PubMed Health⌕ Search

Biomedical subjects

F Maffei

Publications and source records attributed to F Maffei.

At least 37 records · Page 2Linked to original sources

Interaction of licorice on glycyrrhizin pharmacokinetics.

The effects of components of aqueous licorice root extract (LE) on the pharmacokinetics of glycyrrhizin (G) and glycyrrhetic acid (GA) were investigated in rats and humans. The aim of this work was to define the role of pharmacokinetics in G toxicity. In the procedure, G and GA were detected in biological fluids by means of recently improved HPLC methods. Significantly lower G and GA plasma levels were found in rats and humans treated with LE compared to the levels obtained with those in which G alone was administered. The pharmacokinetic curves showed significant differences in the areas under the plasma-time curve (AUC), Cmax, and Tmax parameters. The data obtained from urine samples are in agreement with the above results and confirm a reduced bioavailability of G present in LE compared to pure G. This should be attributed to the interaction during intestinal absorption between the G constituent and the several components in LE. The modified bioavailability could explain the various clinical adverse effects resulting from the chronic oral administration of G alone as opposed to LE.

Administration, Oral↗

Bioavailability of glycyrrhizin and licorice extract in rat and human plasma as detected by a HPLC method.

The pharmacokinetic behaviour of glycyrrhizin (1) was investigated in order to evaluate the difference in bioavailability after oral administration of licorice extract (LE) or glycyrrhizin (1) to rats and humans. For this study, two reliable HPLC methods were developed for the dosage of the levels of 1 and of its metabolite, the glycyrrhetic acid (2) in plasma samples. The determinations were carried out by HPLC on a reversed phase column with UV detector (251 nm), after a careful extraction step of 1 and 2 from the biological matrix. These methods afford good accuracy and satisfactory precision and they allow the determination of both compounds at levels as low as 200 ng/ml. The analytical results improved the knowledge of 1 pharmacokinetics, showing a significantly reduced bioavailability, when administered as LE compared to 1 when administered as such.

Animals↗

Murine alpha/beta interferons inhibit benzo(a)pyrene activation and mutagenesis in mice.

In addition to their antiviral and immune regulatory properties, interferons (IFNs) are known to depress hepatic cytochrome P450-dependent metabolism. As many chemical mutagens and carcinogens require bioactivation by the mixed-function monooxygenase (MFO) system in order to be genotoxic, a combined genetic and biochemical approach was used to establish whether IFNs could inhibit the activation of benzo(a)pyrene (BaP) to the ultimate clastogenic metabolite(s) in vivo. Treatment of mice with murine IFN-alpha/beta depressed cytochrome P450 content, as well as ethoxyresorufin O-deethylase activity (EROD), as a probe of class IA1 P450 isozymes, for 24 hrs and delayed the attainment of normal levels to approximately 30 hrs. After IFNs plus BaP treatment, EROD activity showed a reduction up to 70% after 24 hrs with an enhancement in activity at 30 hrs. A positive correlation exists between the rate of inhibition of oxidative BaP hepatic metabolism and inhibition of clastogenic effects in vivo, as scored in the bone marrow chromosome aberration assay.

Animals↗

Formaldehyde: an experimental multipotential carcinogen.

Male and female Sprague-Dawley rats of different ages at the start of the experiments (12 day embryos, and 7 and 25 weeks old) were administered fromaldehyde in drinking water at different doses (2,500 or 1,500, 1,000, 500, 100, 50, 10, 0 ppm). An increased incidence of leukemias and of gastro-intestinal tumors was observed in formaldehyde treated rats. Gastro-intestinal tumors are exceptionally rare in the rats of the colony used. These results, together with the ones obtained by other Authors on rats exposed by inhalation to formaldehyde, indicate that this compound is an experimental multipotential carcinogen. The experimental results presented in this report give scientific support to the epidemiological observation of a higher incidence of leukemias and of gastro-intestinal cancers among the people occupationally exposed.

Animals↗

Double-blind cross-over clinical comparison of two 2'-chloro benzodiazepines: 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (chlordesmethyldiazepam) versus 7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one (lorazepam) in neurotic anxiety.

A group of 20 female neurotic inpatients has been treated with 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one-(chlordesmethyldiazepan)- 7-chloro-5(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one (lorazepam) according to a double-blind cross-over design. For each drug clinical evaluations were performed by means of Hamilton's rating scale for anxiety states and of Overall and Gorham's brief psychiatric rating scale, at the beginning, after the first week and at the end of the two-week period of treatment, in opposite sequence. A statistically greater efficacy of chlordesmethyldiazepam in comparison to lorazepam was observed. Results are discussed with regard to benzodiazepine structure-activity relationships.

Adult↗