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Biomedical subjects

A Marzo

Publications and source records attributed to A Marzo.

At least 109 records · Page 6Linked to original sources
PubMed1979

Bioavailability and related heart function index of digoxin capsules and tablets in cardiac patients.

A loading dose of digoxin (750 microgram) in two commercial formulations was administered to 14 patients with heart disease according to a crossover design. One formulation consisted of soft gelatin capsules containing a solution of digoxin; the other formulation was compressed tablets. All parameters investigated, i.e., serum peak height, time of the peak, area under the serum level--time curve (AUC), and area above the Q--S2I (electromechanical systole) decrease (obtained from polycardiographic evaluation), showed better bioavailability of digoxin capsules than tablets, averaging 36.3%. The better bioavailability of digoxin capsules than tablets seems to be more evident in heart disease patients than that encountered previously in healthy subjects. The AUC and the area above the Q-S2I decrease were linearly correlated only with digoxin capsules.

Adult↗
PubMed1979

Pharmacological and toxicological properties of creatinol O-phosphate. A review.

N-Methyl-N-(beta-hydroxyethyl)guanidine O-phosphate (creatinol O-phosphate, COP) has proved to possess anti-ischemic and anti-arrhythmic activities associated with improved ionic balance and heart performance. These activities, which have also been shown in clinical studies, are more evident in pharmacological and clinical conditions involving a hypoxic damage of the heart muscle. Pharmacokinetic studies have shown that absorption of COP administered i.m. is complete. COP is distributed in all organs, and in particular, in the kidney, liver and myocardium. After being dephosphorylated, this drug is eliminated with urine. Dephosphorylation of COP occurs in the kidney and liver. COP crosses the membrane of the myocardial cell, concentrating in the cytosoluble fraction. The results of the toxicological studies confirm that COP has no side effects, is excellently tolerated and has a favourable therapeutic index.

Animals↗
PubMed1979

Protective action of creatinol O-phosphate against serum CPK activity enhanced by isoprenaline in the rat.

Isoprenaline (ISP) in the rat (500 mg/kg s.c.) was shown to be able to enhance the creatin phosphokinase activity (CPK) in serum from 135 U/l in the control animals to about 600 U/l in 5 h, i.e. at the peak. When the rats were pretreated with N-methyl-N-(beta-hydroxyethyl)guanidine O-phosphate (creatinol O-phosphate, COP), the CPK enhancement was reduced to an extent related to the doses of COP (250, 500 and 1000 mg/kg i.p.). COP protection was about 16% with the lower dose but increased to 50% with the highest dose according to linear regression (COP doses versus CPK levels, p less than 0.01). The protective action against serum CPK enhancement evoked by ISP is common to other classes of drugs, such as beta-blocking agents, calcium antagonists and corticosteroids. In the case of COP and calcium antagonists a common mechanism, which has the effect or reducing myocardial calcium overload due to ISP, may be assumed on the basis of other previous investigations on the ion balance across the heart cell membrane and on the uptake and subcellular distribution of COP in the isolated perfused rat heart.

Animals↗
PubMed1978

Preliminiary data on the pharmacokinetics of glaziovine in man.

The pharmacokinetic parameters of Glaziovine, a pro-aporphine alkaloid with neuropharmacological properties, were investigated in healthy human volunteers. Glaziovine-14C 20 mg was administered in capsules (oral route) and in vials (i.v. route). Total radioactivity was meausred in plasma, urine and faeces. When administered orally, peak plasma levels were encountered at 2 h. The cumulative urinary excretion of total radioactivity over a 24 h period was 38% after oral and 50% after i.v. administration. Investigation of metabolites in urine revealed Glaziovine glucuronide as the sole metabolite of the drug. By comparing the percentage of urinary excretion or the area under the plasma level-time curve (AUC) obtained in the first 24 hours after i.v. and oral administration, enteral absorption was found to range from 78 to 84%. Thus, glaziovine appears to show very high enteratral absorption.

Aporphines↗
PubMed1978

Tissues concentration and excretion of deslanatoside C-3H in newborn and growing rabbits.

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.

Aging↗
PubMed1978

Pharmacokinetics of deslanatoside C-3H administered parenterally to the guinea-pig, rabbit and dog.

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.

Animals↗
PubMed1977

Bioavailability of digoxin in a new soluble pharmaceutical formulation in capsules.

