Plasma concentrations of risperidone and 9-hydroxyrisperidone: effect of comedication with carbamazepine or valproate.

To evaluate the pharmacokinetic interaction between risperidone and the mood-stabilizing agents carbamazepine and valproic acid, steady state plasma concentrations of risperidone and 9-hydroxyrisperidone (9-OH-risperidone) were compared in patients treated with risperidone alone (controls, n = 23) and in patients comedicated with carbamazepine (n = 11) or sodium valproate (n = 10). The three groups were matched for sex, age, body weight, and antipsychotic dosage. Plasma concentrations of risperidone and 9-OH-risperidone did not differ between valproate-comedicated patients and controls. By contrast, the concentrations of both compounds were lower in patients taking carbamazepine, although the difference reached statistical significance only for the metabolite (p < 0.001). The sum of the concentrations of risperidone and 9-OH-risperidone in patients receiving carbamazepine (median 44 nmol/L) was also significantly lower than in patients receiving valproate (168 nmol/L) and in controls (150 nmol/L). In five patients assessed with and without carbamazepine comedication, dose-normalized plasma risperidone and 9-OH-risperidone concentrations were significantly lower when the patients received combination therapy than when they received risperidone alone. In three patients assessed with and without valproate, no major changes in the levels of risperidone and its metabolite were observed. These findings demonstrate that carbamazepine markedly decreases the plasma concentrations of risperidone and its active 9-OH-metabolite, probably by inducing CYP3A4-mediated metabolism. This interaction is likely to be clinically significant. Conversely, valproic acid does not cause any major change in plasma antipsychotic levels.

[Increase of oxygen free radicals and their derivatives in chemo- and radiation treated neoplasm patients]. / Incremento dei radicali liberi dell'ossigeno e dei loro derivati in pazienti neoplastici chemio- e radiotrattati.

BACKGROUND: Radical oxygen species (ROS) are known to mediate cytotoxic anticancer activity by modifying the cellular homeostatic redox balance. The aim of the study is to evaluate whether cancer patients show more ROS after radio/chemotherapy. METHODS: ROS were evaluated in 32 oncologic untreated patients. Blood samples were collected both before and after the end of radio/chemotherapy. Spectrophotometric detection of ROS was performed by using d-ROMs test (Diacron). RESULTS: After therapy all patients showed a marked increase in ROS (378 +/- 35 U Carr) compared to values measured before therapy (269 +/- 62 U Carr, p < 0.0001). This result was more evident during the first course of therapy. No significant differences were observed between patients who received radio or chemotherapy. CONCLUSIONS: In conclusion both radio and chemotherapy induce oxidative stress by increasing radical oxygen species, exceeding the antioxidative capacities of cancer patients. This is useful for therapeutic purposes but may enhance the cytotoxicity induced by therapy.

A novel HPLC method for the determination of mitoxantrone in pharmaceutical formulations.

An HPLC method, using reversed phase chromatography, for the quantitative determination of mitoxantrone in pharmaceutical formulations has been developed. Rhein has been used as internal standard.

[Behavior of serum sialic acid levels at various stages of neoplastic disease]. / Comportamento del livello sierico dell'acido sialico in momenti diversi della malattia neoplastica.

Serum sialic acid levels were measured at two different stages of neoplasia (active and non-active phases). CEA levels were also assayed at the same time. 98 patients suffering from different neoplastic diseases and a group of healthy controls were studied. Serum sialic acid levels were always significantly higher in the neoplastic patients. When neoplastic disease were divided into active and non-active groups, it was observed that the level of this glycoprotein was specific in the non-active (NA) phase only for breast tumours and lymphomas. Correlation with CEA levels was also significant in these cases. It is concluded that serum sialic acid assay may be useful only for melanomas, breast tumours and lymphomas where the level of this membrane protein undergoes significant changes according to the stage of the tumour.

[Immunohistochemical study on the presence of CEA in primary brain tumors. Preliminary note]. / Studio immunoistochimico sulla presenza del CEA nei tumori cerebrali primitivi. Nota preliminare.

The immuno peroxidase histochemical technique produced optic microscopic evidence of CEA (carcinoembryonic antigen) in 19 out of 42 (42.25%) brain tumours including 12 astrocytomas, 6 glioblastomas and 1 ependymoma. The possibility of identifying CEA in such tumours is extremely interesting in view of the fact that CEA is currently the antigen most commonly studied and utilised in various types of non-cerebral cancers.

[Pathological tolerance to glucose and breast neoplasia]. / Patologica tolleranza al glucosio e neoplasia mammaria.

Thirty non diabetic women with breast cancer and five with benign breast disease have been evaluated by oral glucose tolerance test. 40% showed a diabetic-like curve. The positive women had a metastatic disease. The positive correlation between a pathologic glucose tolerance and the metastatic disease are stressed. The conclusion is drawn that the research of a latent glycidic alteration as monitor of breast cancer evolution is useful.