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Biomedical subjects

S Garattini

Publications and source records attributed to S Garattini.

At least 541 records · Page 30Linked to original sources
PubMedDate not supplied

The case of GISSI in changing the attitudes and practice of Italian cardiologists.

This report first describes the efficiency achieved by a large scale clinical trial (GISSI), which is widely recognized as having made an important contribution to the therapy of AMI, and second emphasizes how a comprehensive research project based upon an innovative clinical trial methodology can influence the attitude and the scientific productivity of a professional community operating within a national health system. To understand the methodology of GISSI, one must appreciate both the cultural and institutional setting in which the first GISSI trial took place as well as the strong economic and scientific expectation surrounding the second GISSI trial.

Attitude of Health Personnel↗
PubMedDate not supplied

Kinetics and brain uptake of S 9795, a new xanthine derivate, in rats.

The relationships between plasma and brain concentrations of S 9795 and its main metabolites after single intravenous doses of S 9795 were examined in rats by high-performance liquid chromatography with UV detection. S 9795 disappeared from plasma and brain almost in parallel, with comparable elimination t1/2 of about 0.8 h, regardless of the dose administered. The volume of distribution was high (about 3 1/kg) but total clearance was also high (about 40 ml/min/kg) and this explains the relatively short plasma and brain t1/2 of the drug in the rat. Among the possible metabolites examined, the N-dearylated metabolite S 10238 rapidly appeared in both plasma and brain. Thereafter, S 10238 was likewise eliminated in parallel from both compartments, although at a slower rate (t1/2 of about 1.4 h) than its parent compound. Norcyclizine, a metabolite resulting from cleavage of the parent drug side-chain, was detected only in the brain and only at the highest dose tested. The brain AUC to plasma AUC ratio was slightly less than 1 for S 9795, about 0.1 for S 10238 and possibly more than 2 for norcyclizine, this latter being present in rat plasma at concentrations below the limits of sensitivity of the method (0.08 nmol/ml). The results indicate that S 9795 and some of its metabolites enter the central nervous system, although to different extents, and support the hypothesis that the lack of central effects of S 9795 is probably the consequence of the poor adenosine brain receptor antagonism by this compound.

Animals↗
PubMedDate not supplied

Effect of phenobarbital on cyclophosphamide cytotoxic activity and pharmacokinetics in mice.

The interaction between cyclophosphamide (CPA) and phenobarbital (PB) was investigated in B6D2F1 mice, checking both the antileukemic and immunosuppressive activity together with the serum levels of CPA and its metabolites. A reduced cytotoxic activity of CPA has been observed when PB is given for 2 days before CPA and an interval of at least 6 hours elapses between the last treatment of PB and the administration of CPA. On the contrary, when PB is given simultaneously with CPA for 2 or 4 consecutive days, an increased antileukemic activity of CPA occurs. In the experimental condition where PB decreases the activity of CPA, serum levels of CPA, assayed by means of a new specific gas-chromatographic method, and of its NBP-alkylating metabolites, indicate that this effect may be explained on a pure pharmacokinetic basis. However, for the situation where an increased effect of CPA was observed under the influence of PB, pharmacokinetic data did not provide a clear explanation.

Animals↗
PubMedDate not supplied

Clinical pharmacokinetics of diazepam.

Diazepam is still one of the most used of the benzodiazepine group of drugs. Extensive studies over 10 years have defined a fairly complete profile of its kinetics. Minor aspects relating to patterns of its metabolism and excretion in certain age groups and in some disease states remain to be described quantitatively. However, there is more than sufficient kinetic information available for the requirements of good clinical practice. For optimum clinical benefit with minimum side-effects the following kinetic properties should be borne in mind: (a) there is a large interindividual variation (up to 30-fold) in dose/blood level ratios, especially when treatment is short-term; (b) the elimination half-life is prolonged in the elderly and the newborn and in some cases of liver disease; (c) there is accumulation of the active N-desmethylated metabolite during long-term treatment; and (d) administration of diazepam to pregnant women leads to rapid distribution from the maternal to fetal compartment: accumulation of both diazepam and desmethyldiazepam could cause prolonged sedation in the newborn. As there does not appear to be any clear relationship between the concentration of diazepam in the plasma and clinical effect, measurement of blood levels, other than for research purposes, is unnecessary. Based on kinetic data, a single administration of diazepam at night should be adequate for hypnotic and anxiolytic effects in most patients.

Adipose Tissue↗
PubMedDate not supplied

Active drug metabolites. An overview of their relevance in clinical pharmacokinetics.

This review underlines the importance of considering in the overall evaluation of drug effect and efficacy not only the kinetics and activities of the administered drug, but also those of the chemical species (metabolites) which are formed in the body. The circumstances in which a role for active drug metabolites may be suspected are described, and a number of specific examples are given. Four different categories are described: drugs which are inactive precursors of active metabolites (e.g. DOPA and cyclophosphamide); active metabolites which contribute to the duration of action of the parent compound (e.g. hexamethylmelamine and clobazam); active metabolites showing a mechanism of action different from that of the parent compound (e.g. buspirone and 1-pyrimidinyl piperazine; fenfluramine and norfenfluramine); and active metabolites showing an antagonistic effect on the activity of the parent drug (e.g. trazodone and m-chlorophenyl-piperazine; aspirin and salicylate).

Anti-Anxiety Agents↗
PubMedDate not supplied

[Exposure to neurotoxic metals and prevalence of parkinsonian syndrome in the area of Brescia].

The prevalence of parkinsonian syndromes was studied in the province of Brescia (Northern Italy), in order to verify its possible increase in the surroundings of ferroalloy plants located in a valley of the pre-Alps. A case-list of subjects affected by these disturbances was identified using four different sources of information: a) registers from local medical clinics; b) admission charts from local hospitals; c) consumption of levodopa; d) NHS list of exemption from prescription payment, due to the illness. Exploratory data show a frequency of parkinsonian disturbances among the residents in the surroundings of the ferroalloy plants and downwind (crude prevalence = 358/100,000 population, standardized for age and sex = 438) significantly higher (s.m.r, = 1.58; C.I. = 1.41-1.76) than the entire Province (crude prevalence 246/100,000). This preliminary result could indicate the interaction of prolonged environmental exposure to heavy metals, such as manganese, and genetic factors, potentially relevant in this mountain population.

Adolescent↗
PubMedDate not supplied

[Pharmacokinetics of fenazepam and its metabolite 3-oxyfenazepam in animals of different species and in man].

It has been established that phenazepam is rapidly absorbed from the gastrointestinal tract of animals and man. The maximal concentrations of the unchanged drugs are reached 1, 0.5, 2 and 4 hours in rats, dogs, cats and man, respectively. The half-life of phenazepam in animal and human blood decreases in the following order: man greater than cat greater than dog greater than rat. The metabolite 3 + hydroxyphenazepam was identified in appreciable amounts in cat and rat blood.

Animals↗