Biomedical subjects

R Farinotti

Publications and source records attributed to R Farinotti.

At least 91 records · Page 5Linked to original sources

PubMed1994

Interactions of cimetidine and ranitidine with aluminum-containing antacids and a clay-containing gastric-protective drug in an "artificial stomach-duodenum" model.

Interactions of cimetidine and ranitidine with aluminum-containing antacids and clay-containing gastric-protective drugs were analyzed in vitro by using an artificial stomach-duodenum model. The model reproduced near-physiologic conditions, taking into account gastric and duodenal flux variations and interactions between gastric mucosa and drugs added to the gastric content. Clay bound cimetidine in acid medium, but the drug was released when the pH increased, resulting in cimetidine amounts in the duodenal site close to those in controls. In contrast, clay bound ranitidine in acid medium and did not release it in the duodenal site. Aluminum-containing antacids did not significantly modify the amount of cimetidine or ranitidine available for absorption. Several factors play a role in the interactions of cimetidine and ranitidine with aluminum-containing antacids and clay-containing gastric-protective drugs: the structure of the antisecretory drugs, gastroduodenal pH, interactions of the antacid and clay with the gastric mucosa, and release of aluminum that could adsorb the drugs or prevent their adsorption by the mucosa. These phenomena are intricate and difficult to analyze without using a physicochemical approach.

Aluminum↗

PubMed1994

Whole blood concentrations of mefloquine enantiomers in healthy Thai volunteers.

We studied the pharmacokinetics of the enantiomers of mefloquine in whole blood in healthy Thai volunteers after administration of a single oral dose of 750 mg of the racemic mixture. Mefloquine pharmacokinetics were stereoselective. The peak concentrations and areas under the curve of the (-) enantiomer were significantly higher than those of its antipode (0.79 versus 0.46 microgram.ml-1 and 402 versus 94 micrograms.h.ml-1). The half-lives of (-)MQ were significantly longer than those of (+)MQ (531 versus 206 h). No stereoselectivity was observed for tmax values.

Adult↗

PubMed1994

Plasma concentrations of the enantiomers of halofantrine and its main metabolite in malaria patients.

The plasma concentrations of the enantiomers of halofantrine and its N-desbutyl metabolite in six patients with malaria were measured after oral administration of 3 x 750 mg doses of micronised, racemic halofantrine hydrochloride given at 6-hour intervals. Significant differences were observed between the plasma concentrations of the enantiomers both of halofantrine and its N-monodesbutyl metabolite. AUC(0)84h values were higher for (+)halofantrine (9917 micrograms.ml-1.h) than for (-)-halofantrine (6127 micrograms.ml-1.h). The clinical significance of these observations is not known. The isomers have equipotent activity in vitro but their relative toxicity has not yet been assessed.

Adult↗

PubMed1994

[Physicochemical interactions and mode of storage of Diprivan].

Only few publications consider physio-chemical interactions and stability of propofol. On the basis of current experience, this agent is safe for use in polypropylene or polypropylene/polystyrene syringes, diluted 1 in 5 in 5% dextrose if necessary. The potential hazards are as follows: 1. Propofol may undergo oxidation when not stored under nitrogen, or when in contact with oxidizing agents (active ingredients or excipients of other preparations). 2. The emulsion may be destabilised by contact with mineral or organic cations (calcium, magnesium, dibasic amino acids etc.) or acids (citric acid etc.). 3. Losses of propofol may occur by adsorption-diffusion (surface adherence combined with penetration of plastic material) during storage in PVC bags or during administration by means of PVC infusion sets. Most of these hazards have still to be evaluated under controlled conditions.

Drug Interactions↗

PubMed1994

Does tolerance develop to the anaesthetic effects of propofol in rats?

We have studied the development of tolerance to the anaesthetic effects of propofol in rats. In the first set of experiments, three groups of rats (A, B and C) received i.v. propofol 10 mg kg-1, 15 mg kg-1 and 20 mg kg-1, respectively. The durations of anaesthesia were recorded, the rats were killed and blood was collected to measure the concentrations of propofol. In a second set of experiments, rats received propofol 10 mg kg-1 i.v. repeated 24 h (group D), 48 h (group E) or 72 h (group F) later. Sleeping times were recorded after the first and the second administration and concentrations of propofol at awakening were measured after the second dose, when rats were killed. Sleeping times were significantly longer in groups B (22.4 min) and C (25.9 min) compared with group A (13.7 min) (P < 0.001 for both). Durations of anaesthesia in groups D, E and F were 14.7, 14.5 and 14.3 min, respectively, after the first dose of propofol and 11.6, 12.1, and 14.9 min, respectively, after the second dose. The rats in groups D and E exhibited shorter sleeping times after the second dose of propofol than after the first (P < 0.01 for both). Concentrations of propofol at awakening did not differ between groups A, B and C or between groups D, E and F. The results suggest lack of changes in susceptibility of the CNS to the anaesthetic effects of propofol.