The in vitro dissolution and the bioavailability of two pharmaceutical formulations of digoxin were compared, one being a common commercial tablet form and the other a solution of the glycoside in soft gelatin capsules. Digoxin capsules dissolved more readily in vitro and showed higher bioavailability than digoxin tablets in both dogs and humans. In dogs, the capsules and tablets were compared with an elixir of digoxin, which possesses complete bioavailability. The better bioavailability of digoxin capsules as compared with tablets may be explained by the fact that this formulation contains the cardiac glycoside in a solution.

Adult↗
PubMed1977

Bilary and urinary excretion of five cardiac glycosides and its correlation with their physical and chemical properties.

Biliary and urinary excretion of five tritium-labelled cardiac glycosides, i.e. Ouabain, K-strophanthoside, Digoxin, Digitoxin and Deslanatoside C, were investigated in anaesthetized guinea-pigs 5 h after i.v. or enteral administration. Urinary excretion is the main route of elimination in the case of Ouabain and Deslanatoside C. Conversely, biliary excretion is predominant in the case of Digoxin and Digitoxin. K-strophanthoside is excreted both via bile and urine. In conscious guinea-pigs treated i.v. with the same cardiac glycosides the highest levels were observed in urine, bile, kidneys and liver. The relative values of those levels were in agreement with the excretion pattern observed in anaesthetized animals. An inverse linear relation (P less than 0.05) was encountered between biliary excretion rate and polarity of glycoside molecula. This correlation has been previously observed by other authors in other species, but not in the rabbit. This suggests that the correlation may not be considered generally applicable at present.

Animals↗
PubMed1977

Absorption and excretion of 3H-raubasine in human subjects and dogs.

The pharmacokinetic behavior of (3,5,6-3H)-raubasine (RAU) was investigated in human subjects after oral administration and in dogs after both intravenous and oral administration. By the oral route RAU peak plasma levels appeared in human subjects after 1 h and in dogs after 2 h. Three-day cumulative urinary excretion was 22% by i.v. route and 13% by oral route in dogs, being 29% in human subjects after oral administration. Three-day cumulative faecal excretion in dogs was 51% by i.v. route and 57% by oral route whilst it was 24% in humans. From a comparison between the urinary excretion values observed after i.v. and oral administration, a RAU intestinal absorption of 59% may be obtained.

Administration, Oral↗
PubMed1977

Absorption, fate and excretion of glaziovine-14C in the dog.

The pharmacokinetic parameters of glaziovine, a proaporphine alkaloid with neuropharmacological properties, were investigated in dogs. At alkaline pH, glaziovine-14C showed a very high partition coefficient value from a buffered water solution and both benzene and chloroform. When administered i.v. to both conscious and anaesthetized dogs, levels of glaziovine-14C were higher in the heart, liver, kidneys and brain, and lower in skeletal muscle, skin and plasma. The high amount of radioactivity found in the small intestine as well as that found in bile obtained from a biliary fistula demonstrates that glaziovine is excreted both via the bile and via urine in not dissimilar amounts at least in dogs. When administered orally, peak plasma levels were encountered in 1 hr. Cumulative urinary excretion of glaziovine over a 24 hr period was 49% after the i.v. route and 39% after the oral route. By comparing the percentage of urinary excretion or the area under the plasma level time curve (AUC) obtained in the first 24 hr after i.v. and oral administration, percentages of bioavailability were obtained ranging from 80 to 98%. Glaziovine thus seems to possess a very high enteral absorption.

Absorption↗
PubMed1976

Plasma turnover and excretion of K-strophanthoside-3H in human volunteers after parenteral administration.

Pharmacokinetic parameters of K-strophanthoside-3H, a short-acting cardiac glycoside, were investigated in healthy subjects, patients suffering from heart disease, renal failure and in cholecystectomized patients with a biliary T-tube inserted surgically, after parenteral administration of 250 mug of the glycoside. The healthy subjects, patients suffering from heart disease and those with the biliary T-tube showed a dominant half-time for plasma turnover of the glycoside of 15-16 h after the i.v. route and 18-22 h after the i.m. route and cumulative urinary excretion of the drug over a 24 h period of 37-42% (i.v. route) and 32-33% (i.m. route). The volumes of distribution were lower in patients with heart disease and patients with biliary fistula than in the healthy subjects. In patients suffering from renal failure the dominant half-time of plasma turnover was higher (33 h), while cumulative urinary excretion of the glycoside (12%) and the volumes of distribution were lower than in the healthy subjects. A peak of plasma levels 30 min after i.m. administration of K-strophanthoside-3H leads to the conclusion that this glycoside is rapidly absorbed when injected intramuscularly.

Bile↗