipidemias; Male; Rabbits

17 patients on maintenance hemodialysis were monitored for cardiac arrhythmias using ambulatory electrocardiographic recording. Atrioventricular dissociation was found in a patient with an elevated serum digoxin concentration, intradialytic supraventricular tachycardia had been present in a second patient during acute uremic pericarditis prior to the study. Ventricular premature beats (VPB) were absent or of low grade (occasional/uniform) in 14 patients and did not increase on dialysis. 3 patients had potentially dangerous VPB of higher grades (multiform, salvos or R on T) which occurred on or after dialysis in 2. 2 of these 3 patients were overdigitalized, and 2 had severe cardiac disease (amyloid, old myocardial infarction). Several other risk factors (age, hypertension, cardiac hypertrophy, smoking, hyperlipidemia, electrolyte changes) did not seem to be of importance for VPB. In these patients on maintenance hemodialysis, potentially dangerous VPB were rare and occurred mainly during or after dialysis in patients with preexisting heart disease and/or digitalization.

Topics: Arrhythmias, Cardiac; Chronic Disease; Digoxin; Electrocardiography; Female; Glomerulonephritis; Humans; Hyperlipidemias; Hypertension; Kidney Diseases; Male; Middle Aged; Phenacetin; Polycystic Kidney Diseases; Renal Dialysis; Risk

Topics: Calcium; Digoxin; Humans; Hydrocortisone; Hyperlipidemias; Ultracentrifugation

We describe the application of the microencapsulated-antibody technique to the radioimmunoassay of digoxin in serum. Droplets of emulsified rabbit antibody are microencapsulated in a semipermeable nylon membrane by an interfacial polymerization technique. The antibody microcapsules are incubated with 125I-labeled digoxin and unlabeled digoxin for 15 min at 37 degrees C, then free and bound digoxin are separated by centrifugation. Subtherapeutic, therapeutic, and toxic concentrations of digoxin in sera can be determined, with use of a standard curve prepared by use of known amounts of digoxin. With this technique we obtained an intra-laboratory correlation coefficient of 0.945 for 100 patients' sera and one of 0.940 for interlaboratory results for 21 sera (10 laboratories) when compared to a routine clinical laboratory radioimmunoassay for digoxin. Icterus, lipemia, hemoglobin, or disproteinemia had no effect on the analytical recovery of digoxin. The standard curve was linear to 6 microgram/L; the sensitivity was 0.25 microgram/L.

Topics: Antibodies; Bilirubin; Digoxin; gamma-Globulins; Hemolysis; Humans; Hyperlipidemias; Membranes, Artificial; Radioimmunoassay; Triglycerides

We applied the Enzyme Multiplied Immunoassay Technique (EMIT; Syva Corp., Palo Alto, CA) for determination of serum digoxin to the ABA-100 bichromatic analyzer. Assay conditions were almost exactly as prescribed for the manual procedure, but the ABA-100 offers high automation, smaller reagent volumes, and shorter reaction time. Precision studies gave CV's of less than 10%. Sixty patients' samples, analyzed for digoxin by radioimmunoassay and this enzyme immunoassay, gave a correlation (r) of 0.941. Results obtained with the ABA-100 were apparently slightly higher. One kit provides reagents for 250 assays, as compared to 70 assays with the manual procedure. In an emergency situation a result will be available about 60 min after the patient's sample is received; one operator can analyze about 120 samples in 8 h.

Topics: Digoxin; Hemolysis; Humans; Hyperlipidemias; Immunoenzyme Techniques; Jaundice; Radioimmunoassay; Reagent Kits, Diagnostic

The results of parallel determinations of digoxin in the sera of non selected patients (n = 104) by enzyme immunoassay (EMIT-EIA) and radioimmunoassay (J-125 labeled RIA) were compared with each other. The determinations revealed considerably different concentrations; the values determined by EIA were statistical lower (for EIA 1.09 +/- 0.99 ng/ml, for RIA 1.34 +/- 1.01 ng/ml, p less than 0.01). In sera with hemolysis and in sera of patients with hyperlipidemia and uremia false-negative results were found by EIA. After elimination of these sera an exact concordation of the values of both the methods was obtained (for EIA 1.12 +/- 1.01 ng/ml, for RIA 1.12 +/- 1.02 ng/ml, r = 0.95).

Topics: Digoxin; False Negative Reactions; Glucosephosphate Dehydrogenase; Hemolysis; Humans; Hyperlipidemias; Immunoenzyme Techniques; Radioimmunoassay; Uremia

Topics: Adult; Aldosterone; Animals; Biological Transport; Caprylates; Centrifugation; Chickens; Cholesterol; Dicumarol; Digitoxin; Digoxin; Estradiol; Fatty Acids; Hormones; Humans; Hydrocortisone; Hyperlipidemias; Male; Pentobarbital; Pharmaceutical Preparations; Phenytoin; Protein Binding; Rabbits; Salicylates; Testosterone