Anesthesia, General↗

PubMed1994

The intestinal elimination of ciprofloxacin in the rat.

The transepithelial intestinal elimination of ciprofloxacin was studied in a rat model. Two jejunal and one ileal segment, along with their intact blood supplies, were isolated and continuously perfused. Following a single parenteral administration of 25 mg/kg ciprofloxacin, the drug in amounts of 1.97 +/- 0.70, 1.88 +/- 0.99, and 1.44 +/- 0.77 micrograms/cm2 of mucosal surface was recovered over 90 min from the proximal and distal jejunal loops and the ileal loop, respectively, reaching a calculated fraction of 6%-7% of the dose eliminated in the entire small intestine. The rate of intestinal elimination related linearly to the parenteral dose. In the proximal jejunum, however, doses > 25 mg/kg were not accompanied by a concomitant increase in the eliminated fraction, suggesting a saturable transport process. Parenterally administered probenecid, amoxicillin, and nifedipine and changes ranging from 6.0 to 8.5 in the pH of the perfusates did not alter transepithelial elimination. This pathway of elimination of ciprofloxacin may play an important role in curing intestinal infections.

Amoxicillin↗

PubMed1994

Activity of isepamicin and selection of permeability mutants to beta-lactams during aminoglycoside therapy of experimental endocarditis due to Klebsiella pneumoniae CF104 producing an aminoglycoside acetyltransferase 6' modifying enzyme and a TEM-3 beta-lactamase.

The pharmacokinetics and efficacy of isepamicin were compared with those of amikacin and gentamicin in a rabbit model of endocarditis due to Klebsiella pneumoniae CF104 producing beta-lactamase TEM-3 and aminoglycoside acetyltransferase AAC(6')-IV. Only isepamicin and gentamicin, alone or combined with ceftriaxone, were effective as determined by titration of viable bacteria in vegetations. Variants highly resistant to ceftriaxone without change in MICs of aminoglycosides were isolated at the end of each therapeutic regimen except with the most effective one (ceftriaxone plus gentamicin). Examination of the bacterial outer membrane proteins as well as the 50% inhibition of the beta-lactamase activity in intact and sonified cells suggested a permeability defect as being responsible for the increased MICs of ceftriaxone. The activity of isepamicin was superior to that of amikacin against the TEM-3-AAC(6')-IV-producing strain. The combination of gentamicin plus ceftriaxone was the most effective regimen in terms of efficacy and prevention of emergence of resistant strains. Suboptimal aminoglycoside monotherapy might be responsible for selection of permeability mutants to beta-lactams.

Acetyltransferases↗

PubMed1994

Conditions for the emergence of resistance to cefpirome and ceftazidime in experimental endocarditis due to Pseudomonas aeruginosa.

The conditions for the emergence of resistance to cefpirome and ceftazidime were studied in rabbits with experimental aortic endocarditis due to Pseudomonas aeruginosa. The MIC of cefpirome was 16 mg/L and that of ceftazidime was 4 mg/L. Resistant mutants with MICs of > or = 64 mg/L were obtained in vitro to cefpirome after a single passage and to ceftazidime after five passages. A single dose of 50 mg/kg intramuscularly gave mean peak serum concentrations of 110.0 +/- 31.7 mg/L for cefpirome compared with 67.7 +/- 21.4 mg/L for ceftazidime and the half-lives were 1.2 +/- 0.1 h and 2.1 +/- 0.4 h, respectively. After treating infected rabbits for 4 days with various dosing regimens, resistant strains were only detected in those animals in which the time that the serum concentration exceeded the MIC was less than half of the dosing interval. There was no evidence of emergent resistance when the serum concentrations exceeded the MIC for a longer period nor when amikican was combined with the cephalosporins on the first day of therapy. Moreover, once differences in MICs and pharmacokinetics were taken into account, both antibiotics had a similar propensity to induce resistance.

Animals↗

PubMed1994

In vitro renal toxicity and in vivo therapeutic efficacy in experimental murine cryptococcosis of amphotericin B (Fungizone) associated with Intralipid.

