Search PubMed⌕ Search

Biomedical subjects

M Bonati

Publications and source records attributed to M Bonati.

At least 127 records · Page 7Linked to original sources
PubMed1984

Physicochemical and analytical characteristics of amiodarone.

Data are reported on the analytical and physicochemical characteristics of amiodarone, for use in identifying and/or assaying this antiarrhythmic agent. The drug is highly soluble in chloroform and poorly soluble in water. Its acid-base constant (pKa) is 6.56, and its maximal lipid solubility range is from pH 3.5 to 5.5.

Amiodarone↗
PubMed1984

Pharmacokinetics of teicoplanin in man after intravenous administration.

The pharmacokinetics of teicoplanin, a new glycopeptide antibiotic active against gram-positive aerobic and anaerobic bacteria, was studied in adult male volunteers given 2- and 3-mg/kg doses by a constant-rate 0.5-hr infusion. Serum and urine samples were collected up to 96 hr. Mean peak serum levels after the two doses were 15.7 and 22.4 micrograms/ml. Postinfusion serum teicoplanin levels showed triexponential decay. A three-compartment body model gave close values for pharmacokinetic parameters after the two doses. The mean half-life of the lambda 1 phase was 20.3 min, that of the lambda 2 phase was 2.9 hr, and the half-life of the estimated lambda 3 phase was 40.5 hr, in good agreement with that of the lambda z phase (45.9 hr) calculated from the last urine data. The mean volume of distribution of the central compartment was 0.09 liter/kg and the steady-state volume of distribution using noncompartmental analysis was 0.84 liter/kg. Total clearance averaged 16.05 ml/hr/kg, with renal clearance arbout half this (9.51 ml/hr/kg), calculated by two different methods. The average total recovery of active teicoplanin in urine over 4 days was 52%, suggesting that both renal and nonrenal mechanisms are involved in elimination of the drug. The concentrations of teicoplanin in serum and urine exceeded the MIC (ranging from 0.02 to 2 micrograms/ml) on many pathogenic organisms for at least 1 day after administration.

Adult↗
PubMed1984

Kinetics and bioavailability of N-nitrosodiethanolamine after intravenous and cutaneous administration to rats.

Male CD-COBS rats were given N-nitrosodiethanolamine (NDELA) by intravenous or cutaneous administration at a dose of 5 mg/kg. Blood and liver were analysed for NDELA at various times after administration. The excretion of unchanged NDELA and its acidic metabolite N-(2-hydroxyethyl)-N-carboxymethylnitrosamine (ECMN) was determined in urine for 24 hr after treatment. The semilogarithmic blood concentration-time plot after iv injection showed a triphasic profile indicating that a three-compartment model may adequately describe the kinetics of this compound. After cutaneous application NDELA was rapidly absorbed through the skin, and the absolute bioavailability was calculated to be 27% from blood data, and to be 32% (NDELA + ECMN) from urine data. Hepatic NDELA levels reflected blood levels after both treatments, indicating that this organ does not accumulate NDELA to a significant extent. Urinary excretion of unchanged NDELA after iv and cutaneous administration was 83 and 25% of the administered dose, respectively. ECMN excretion was 4.9 and 2.5% of the administered dose after iv and cutaneous administration, respectively.

Animals↗
PubMed1984

Kinetics of caffeine metabolism in control and 3-methylcholanthrene induced rat liver microsomes.

The kinetics of formation of primary metabolites of caffeine (paraxanthine, theophylline, theobromine and 1,3,7-trimethyluric acid) was studied in control (CO) and 3-methylcholanthrene-induced (MC) rat liver microsomes. Vmax was similar but Km was 16 times lower for total caffeine metabolism in CO and MC microsomes, respectively. Similar behavior was observed in the formation of each metabolite. Single metabolites showed different degrees of induction at non-saturating concentrations of caffeine. Kinetics was non-linear in CO microsomes.

Animals↗
PubMed1984

Plasma levels of salicylate and aspirin in healthy volunteers: relevance to drug interaction on platelet function.

Salicylate can prevent the inhibitory effect of aspirin on platelet cyclooxygenase activity. We investigated whether salicylate and aspirin interact in platelets in humans at doses and plasma levels of clinical relevance. In our first experiment in healthy volunteers, the lowest dose of intravenously administered aspirin that suppressed arachidonate-induced platelet aggregation and serum immunoreactive thromboxane B2 generation was 40 mg. In our second experiment, volunteers given oral doses of sodium salicylate (250 or 1000 mg) had peak plasma salicylate levels averaging 20 and 76 micrograms/ml, respectively. Neither platelet aggregation or thromboxane B2 formation was modified by either salicylate treatment. Forty minutes later, all six volunteers received 40 mg of aspirin intravenously. Aspirin levels were not affected by previous salicylate ingestion, but inhibition by aspirin of both platelet aggregation and thromboxane B2 generation was significantly prevented by the higher salicylate dose. In our last experiment, peak plasma levels of aspirin and salicylate were measured in healthy volunteers after ingestion of either 320 mg of compressed or 800 mg of enteric-coated aspirin. Salicylate levels averaged 19 and 51 micrograms/ml, respectively, after the lower and higher doses of aspirin, whereas aspirin averaged 3 micrograms/ml after either dose. Serum thromboxane B2 generation was almost completely inhibited 1 hour after either aspirin dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

In vitro and in vivo cytotoxicity of possible uracil metabolites of methylxanthines.

