ABSTRACT
Feeding deacetyllanatoside C to senescent shoot cultures of Digitalis lanata resulted in the formation of a new product, which was isolated by semi-preparative HPLC. The molecular structure was elucidated by means of HPLC-mass spectrometry and NMR as 21'-di-dehydro-deacetyllanatoside C.
Subject(s)
Deslanoside/analogs & derivatives , Deslanoside/metabolism , Digitalis/metabolism , Plants, Medicinal , Plants, Toxic , Biotransformation , Carbohydrate Conformation , Carbohydrate Sequence , Cells, Cultured , Cellular Senescence , Chromatography, High Pressure Liquid , Digitalis/cytology , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Sequence Data , Oligosaccharides/chemistry , Oligosaccharides/isolation & purificationABSTRACT
Digitalis glycosides continue to place high on the list of prescribed drugs. Digoxin is 8th on prescriptions written in the United States in 1980, digitoxin 16th, and digitalis leaf 23rd. There is little doubt that most physicians continue to believe these drugs are useful. The application of more definite indications, smaller doses, and the recognition of the role of pharmacokinetics and drug interactions make use of the glycosides more challenging than ever before in 1985.
Subject(s)
Arrhythmias, Cardiac/drug therapy , Digitalis Glycosides/therapeutic use , Heart Failure/drug therapy , Administration, Oral , Adrenergic beta-Antagonists/therapeutic use , Age Factors , Anti-Arrhythmia Agents , Antihypertensive Agents/adverse effects , Biological Availability , Bretylium Tosylate/therapeutic use , Deslanoside/metabolism , Digitalis Glycosides/adverse effects , Digitoxin/metabolism , Digoxin/blood , Digoxin/therapeutic use , Dose-Response Relationship, Drug , Drug Interactions , Humans , Injections, Intramuscular , Injections, Intravenous , Intestinal Absorption , Kidney Failure, Chronic/metabolism , Lidocaine/therapeutic use , Metabolic Clearance Rate , Myocardial Infarction/metabolism , Obesity/metabolism , Phenytoin/therapeutic use , Potassium/metabolism , Pulmonary Heart Disease/metabolism , Thyroid Diseases/metabolismSubject(s)
Digitalis Glycosides/toxicity , Animals , Biological Availability , Deslanoside/metabolism , Digitalis Glycosides/administration & dosage , Digitalis Glycosides/blood , Digitalis Glycosides/metabolism , Digitoxin/administration & dosage , Digitoxin/metabolism , Digitoxin/toxicity , Digoxin/administration & dosage , Digoxin/metabolism , Digoxin/toxicity , Drug Interactions , Electrolytes/metabolism , Erythrocytes/metabolism , Humans , Intestinal Absorption/drug effects , Kinetics , Lanatosides/metabolism , Myocardial Infarction/drug therapy , Ouabain/metabolism , Protein Binding/drug effects , Saliva/metabolism , Strophanthidin/analogs & derivatives , Strophanthidin/metabolismSubject(s)
Deslanoside/metabolism , Lanatosides/metabolism , Adolescent , Adult , Aged , Deslanoside/administration & dosage , Female , Humans , Injections, Intravenous , Kinetics , Male , Middle AgedSubject(s)
Deslanoside/metabolism , Lanatosides/metabolism , Administration, Oral , Adolescent , Adult , Aged , Female , Humans , Kinetics , Male , Middle AgedSubject(s)
Bile/metabolism , Deslanoside/metabolism , Lanatosides/metabolism , Deslanoside/blood , Deslanoside/urine , HumansABSTRACT
The pharmacokinetics of Deslanatoside C-3H, a short-acting polar cardiac glycoside, were investigated in the guinea-pig, rabbit and dog, after parenteral administration. Deslanatoside C was on average 20% plasma protein-bound and had a red blood celle/plasma partition ratio of 1/9. Tissue uptake of Deslanatoside C observed in the guinea-pig seems on average to be higher than in rabbits. Among the various organs and fluids tested, the highest levels were encountered in the urine, bile and kidneys of both the guinea-pig and rabbit. The main excretory route of this glycoside was via the urine, although significant amounts were excreted via the bile in all the three species tested. Cumulative urinary excretion 24 hr after i.v. injection was 50% (75% of which in unchanged form) in the guinea-pig, 46.5% (86% of which in unchanged form) in the rabbit, and 42.9%(84% of which in unchanged form) in the dog. Among the cardiac glycosides, Deslantoside C seems to possess the highest urinary excretion rate, which has in fact also recently been confirmed in human subjects.
Subject(s)
Deslanoside/metabolism , Lanatosides/metabolism , Animals , Blood Proteins/metabolism , Deslanoside/administration & dosage , Dogs , Drug Stability , Erythrocytes/metabolism , Guinea Pigs , In Vitro Techniques , Injections, Intramuscular , Injections, Intravenous , Kinetics , Protein Binding , Rabbits , Species SpecificityABSTRACT
Deslanatoside C-3H was injected (i.p. 50 microgram/kg) into rabbits of 1, 4, 10, 20 days and more than 1 year old. The rabbits were sacrificed 2 and 6 h after dosing. Levels in all tissues were higher in newborn rabbits, decreased in the older animals and then in most tissues increased in adults to different degrees, showing the highest values in kidneys. Biliary excretion and above all urinary excretion increased with age. Levels in atria, ventricles, aorta and liver in rabbits 1 and 4 days old were consistently higher at the 6th h than those at the 2nd h, these tissues showing a particularly marked avidity with Deslanatoside C; in the older animals this behaviour was reversed. These data and those of other Authors working on other glycosides (incleding Digoxin) and other species (including newborn children) lead to the conclusion that digitalis glycosides in new born species are excreted at a lower rate and incorporated in the body tissues at a higher rate than in adults. They may also in part explain the large dosages employed in human infants in comparison with adults, as the higher distribtuion volume retains a large amount of the injected glycoside.
