Search PubMed⌕ Search

Biomedical subjects

A Black

Publications and source records attributed to A Black.

161 records · Page 9Linked to original sources
PubMedDate not supplied

Metabolic disposition of Rolziracetam in laboratory animals.

The metabolic disposition of [14C]-labeled Rolziracetam (CI-911) was studied in rhesus monkeys, beagle dogs, and Wistar rats after both p.o. and i.v. doses. Intravenously administered CI-911 was rapidly eliminated from systemic circulation with an apparent elimination half-life of less than 25 min. Plasma radioactivity was 10-20 times higher than that of parent drug and persisted much longer. After oral doses, only traces of intact drug were detected in plasma, whereas total radioactivity reached peak concentrations within 0.5-1 h indicating rapid absorption. The extent of absorption determined from plasma radioactivity and urinary excretion data was 90% or better. Tissue distribution of radioactivity in rats showed the highest concentrations in the liver and kidneys (12-30 times greater than plasma levels) with decreasing levels in the lungs, gonads, heart, spleen, muscle, and brain. Urinary excretion accounted for nearly 90% of the administered dose while fecal recovery was less than 5%. The sole metabolite present in plasma, tissues, and urine was identified as 5-oxo-2-pyrrolidinepropanoic acid (PD 106,687).

Administration, Oral↗
PubMedDate not supplied

Metabolic disposition of the non-steroidal anti-inflammatory agent isoxicam in man.

The metabolic fate of isoxicam, a long half-life non-steroidal anti-inflammatory agent, in human subjects was investigated using isoxicam labelled with 14C in the N-methyl position. Three healthy male subjects were each administered a single oral 200 mg dose (90.7 microCi) with plasma and urine collected. Total plasma radioactivity peaked between 8 and 24 h postdose with mean 14C plasma radioactivity half-life of 36.1 h. Low levels of plasma radioactivity precluded plasma metabolic profiling. In urine, 37% of the administered radioactivity was recovered through 168 h. Metabolic profiling of urine confirmed the major oxidative excretion product as the hydroxymethylisoxazole metabolite. Identified and confirmed as minor urinary metabolites were radiolabelled open-ring sulfonamide and N-methylsaccharin. Non-labelled saccharin formed by oxidative loss of the 14C N-methyl group from N-methylsaccharin, was also observed. The role of this 'saccharin pathway' in the overall human disposition of isoxicam remains to be elucidated.

Adult↗
PubMedDate not supplied

Major depression in primary care practice. Clinical characteristics and treatment implications.

Major depression is thought to be underdiagnosed and undertreated in primary medical care facilities. The authors conducted a clinical trial that included a three-phase assessment so only ambulatory medical patients judged eligible for treatment of this disorder in medical settings were recruited. In addition to administering the Center for Epidemiologic Studies-Depression scale and the Diagnostic Interview Schedule's (DIS) Depression section, the psychiatrists evaluated the DIS-positive patients. This third assessment determined that clinical characteristics of DIS-positive patients were such that 70% of the patients could be treated for major depression in a primary care setting, 13% should probably be referred to a mental health facility, and 17% were experiencing conditions other than major depression.

Adolescent↗
PubMedDate not supplied

Cocaine use associated with increased suicidal behavior in depressed alcoholics.

The aim of this study was to determine whether depressed alcoholics who used cocaine would display a higher prevalence of suicidal behavior and suicidal ideation than depressed alcoholics who did not use cocaine. Forty-one depressed alcoholics participated in this prospective study of consecutively admitted inpatients. Seventeen patients (41.5%) had made a suicide attempt during their current depressive episode, and all but 1 of these attempts occurred during the week prior to their hospitalization. Ten patients used cocaine in the week prior to hospitalization, and 7 of these 10 (70%) had made a suicide attempt during that week. In contrast, only 32% of the depressed alcoholics who did not use cocaine made a suicide attempt during that week (p < .05). Suicidal ideation was also more prevalent in alcoholics who used cocaine. These data provide evidence that cocaine use is associated with an increased prevalence of suicidal behavior and suicidal ideation in depressed alcoholics.

Adult↗
PubMedDate not supplied

Nonhuman primate models of skeletal and reproductive aging.

