Search results for "kinetics"
showing 10 items of 2224 documents
Report on Intrauterine Drug Exposure During Second Trimester of Pregnancy in a Heroin-Associated Death
1999
A 17-year-old girl was found dead in a public toilet with fresh needle puncture marks. She was 18-20 weeks pregnant with a male fetus. Drug screening of her blood and urine indicated recent heroin use. Chronic drug use was confirmed by hair analysis. Amniotic fluid as well as fetal and maternal tissues and body fluids were analyzed by GC/MS and HPLC. All the fetal specimens were investigated, and the following levels of drugs were found: 6-monoacetyl-morphine (blood: 152 ng/g; amniotic fluid: 128 ng/g; brain: 140 ng/g; lung: 110 ng/g; liver: 2 ng/g; kidney: 40 ng/g), morphine (blood: 1360 ng/g; amniotic fluid: 604 ng/g; brain: 710 ng/g; lung: 1030 ng/g; liver: 2060 ng/g; kidney: 1100 ng/g),…
Phase II dose escalation study of caspofungin for invasive Aspergillosis.
2011
ABSTRACT Our objective was to evaluate the maximum tolerated dose of caspofungin for invasive aspergillosis (IA). The safety and pharmacokinetics of escalating dosages of caspofungin were investigated in IA. Eight patients each received caspofungin 70, 100, 150, or 200 mg once a day (QD). Dose-limiting toxicity (DLT) was defined as the same non-hematological treatment-related adverse event of grade ≥4 in 2 of 8 patients or ≥3 in 4 of 8 patients in a cohort. A total of 46 patients (median age, 61 years; 21 female; 89% with hematological malignancies) received caspofungin (9, 8, 9, and 20 patients in the 70-, 100-, 150-, and 200-mg cohorts) for a median of 24.5 days. Plasma pharmacokinetics w…
Antagonistic effects of hypertrehalosemic neuropeptide on the activities of 6-phosphofructo-1-kinase and fructose-1,6-bisphosphatase in cockroach fat…
2001
Hypertrehalosemic neuropeptides from the corpora cardiaca such as the decapeptide Bld HrTH bring about a profound switch in the metabolic activity of cockroach fat body during which production of the blood sugar trehalose is stimulated while the catabolism of carbohydrate (glycolysis) is inhibited. The mechanisms of the metabolic switch are not fully understood. Incubation of isolated fat body from the cockroach Blaptica dubia with 10(-8) M Bld HrTH, for 10-60 min, stimulated glycogen breakdown and increased the content of the substrates of both the glycolytic enzyme 6-phosphofructo-1-kinase (PFK, EC 2.7.1.11) and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBPase, EC 3.1.3.11) in…
Small rises in plasma choline reverse the negative arteriovenous difference of brain choline.
1990
The concentrations of free choline in blood plasma from a peripheral artery and from the transverse sinus, in the CSF, and in total brain homogenate, have been measured in untreated rats and in rats after acute intraperitoneal administration of choline chloride. In untreated rats, the arteriovenous difference of brain choline was related to the arterial choline level. At low arterial blood levels (less than 10 microM) as observed under fasting conditions, the arteriovenous difference was negative (about -2 microM), indicating a net release of choline from the brain of about 1.6 nmol/g/min. In rats with spontaneously high arterial blood levels (greater than 15 microM), the arteriovenous diff…
The neuropeptide calcitonin gene-related peptide differently modulates proliferation and differentiation of smooth muscle cells in culture depending …
2001
Abstract Calcitonin gene-related peptide (CGRP) is a neuropeptide present around vasculature very early during development, when smooth muscle cells (SMC) are still proliferating and not yet totally differentiated. We investigated the effects of CGRP on proliferation and differentiation of SMC in culture; 10 −7 M CGRP added in the medium of cultured smooth muscle cells every 2 days did not significantly changed cells growth rate in 1% FCS. At the opposite, this treatment modulated proliferation of cells grown in 10% FCS medium. Two distinct populations of SMC with different growth rates were obtained from our primary cultures. SMC which proliferated slowly in the presence of 10% fetal calf …
Uptake and storage of choline by rat brain: influence of dietary choline supplementation.
