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Biomedical subjects

J J Ross

Publications and source records attributed to J J Ross.

At least 73 records · Page 4Linked to original sources
PubMed1981

Absorption and bioavailability of captopril in mice and rats after administration by gavage and in the diet.

The absorption of captopril (I), a new antihypertensive agent, was studied in mice and rats at doses (50 and 1350 mg/kg) administered in the diet in chronic toxicological studies. 3H- or 35S-Labeled I was administered by gavage and in the diet to male and female animals in a two-way crossover study. Animals received daily doses of nonradiolabeled I in the diet for 25 days, except on Days 15 and 22 when radiolabeled I was administered either by gavage or in the diet. Absorption of the total radioactivity in 2-month-old mice averaged 49 and 48%, respectively, of the 50- and 1350-mg/kg doses given in the diet and 57 and 65%, respectively, of the doses given by gavage. The bioavailability of I in 2-month-old mice averaged 48 and 39% (diet) and 44 and 59% (gavage) of the 50- and 1350-mg/kg doses, respectively. In 2-month-old rats, absorption of the total radioactivity averaged 41% of the 50-mg/kg dose given in the diet. In 2- and 15-month-old rats, minimum absorption of the 1350-mg/kg dose averaged 36 and 45% (diet) and 51 and 71% (gavage), respectively; the minimum bioavailability averaged 20 and 29% (diet) and 39 and 44% (gavage), respectively. These studies demonstrate adequate absorption and bioavailability of I over a wide range of doses from the drug-diet mixtures and by young and old animals and also illustrate a useful experimental design for the estimation of relative oral absorption of a drug administered continuously in the diet over several days.

Animals↗
PubMed1981

Pharmacokinetics of captopril in dogs and monkeys.

[14C]Captopril was given as a priming dose, followed by constant intravenous infusion for 4 or 6 hr, to three anesthetized dogs and three anesthetized monkeys. Blood, urine, and bile samples were collected during and after drug infusion. Pharmacokinetic evaluations were carried out exclusively on data obtained for unchanged captopril. The average total body clearance (ClT) and the renal clearance (ClR) of captopril, in milliliters per kilogram per hour, were 605 and 341 in the dog and 1135 and 944 in the monkey. The biliary clearance of captopril was negligible in both species. The greater difference between the ClR and ClT values in the dog compared to that in the monkey was the result of more extensive metabolism of captopril by the dog. Since almost all of the radioactive dose was recovered in urine in both species, captopril and its metabolites were almost exclusively eliminated by the kidneys. One primary reason that body and renal clearance values of captopril were much greater in the monkey than in the dog was that the net tubular secretion fo captopril was about three times greater in the monkey (82%) than in the dog (28%). The volume of distribution of captopril was higher in the monkey (3.6 liters/kg) than in the dog (2.6 liters/kg); the volume of the central compartment was about the same (0.5 liter/kg) for both species. The terminal half-life value was slightly higher in the dog (2.8 hr) than in the monkey (2.2 hr).

Anesthesia↗
PubMed1979

Metabolism of tritium- and carbon-14-labeled tiamulin in dogs, rats, and pigs.

The metabolism of tiamulin hydrogen fumarate, labeled with 3H, 14C, or both, was studied in dogs, rats, and weanling pigs. After a dose of radiolabeled tiamulin, all three species excreted more radioactivity in feces (via bile) than in urine. Dogs absorbed 86% of a single oral dose of tiamulin-3H, and the disposition of the compound was similar after a single or multiple dosage regimen. The ratio of antimicrobial activity to total radioactivity in dog plasma was only about 0.25, and was still less in dog urine. After dosing with tiamulin-14C, rats and pigs excreted at least 1% of the dose as 14CO2 in expired air. In dual-labeled studies, pigs excreted less total 14C than 3H and had greater residues of 14C than 3H in edible tissues, blood, and plasma. After the administration of tiamulin-14C to pigs, radioactivity was incorporated into liver glycogen, indicating metabolic cleavage of the side chain of tiamulin. Tiamulin-3H is the isotopically-labeled compound of choice for studying metabolism and tissue residues in animals.

Administration, Oral↗
PubMed1978

Absorption of the beta-adrenergic-blocking agent, nadolol, by mice, rats, hamsters, rabbits, dogs, monkeys, and man: an unusual species difference.

