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Biomedical subjects

M Nardini

Publications and source records attributed to M Nardini.

102 records · Page 6Linked to original sources

Dehalogenation and N-dealkylation of chlorpromazine as revealed by plasma concentrations of metabolites in a population of chronically medicated schizophrenics.

Dehalogenaton and N-demethylation of chlorpromazine (CPZ) were studied in twelve psychotic inpatients orally treated for four weeks with a daily CPZ dose of 6.4 +/- 1.1 (S.E.) mg/kg body weight (1.5-14.1, range). Weekly drug and metabolite plasma concentrations were measured by a gas liquid chromatography-nitrogen/phosphorus detector method (GLC/NPD). Plasma concentrations of the parent compound CPZ, of the dehalogenated metabolite promazine (PZ) and of the N-dealkylated metabolites N-monodemethylated chlorpromazine (CPZ-nor1) and N-didemethylated chlorpromazine (CPZ-nor2) had already reached a steady state by the end of the first week of treatment. During the entire treatment period the major plasma component was found to be PZ. Patients (N = 6) on a low dose regimen (3.7 +/- 0.2 mg/kg body weight) showed significantly lower mean plasma concentrations of CPZ and nor metabolites than patients (N = 6) on a higher dose regimen (8.6 +/- 0.7 mg/kg body weight). PZ mean plasma concentrations, however, were not significantly different in the two groups of patients, indicating that the yield of the CPZ dechlorination pathway, as opposed to that of the N-demethylation pathway, was already maximal at the CPZ concentrations attained under the low dose regimen. Male patients (N = 5) exhibited significantly higher mean PZ plasma concentrations over the 4 week period of the study than female patients (N = 7).

Adult↗

Acute sublingual nifedipine and adrenergic activation: a chronobiologic attempt of optimized administration in healthy subjects.

Nifedipine has been shown to increase heart rate and plasma catecholamines, due to an adrenergic activation. Two healthy male subjects, after a period of sinchronization, have self-measured heart rate (HR) every 30 min for two consecutive days through a portable, non invasive, automatic device. The data were then analysed by means of chronobiologic procedures, to verify their personal HR acrophase. Forty-eight hours later, the same subjects repeated the trial, assuming 20 mg of sublingual nifedipine just one hour before their calculated HR acrophase, and data were analysed at the same way. After drug assumption, both HR acrophases and mesors failed to show any modification.

Administration, Sublingual↗

Promazine. A major plasma metabolite of chlorpromazine in a population of chronic schizophrenics.

N-Demethylation and dehalogenation of chlorpromazine (CPZ) were compared in six psychotic inpatients and in rats orally treated for 4 weeks with a daily CPZ dose of 5.4 (mean value) and 20 mg X kg-1 body weight, respectively, by measuring drug and metabolite plasma levels by means of a gas-liquid chromatography-nitrogen/phosphorus detector method. In patients the major plasma metabolite was found to be promazine (PZ), as identified by capillary GC-MS analysis. In rats, on the contrary, PZ represented only a small proportion of the compounds detected in plasma. The mean [PZ]/[CPZ] ratio after 4 weeks of treatment was 1.64 in patients and 0.08 in rats. The relative frequency of the N-demethyl metabolites in plasma, however, was similar in the two species. The mean [N-monodemethylated CPZ]/[CPZ] and [N-didemethylated CPZ]/[CPZ] ratios after 4 weeks of treatment were 0.45 and 0.24 in patients and 0.56 and 0.25 in rats, respectively. These findings suggest that dechlorination of CPZ in psychotic patients represents an important metabolic pathway.

Adult↗

Detection and determination of cysteamine at the nanomole level.

Cysteamine determination is performed by using a coupled enzymatic system. The reaction product between cysteamine and bromopyruvate inhibits competitively and specifically D-amino acid oxidase activity. A reaction system allowing the quantitative assay of cysteamine at the nanomole level has been worked out. The standard curve is linear and the assay is useful in determining the cysteamine concentration in tissues and biological samples. The method is fast and of simple execution. The cysteamine concentration in several mammalian organs is also reported.

Amidohydrolases↗

[Piribedil in the treatment of Parkinson disease (author's transl)].

Seventeen patients with either Parkinson's disease or post-encephalitic parkinsonism were treated with Piribedil, an apomorphine-like drug, in single blind conditions for a period ranging from five weeks to twenty-four months. The analysis of the results shows that Piribedil modifies the extrapiramidal symptomatology being specially effective against the tremor either when used alone or in association with L-Dopa. The side effects noticed during treatment with Piribedil are similar to those of Apomorphine, and are dose-dependent.

Aged↗