1991
In order to elucidate the regulation of the levels of free choline in the brain, we investigated the influence of chronic and acute choline administration on choline levels in blood, CSF, and brain of the rat and on net movements of choline into and out of the brain as calculated from the arteriovenous differences of choline across the brain. Dietary choline supplementation led to an increase in plasma choline levels of 50% and to an increase in the net release of choline from the brain as compared to a matched group of animals which were kept on a standard diet and exhibited identical arterial plasma levels. Moreover, the choline concentration in the CSF and brain tissue was doubled. In th…
Steady state concentrations of clomipramine and its major metabolite desmethylclomipramine in rat brain and serum after oral administration of clomip…
2000
Twenty male Sprague-Dawley rats received five oral doses of clomipramine 20 mg/kg at 4-h intervals. The animals were decapitated 1, 2, 3, 5 and 12 h after the last dose for determination of clomipramine and desmethylclomipramine in serum and frontal cerebral cortex. Time dependent concentrations of clomipramine and desmethylclomipramine paralleled in serum and brain. Half-lives were similar in serum and brain with 7.8 versus 6.2 h and 5.5 versus 5.0 h for clomipramine and desmethylclomipramine, respectively. Absolute concentrations, however, were markedly higher in brain than in serum - 12.5 fold for clomipramine and 7.4 fold for desmethylclomipramine. The data indicate that serum and brain…
Non-competitive inhibition of clomipramineN-demethylation by fluvoxamine
1995
The selective serotonin reuptake inhibitor fluvoxamine interferes with the metabolism of tricyclic antidepressants. The present investigation was set out to characterize these interactions in vitro using rat liver microsomes and in vivo by analysing levels of clomipramine and metabolites in sera of depressed patients treated concomitantly with fluvoxamine and clomipramine. Clomipramine was N-demethylated and hydroxylated in vitro by microsomes to N-desmethyl-clomipramine, 8-hydroxyclomipramine, and 10-hydroxyclomipramine. Kinetic analyses revealed Km values of 6.2 microM for N-demethylation and 1.2 microM for 8-hydroxylation. Fluvoxamine was a non-competitive inhibitor for N-demethylation w…
The Pharmacokinetics of Metronidazole and Gentamicin in a Single Preoperative Dose as Antibiotic Prophylaxis in Colorectal Surgery
2008
Objective: To describe, in patients undergoing colorectal surgery (CRS), the pharmacokinetics of a single, prophylactic preoperative dose of 1500 mg of metronidazole plus 240 mg gentamicin and measure its efficacy in accordance with the accepted pharmacodynamic and microbiological parameters. Method: Thirty-six patients undergoing CRS agreed to participate in the study. Three blood samples were taken from each. Cmax 15 minutes after finishing the infusion of the mixture, CfinIQ on finishing the surgery, and Cmin between 12 and 24 hours post-administration. The concentrations of metronidazole and gentamicin in each simple were measured and the pharmacokinetic parameters were estimated (dV-di…
Apparent vs real effects of scopolamine on the learning of an active avoidance task.
1996
The effects of scopolamine hydrobromide (0.5 and 2 mg/ kg) administered intraperitoneally to Balb/c male mice before or after training in active avoidance were explored in four training sessions and in a subsequent test session, free of drug. Animals given scopolamine prior to training performed better than controls, an effect that was reversed in the session free of drug. However, a deeper analysis of the data permits us to interpret this increment in the number of avoidance responses as a consequence of the increase in activity produced by the drug and not as learning. In the animals injected with scopolamine after sessions no effects were observed. In conclusion, the results of the prese…