1. Dogs absorbed [14C]nadolol almost completely (88--104%) after oral administration of 10--75 mg/kg. In contrast, mice, rats, hamsters, and rabbits, given oral doses of 20 mg/kg, absorbed, at most, 25%. After administration of oral doses of 2--75 mg/kg, monkeys absorbed no more than an average of 30%. Six monkeys given oral doses of 10 mg/kg absorbed 12--44%. 2. In rats, [14C]nadolol was orally absorbed to an average of 13.7--17.5%, whether given in suspension or in solution, indicating that absorption was not limited by rate of dissolution nor by solubility. 3. Mildly hypertensive humans given single doses of [14C]nadolol (2 or 80 mg, orally) and normal subjects given single doses (10 mg, orally) absorbed an average of 20.4--33.3%.

Adrenergic beta-Antagonists↗
PubMed1976

Release and elimination of 14C-fluphenazine enanthate and decanoate esters administered in sesame oil to dogs.

The rates of release of 14C-fluphenazine enanthate and 14C-fluphenazine decanoate were compared in two groups of five male dogs. Each dog was given a single dose (2 mg/kg im) of either the enanthate or decanoate ester in sesame oil. The times required to attain maximum concentrations of radioactivity in plasma were 3.8 +/- 0.5 days (+/-SE) for the enanthate ester and 10.6 +/- 1.1 days for the decanoate ester (p less than 0.001); maximum concentrations of radioactivity in the plasma at these times were 16.7 +/- 1.1 and 11.1 +/- 1.2 ng/ml, respectively (p less than 0.01). However, 35 days after dosing, the concentrations of radioactivity in plasma were greater for the decanoate ester than for the enanthate ester. The times required for 50% of the dose to be excreted in the urine and feces were 7.8 +/- 0.5 days for the enanthate ester and 22.6 +/- 4.4 days for the decanoate ester (p less than 0.05). The total amounts excreted in 35 days were 85.4 +/- 1.8 and 68.8 +/- 6.6% of the dose for the enanthate and decanoate esters, respectively; the average half-times for the rates of release of radioactivity from depot and body, as calculated from the data for total excretion, were 5.55 days for the enanthate ester and 15.4 days for the decanoate ester. Thirty-five days after dosing, the amount of the dose present in the injection site was 4.6 +/- 1.6% for the enanthate ester and 18.6 +/- 5.7% for the decanoate ester. Two groups of six dogs each were protected against the emetic effects of apomorphine more than twice as long by the decanoate ester than by the enanthate ester after the subcutaneous administration of single 8-mg/kg doses of either drug in sesame oil (p less than 0.05). Based on measurements of total radioactivity, it was concluded that the decanoate ester was released from the depot at less than one-half the rate of the enanthate ester.

Animals↗
PubMed1976

Fluphenazine enanthate and fluphenazine decanoate: intramuscular injection and esterification as requirements for slow - release characteristics in dogs.

14C-Fluphenazine base was administered intramuscularly in sesame oil to five male beagles (2 mg/kg). The concentration of radioactivity in plasma and the excretion of radioactivity in urine and feces were measured for 14 days. Maximum concentrations of radioactivity were found in plasma 2 hr after administration. These levels declined with elimination half-lives of 3.20 hr during the 2-12-hr interval after dosing and of 4.02 days during the 2-14-day interval. Most administered radioactivity was excreted during the first 2 days after dosing, predominantly in the feces. An average of 0.43% of the dose was present at the injection site 14 days after dosing; some residual radioactivity was found in the liver and in the ocular portion consisting of the combined retina, choroid, and sclera. 14C-Fluphenazine and its enanthate and decanoate esters were each administered intravenously to three different groups of intact dogs at doses of 1 mg/kg. Regardless of which compound was administered, concentrations of radioactivity in the plasma of these dogs were comparable. Thirty minutes after these dogs had been dosed with 14C-fluphenazine enanthate or 14C-fluphenazine decanoate, most radioactivity in the plasma was present as 14C-fluphenazine base and other unidentified metabolites; at this time, at least 79% of either of the two 14C-fluphenazine esters had been biotransformed. The excretion of radioactivity by these same three groups of dogs was very similar, regardless of which of the compounds was given. In 7 days, an average of only 3-4% of the dose was excreted in urine; the remainder was excreted in feces. 14C Fluphenazine and its enanthate and decanoate esters (1 mg/kg) were administered intravenously to dogs whose bile ducts had been cannulated. The amounts of radioactivity excreted in the urine and bile in 8 hr were very similar, as were the residual amounts of radioactivity present in selected tissues. Comparison of the data obtained from dogs given these three compounds intravenously (unformulated) or intramuscularly in sesame oil points to the following conclusions: (a) fluphenazine base per se does not provide slow-release characteristics unless it has been esterified, for example, with heptanoic or decanoic acid, and (b) intramuscular rather than intravenous administration of these two esters is responsible for producing their slow-release characteristics.

Animals↗