The present study was designed to elucidate the cytotoxic potential of 8 possible substituted uracilic metabolites of methylxanthines. 5-Fluorouracil (5-FU) was used as a reference uracil analogue with cytotoxic activity. Substituted uracil derivatives examined in this study did not affect the proliferative capacity of PHA-stimulated rat lymphocytes, murine L1210 leukaemia and rat chondrocytes. Caffeine had some growth inhibitory activity of extremely high concentrations (greater than 100 micrograms/ml). In vivo administration of 6-amino-5[N-methyl-formylamino]1,3-dimethyluracil (1,3,7-TAU) and 6-amino-5[N-acetylamino]3-methyluracil (7-A3-MAU) caused a transient short-lived reduction of L1210 tumour cell numbers. These observations do not appear to support the hypothesis that substituted uracils are involved in the toxicity of high doses of caffeine in rats.

Animals↗
PubMed1983

Acute overdosage of amiodarone in a suicide attempt.

Clinical and biochemical variables and blood levels of amiodarone and its metabolite are reported after acute self-intoxication in a young woman. Despite the huge amount of drug ingested no clinical side effects were documented over the monitored period of 3 months.

Adult↗
PubMed1982

Caffeine disposition after oral doses.

Caffeine (TMX) disposition was studied in mean after 1, 5, and 10 mg/kg in water, as mocha coffee (1.54 mg/kg) and as a soft drink (0.22 mg/kg). TMX and its metabolites were analyzed in plasma and urine by high-pressure liquid chromatography. The design permitted confirmation of most of the partial results in various experimental settings and contributed new data on the metabolic disposition of TMX, with specific reference to main dimethylxanthine metabolite found in plasma, paraxanthine (1,7-dimethylxanthine). Different analysis methods were compared for the calculated parameters (absorption and elimination rate constants and renal clearance)to assess the consistency of results. The kinetics of TMX and of its dimethylated metabolites in plasma were described with a model that used an analogdigital hybrid computing system. In addition to providing a comprehensive profile of TMS disposition in the healthy adult, the results indicate tha TMX exhibits dose-independent kinetics at the levels at which man normally takes TMX.

Administration, Oral↗
PubMed1981

Urinary excretion of an uracilic metabolite from caffeine by rat, monkey and man.

Caffeine (C) metabolism has been studied in rat, monkey (Macaca cynomolgus) and man after oral administration of the compound. Eleven metabolites were quantified in urine; particular attention has been drawn to 4-amino [5-formyl methylamino]1,3-dimethyl uracil (ADMU) because of its structural analogies with 5-fluorouracil. The rat has been found to produce a much larger fraction of ADMU (about 30%) in respect to monkey an man (1-2%). The potential toxicological implications of this findings are discussed.

Adult↗
PubMed1981

Theophylline distribution in the premature neonate.

Theophylline (T) tissue distribution was studied in 11 premature newborns treated with T for prematurity apnea, who had died from severe pathology. To investigate the pattern of distribution of T, in particular the role of the blood-brain barrier in this period of life, two animal species were employed (rat and guinea pig), differing widely in their postnatal development. T was administered to the animals acutely and chronically and the resulting data were compared to human findings. In human prematures no specific accumulation and a wide variety in tissue concentrations, as in tissue/blood ratios, were observed. In the rat, unlike the guinea pig, brain/blood ratios of T concentration declined as postnatal age rose, suggesting that development of the blood-brain barrier plays a major role.

Aging↗
PubMed1981

Theophylline metabolism during the first month of life and development.

The metabolic pathway of theophylline (T) was studied in 12 newborns, one young infant, six children, and three adult volunteers. T was injected IV, and blood and urine samples were assayed for T, caffeine (C), and their metabolites by a high-pressure liquid chromatography technique. We confirmed the methylation of T to C in newborn infants but not in older subjects. Demethylation of T to 3-methylxanthine was found in the young infant, in children, and in adults, but not in newborns. The major products excreted by neonates were T, 1-methyluric acid, and 1,3-dimethyluric acid. Children excreted a larger fraction of methyluric acids than adults. Renal and body clearance of T and C are reported and discussed in relation to the age.

Adult↗
PubMed1980

[2-14C]caffeine metabolism in control and 3-methylcholanthrene induced rat liver microsomes by high pressure liquid chromatography.

Theobromine, theophylline, paraxanthine and 1,3,7-trimethyluric acid were identified as caffeine metabolites after incubation of [2-14C]caffeine with rat liver microsomes and separation by high-pressure liquid chromatography (HPLC). A 9-fold induction of caffeine metabolism was observed in 3-methylcholanthrene (MC)-induced microsomes and this induction ranged from 4 to 11 times for individual metabolites. Induction of aryl hydrocarbon hydroxylase (AHH) was about 5-fold, comparable to that of theophylline formation. Primary caffeine metabolism is an enzymic process catalyzed by the microsomal mixed-function oxidases.

Animals↗
PubMed1978

Kinetics and efficacy of theophylline in the treatment of apnea in the premature newborn.

Aminophylline (theophylline-ethylenediamine) was administered to 27 premature newborns to prevent apneic spells. Of the 22 patients monitored for theophylline concentration, a therapeutic blood level was reached in 19 in 1--2 days, and 3 stayed below it. "Toxic" blood levels (less than or equal to 20 microgram/ml) were reached in 3 cases, one of whom showed signs of toxicity. Theophylline treatment was not efficient in the prevention of apnea when a serious underlying disease was present. Theophylline blood half-life (mean:27.0 h) and clearance (mean 12.9 ml/h/kg) confirmed the slow elimination pattern of the drug in the premature infant.

Apnea↗