P170-related multidrug resistance. Enhancement of idarubicin content in leukemic cells with cyclosporin in vivo: a report of two cases.
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Biomedical subjects
Publications and source records attributed to M Baraldo.
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After informed consent was obtained and with the approval of the Local Ethical Committee, cyclosporine A (CsA) kinetics was studied in 63 psoriatic patients by giving them 2.5 mg/kg CsA orally. In order to calculate oral bioavailability, F, 22 patients were given the same dose i.v. Values of the calculated kinetic parameters were oral F = 22-63%; half-life, t1/2 beta, = 11.05-13.70 h; volume of distribution, Vd, = 4.00-5.02/L/kg; total body clearance, Cl, = 4.25-4.14 ml/min/kg. The area under the blood concentration time curve was more closely related to the dose (r = 0.66) than were trough levels (r = 0.52). No significant relationship was observed between the kinetic parameters studied and the age of the patient.
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OBJECTIVE: To determine the effects of stress hormones on insulin-like growth factor 1 (IGF-1). METHODS: Insulin induced hypoglycemia (< 3 mmol/l) and clonidine induced depression of noradrenergic tone were used to assess the acute effects of cortisol, human growth hormone (hGH), and norepinephrine (NE). RESULTS: Despite the increase of hGH during hypoglycemia, a statistically significant decrease of IGF-1 was observed along with the expected rise of cortisol and NE. To eliminate the role played by NE, NE tone was depressed by administering clonidine. A statistically significant decrease of IGF-1 was also observed. CONCLUSION: Acute cortisol release or a NE decrease induce low IGF-1 levels.
The paper reports plasma levels of levodopa (LD), its main metabolites [dopamine, dihydroxyphenylacetic acid, homovanillic acid, 3-O-methyldopa (3-O-MD)] and carbidopa in 14 parkinsonian patients first treated with Sinemet and thereafter with Sinemet-CR4. A good relationship was observed between LD plasma levels and pharmacological effects. While the LD area under the curve increased after Sinemet-CR4, the same was not observed with metabolites, except with 3-O-MD. The experiments in volunteer subjects confirmed the increase in 3-O-MD in plasma after Sinemet-CR4. Higher levels were observed also in the CSF with a reduction of LD concentrations. This seems to corroborate the hypothesis of an interference with LD passage through the blood-brain barrier in humans.
The pharmacokinetics of chlorpromazine after intravenous infusion were studied in 25 children. The pharmacokinetic parameters studied are markedly different from those reported for adults. A clear relationship was demonstrated between age, serum terminal half-life (r = 0.75) and systemic clearance (r = -0.43). It appears that the pharmacokinetics of chlorpromazine are more rapid in children than in adults.
Pharmacokinetics of single dose (25 mg i.m.) of imipramine was studied in geriatric and young adult patients with mood disorders requiring antidepressant treatment. Imipramine and its principal metabolites were determined by means of a high performance liquid chromatography method with electrochemical detection. Serum concentrations analysis was performed according to a bicompartmental open model. A relationship between age and kinetic parameters such as area under the curve, elimination phase constant, half-life and total body clearance was observed. Significant differences were demonstrated between elderly and young adult patients when comparing these parameters. It is concluded that geriatric patients treated with imipramine should receive doses of about 60% of those of young adults.
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