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Biomedical subjects

T B Cooper

Publications and source records attributed to T B Cooper.

277 records · Page 16Linked to original sources
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The disposition of benzoylecgonine in maternal and fetal rats.

We tested our hypothesis that pregnancy alters the pharmacokinetic profile of benzoylecgonine, and that this metabolite accumulates in the fetus longer than in the mother. Chronically catheterized near-term pregnant and nonpregnant female Sprague-Dawley rats received an intravenous infusion of benzoylecgonine over a period of 30 min. Adult or fetal blood and tissue samples were obtained either at the end of the infusion or 6 h postinfusion for analysis of benzoylecgonine and other cocaine metabolite concentrations via gas chromatography/mass spectrometry (GC/MS). Pregnancy altered benzoylecgonine pharmacokinetics. At the end of the infusion, benzoylecgonine concentration in the fetal plasma was markedly lower than in the maternal plasma with a fetal/maternal ratio of 0.14+/-0.01. A significantly lower concentration of benzoylecgonine was found in both maternal and fetal brain at 0 h postinfusion, with tissue/plasma concentration ratios of 0.04 and 0.24, respectively, suggesting that benzoylecgonine does not readily penetrate into the brain. At 6 h, the fetal concentration of benzoylecgonine was significantly higher than in the corresponding maternal blood and tissues. Ecgonine methyl ester, a metabolite of benzoylecgonine was found in the maternal liver, but not in the fetus. In addition, the amniotic fluid concentration of benzoylecgonine became significantly higher in the 6-h postinfusion samples as compared to the end of infusion value, suggesting that repeated intrauterine exposure to cocaine may cause an accumulation of benzoylecgonine in the fetus.

Animals↗
PubMedDate not supplied

Long-term intravenous perinatal cocaine exposure on the mortality of rat offspring.

To examine the effects of chronic perinatal cocaine exposure, cocaine was administered intravenously throughout pregnancy and the postpartum period to the rat. Pregnant rats were divided into five groups: nontreated (naive); normal saline control (saline); cocaine first generation (cocaine); saline in the first generation and cocaine in the second generation (Sal-2G); and cocaine in both first and second generations (Coc-2G). The rats receiving cocaine in the second generation (Sal-2G and Coc-2G) were offspring of the saline and cocaine group, respectively. All cocaine-treated groups received cocaine 2 mg/kg/day intravenously (IV), and the saline group received normal saline 0.2 ml/day IV from GD 2 to the 21st day postpartum. Mean perinatal mortality was greater in all pups exposed to cocaine in utero during gestation; Cocaine (6.4%); Sal-2G (5.6%); Coc-2G (11.4%) groups than in the noncocaine groups (3.2%, 1.3%). Weight gain, physical, and neurological developments of the offspring were not affected. It was concluded that perinatal cocaine exposure had an increased perinatal mortality even at doses approximately 10 times lower than those previously reported, which were administered by extravascular routes. These findings indicate the importance of the route of drug administration in perinatal cocaine research.

Analysis of Variance↗
PubMedDate not supplied

GLC/MS assay for loxapine in human biofluids and tissues with deuterium labeled analog as an internal standard.

A quantitative gas liquid chromatographic-mass spectrometric (GLC/MS) assay was developed for the determination of loxapine in human blofluids and tissues. The assay utilizes selected ion monitoring in a GLC effluent of the molecular ion of loxapine generated by electron-impact ionization (EI). Loxapine-d3 was used as the internal standard. The assay can measure 2 ng/mL of loxapine with about 6% precision. The curve relating the amounts of loxapine added in control plasma versus the ion intensity ratio (m/e 327/330) over a large range of loxapine concentrations was linear with essentially zero intercept. The method was used for the analysis of loxapine in human urine, plasma, brain, liver, lung and spleen.

Brain Chemistry↗
PubMedDate not supplied

Plasma level monitoring of antipsychotic drugs.

