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Biomedical subjects

R A Ronfeld

Publications and source records attributed to R A Ronfeld.

23 records · Page 2Linked to original sources
PubMed1975

Dose dependent kinetics of carbamazepine in the monkey.

The blood concentration-time curve of carbamazepine in monkeys following intravenous infusion of the drug at two different levels was determined using a specific gas liquid chromatographic assaymconcentration values measured over a two and one-half decade concentration range during zero order infusion as well as the decay portion of the curve for both doses were computer fit using a nonlinear least-squares program and found to follow Michaelis-Menten kinetics. There was little change found in the volume of distribution for carbamazepine from monkey to monkey, however, marked differences were noted in the metabolic rate constants.

Animals↗
PubMedDate not supplied

Characterization of a carbamic acid ester glucuronide of the secondary amine sertraline.

In the dog, the major excretory metabolite of the antidepressant sertraline was characterized as sertraline carbamoyl-O-glucuronide. The intact conjugate was isolated from bile by HPLC. The metabolite was labile to beta-glucuronidase and produced sertraline as the single hydrolytic product, based on HPLC and GC-MS analyses. By fast atom bombardment MS analysis, [M+H]+ and [M+Na]+ ions at m/z 526 and 548 were observed, as were the proton and sodium adducts of the aglycone (m/z 350 and 372) due to cleavage of the glycosidic bond and elimination of the glucuronic acid moiety (176 amu). The observed mass of the aglycone was 44 amu greater than sertraline, indicating that a carbamic acid of this secondary amine was conjugated with glucuronic acid. These data suggest that sertraline in solution reversibly associates with CO2 before formation of sertraline carbamoyl-O-glucuronide. This novel amine glucuronide was also identified in human plasma after the oral administration of sertraline to each of seven subjects. The glucuronide was stable in plasma at both acidic and basic pH.

1-Naphthylamine↗
PubMedDate not supplied

Metabolism and disposition of the 5-hydroxytryptamine uptake blocker sertraline in the rat and dog.

Sertaline [1S,4S-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1- naphthalenamine] is a potent and selective inhibitor of neuronal serotonin uptake and is currently under development for the treatment of depression and of obesity. The drug is greater than 97% bound to plasma proteins, yet extensively distributes into tissues. The whole brain concentration of sertraline in the rat is more than 40-fold higher than that in plasma, and the volume of distribution is about 25 liters/kg in the rat and dog. Sertraline is extensively metabolized by the rat and dog prior to excretion. The metabolic clearance of sertraline is greater than 35 ml of blood/min/kg in each species, and first-pass metabolism occurs with oral administration. Initial metabolic steps include N-demethylation, N-hydroxylation, oxidative deamination, and glucuronidation of sertraline carbamic acid, which in solution is in equilibrium with sertraline and carbon dioxide. The N-desmethyl metabolite, which is 10-fold less potent as an inhibitor of serotonin uptake, is formed in both species. Plasma AUC for desmethyl-sertraline is 66 to 270% of that for sertraline, and is dependent on the species examined and route of drug administration. Sertraline and desmethyl-sertraline undergo oxidative deamination to the corresponding ketone, which is subsequently hydroxylated at the alpha-carbon, forming a diastereomeric metabolite pair. The glucuronides of sertraline carbamic acid, N-hydroxy sertraline, and the alpha-hydroxy ketone diastereomers comprise 45% and 82% of the total radiolabel excreted in urine and bile of bile duct-cannulated rats and dogs, respectively. Bile is the major route of elimination in both species.

1-Naphthylamine↗