BACKGROUND: Bone loss, osteoarthritis (OA) and age-related changes in reproduction are some of the most apparent and troubling results of advancing age in the human population. The significance of these changes underscores the need for developing appropriate animal models to study aging of bone and the reproductive system. OBJECTIVE: This review surveys the literature regarding the current state of nonhuman primates (NHP) as models for skeletal and reproductive aging in humans. RESULTS: Several species of NHP exhibit age-related bone loss as well as changes in the mineral content and architecture of bone that are similar to those reported in humans. In addition, since aged females of some species of NHP exhibit cessation of menses and serum hormone profiles consistent with those described in peri- and premenopausal women, they provide useful models of postmenopausal bone loss. Sensitivity to surgical estrogen depletion and hormone replacement has also been demonstrated in female NHP. Spontaneous development of degenerative arthritis, analogous to humans in age at onset, joint involvement and histologic changes, suggest that NHP are suitable for the study of human OA. Many similarities exist between female NHPs and women in age-related changes in reproductive function including hormone concentrations, menstrual cycling, fertility and the development of endometriosis. Changes in male sexual behavior and fertility with age are also comparable in men and male NHP. CONCLUSIONS: Genetic similarity, long lives and similar reproductive endocrinology suggest that NHPs are likely candidates as models of skeletal and reproductive aging in humans. Current data confirm that several species of NHP exhibit changes in bone and reproduction that are comparable to those known to occur in humans.

Aging↗
PubMedDate not supplied

In vivo metabolism of isoxicam in rats, dogs, and monkeys.

Isoxicam is a long half-life nonsteroidal anti-inflammatory agent which undergoes extensive metabolism prior to elimination in animals and man. The major route of isoxicam transformation is hydroxylation of the methylisoxazole functionality to form hydroxymethylisoxicam, and cleavage of its benzothiazine moiety to give an oxoacetic acid metabolite. The metabolic pathway for scission of the benzothiazine moiety to the oxoacetic acid metabolite and to other potential metabolites is not known. To gain additional information on the metabolic fate of isoxicam, 14C-isoxicam labeled on the N-methyl group was administered to rats, dogs, and monkeys with urine and feces collected for metabolic profiling and identification. Identified as new metabolites of isoxicam were an open-ring sulfonamide, N-methylsaccharin, and saccharin. The formation of these metabolites suggests that isoxicam undergoes direct oxidative scission of its benzothiazine ring at carbon atom 3 to generate the observed open-ring sulfonamide, N-methylsaccharin, and oxoacetic acid metabolites.

Animals↗
PubMedDate not supplied

Small is beautiful?

Explore the source record for details and available documents.

England↗
PubMedDate not supplied

Biodisposition studies with the acyl-coenzyme A: cholesterol acyltransferase inhibitor 2,2-dimethyl-N-(2,4,6-trimethoxyphenyl)dodecanamide, CI-976.

2,2-Dimethyl-N-(2,4,6-trimethoxyphenyl)dodecanamide, CI-976, is a newly developed fatty acid anilide being evaluated as a plasma lipid regulator and antiatherosclerotic agent. Disposition studies with CI-976 were conducted in rats and monkeys. In rats, CI-976 (suspension, 50 mg/kg) was approximately 30% bioavailable, with 46% of the administered radioactivity recovered in urine suggesting presystemic metabolism. The intravenous elimination half-life of CI-976 in rats was approximately 8 hr. Radioactivity derived from [14C]CI-976 was almost completely recovered in rats after either oral or intravenous administration. In bile duct-cannulated rats receiving either an oral or intravenous dose, biliary excretion was the major route of drug-derived radioactivity elimination. There was no evidence for unchanged drug in urine or bile. In monkeys, 13% urinary recovery and 5% bioavailability was achieved after a single 50 mg/kg suspension dose. Similar values were obtained following a 250 mg/kg dose. Monkeys displayed a CI-976 elimination half-life of 0.6 hr after a 2 mg/kg intravenous dose. No unchanged drug was excreted in urine. In summary, CI-976 exhibits moderate absorption and bioavailability in the rat, but lower absorption and bioavailability in monkey. A special difference in CI-976 elimination half-life was observed consistent with in vitro metabolism results.

Administration, Oral↗