Psychotic patients treated with identical doses of antipsychotic drugs have been shown to have great interindividual differences in their steady state plasma concentration. Therefore, monitoring treatment by dosage adjustment alone is of little value. If antipsychotic blood levels can be related to clinical response then their routine measurement may well result in well defined guidelines to individualised optimal dosage. Despite the considerable effort expended in this field and the many interesting testable hypotheses generated, little substantive evidence for an acceptable plasma level monitoring guide has been reported to date. Work on metabolite level profiles, intra- and extracellular drug concentration differences, more detailed clinical rating scales, and improved experimental design, all show great promise for the future. Investigation of the pharmacokinetics and the elucidation of the often complex metabolic pathways of individual antipsychotic drugs are generating the data base required for the rational pharmacotherapy of these most severely ill patients. Until more data are available, routine monitoring of antipsychotic drug plasma levels remains of research interest.

Antacids↗
PubMedDate not supplied

Pharmacokinetics of bupropion and metabolites in plasma and brain of rats, mice, and guinea pigs.

Recent reports indicate that bupropion, a novel non-tricyclic antidepressant, is metabolized differently in certain species of animals. To further define the disposition of bupropion, a study was done involving three species, the rat, mouse, and guinea pig, as animal models to evaluate bupropion metabolism. The pharmacokinetic profiles of bupropion and its major basic metabolites, BW 306U and BW A494U, were determined following the ip administration of 40 mg/kg bupropion to these animals. Pharmacokinetic profiles of the parent drug and metabolites from plasma and brain samples were obtained using a liquid chromatographic procedure. Further investigation of the reduced bupropion metabolite BW A494U was carried out by the ip administration of this metabolite to these animals and assaying the plasma and brain samples 90 min after dosing. Analysis of the pharmacokinetic data revealed that the rat quickly metabolized bupropion, but no basic metabolites accumulated. The mouse metabolized bupropion predominantly to BW 306U, whereas the guinea pig converted bupropion to reduced bupropion (BW A494U) as well as BW 306U. Brain/plasma ratios of bupropion among these animals did not vary significantly. However, both metabolites showed dramatic differences in their brain/plasma ratios among these species. When reduced bupropion (BW A494U) was injected, almost 3% of the plasma concentration of BW A494U was determined to be bupropion in the rat. Lesser amounts were converted in the mouse and guinea pig. Therefore, we have demonstrated that distinct differences exist in the metabolism of bupropion in various species of animals. The guinea pig, when compared to the rat or mouse, appears to constitute a model that most closely resembles that of human bupropion metabolism.

Animals↗
PubMedDate not supplied

Exposure misclassification error in studies on prenatal effects of tobacco smoking in pregnancy and the birth weight of children.

Adverse effects of maternal smoking have been mostly identified through epidemiologic investigations that have used questionnaires to assess active and passive smoking. However, unvalidated self-reports of cigarette smoking may bias true estimates of relative risk of smoking-related health outcomes. This report is based on two separate investigations. First, within a molecular epidemiologic study of the relationship between environmental exposures (smoking, air pollution, diet) and developmental impairment, we have compared self-reported tobacco smoke exposure during pregnancy to plasma cotinine measurements in mothers. One hundred and fifty-eight patients from obstetrical wards in Cracow and in Limanowa, Poland were included in the parent study. Biochemically-identified smokers were defined as persons with plasma cotinine levels greater than 25 ng/mL. The data showed that exposure classification based on self-reported smoking status compared with cotinine values was of low sensitivity (52%) but of high specificity (98%). We assessed the effect of this exposure classification error on the association between low birth weight (LBW) and smoking in pregnancy using data from a related epidemiologic study of children's health in Cracow involving 1115 subjects. The odds ratio (OR) estimates for smoking and LBW after adjustment for exposure misclassification error were significantly higher than before adjustment (crude OR = 2.9, corrected OR = 5.1). The estimated attributable fraction (AF(pop)) based on the crude OR amounted to 22%; however, after adjustment it reached 50%. The corresponding values for the attributable fraction in the exposed group (AF(exp)) were 66% and 80%. These results illustrate the value of validating questionnaire responses on smoking during pregnancy against reliable biologic markers.

Adult↗