We compared the experimental toxicities and activities of deoxycholate amphotericin B (d-AmB) dissolved in glucose (Dd-AmB) or mixed with 20% Intralipid (ILd-AmB). In vitro, ILd-AmB against renal tubular cells in primary culture. In vivo, the toxicities and activities of Dd-AmB and ILd-AmB were studied in DBA2 mice with cryptococcosis. The maximum tolerated dose of intravenously administered d-AmB, i.e., the dose that induced less than 15% mortality because of toxicity, was 1.7 to 2.5 times higher when it was administered as ILd-AmB than when it was administered as Dd-AmB. Both treatments given intravenously at the same dose were equivalent for improving the survival of mice and reducing CFU counts in infected tissue, but at maximum tolerated doses, ILd-AmB (2 mg/kg of body weight) was more effective than Dd-AmB (0.8 to 1.2 mg/kg). AmB concentrations in spleen, liver, lung, and kidney were measured by high-pressure liquid chromatography 4 and 24 h after a single injection of 1.2 mg of Dd-AmB per kg, 1.2 mg of ILd-AmB per kg, or 2 mg of ILd-AmB per kg. In a given organ, AmB levels were similar after administration of 1.2 mg of Dd-AmB or ILd-AmB per kg but were significantly higher after administration of 2 mg of ILd-AmB per kg. The lower level of toxicity of ILd-AmB might be explained by circular dichroism experiments, showing that ILd-AmB contained 10-fold less soluble oligomeric AmB, which is believed to be the toxic form of the drug, than Dd-AmB. We conclude that ILd-AmB is as efficient as Dd-AmB and is better tolerated than Dd-AmB in mice with experimental cryptococcosis. By allowing higher doses of AmB to be infused, Intralipid enhances AmB concentrations in infected sites, and thus the therapeutic activity of the drug.

Amphotericin B↗

PubMed1994

Study of the distribution of oral ciprofloxacin into the mucosa of the middle ear and the cortical bone of the mastoid process.

This multicentre study evaluates the distribution of ciprofloxacin into the tissue structures of the middle ear following multiple dosing of one 500 mg tablet every 12 h. The samples were taken perioperatively from adult patients due to undergo surgery for chronic otitis. Administration of ciprofloxacin was instigated 9 days prior to the operation. The samples were taken at different intervals after the last dose in order to evaluate variations in concentration with time. The average peak concentrations recorded and the time taken to reach these concentrations were as follows: middle ear mucosa (n = 16): 5.54 +/- 3.46 micrograms/g (3-4 h): cortical bone of the mastoid process (n = 21): 1.07 +/- 1.29 micrograms/g (4 h). The measurements carried out 12 h after the last dose show that concentrations of ciprofloxacin in the middle ear mucosa were still at least as high as the minimum inhibitory concentration for this antibiotic for most of the pathogens implicated in acute exacerbations of chronic otitis. These results suggest that, administered as an oral dose of 500 mg every 12 h, ciprofloxacin may be an effective agent for the treatment of chronic suppurative otitis. These results now need to be backed up by clinical trials.

Administration, Oral↗

PubMed1994

Clinical efficacy and pharmacokinetics of micronized halofantrine for the treatment of acute uncomplicated falciparum malaria in nonimmune patients.

Twenty-eight nonimmune patients with acute uncomplicated falciparum malaria returning from subSaharan Africa were treated with a micronized formulation of halofantrine hydrochloride (three doses of 250 mg at 6-hr intervals) to investigate the drug's efficacy, tolerance, and pharmacokinetics. In vitro drug susceptibility patterns were determined by the isotopic semimicrotest. Twenty-four of 28 patients were cured. Two of the four patients experiencing recrudescence were associated with low absorption of the drug and parasites susceptible in vitro to halofantrine. The other two patients had adequate plasma concentrations of halofantrine and its main human metabolite, N-desbutylhalofantrine, but the isolates were also resistant in vitro to the drugs, suggesting drug resistance as the cause of treatment failure. Only mild, transitory side effects were noted. A wide interindividual variation in plasma concentrations of halofantrine and its metabolite was observed. Pharmacokinetic studies suggested that the micronized formulation of halofantrine hydrochloride may not increase drug absorption considerably. Further studies using higher doses or longer treatment periods are needed to ensure that adequate plasma concentrations of the drug are used.

Acute Disease↗

PubMed1994

Safety of pentamidine prophylaxis for Pneumocystis carinii pneumonia on the endocrine pancreatic function in HIV patients.

We assessed the pancreatic beta cells function of HIV patients receiving either 300 mg per month of aerosolized pentamidine (n = 12) or oral trimethoprim-sulfamethoxazole (TMP-SMX), twice a day three times per week (TMP: 160 mg, SMX: 800 mg) (n = 10). Intravenous (i.v.) glucose tolerance tests were performed after i.v. injection of 0.5 glucose by kg of body weight in 30 seconds. Plasma insulin levels were assessed at baseline, 1, 2, 3 and 5 min. Moreover, in patients receiving inhaled pentamidine, plasma glucose amylase and insulin levels were measured every 30 min for 2 hours after the end of the aerosol. Plasma pentamidine levels were measured 30 min after the end of the aerosol. Those tests were performed every 2-3 months for one year. In most patients taking aerosol treatment, pentamidine levels were detectable, remaining under levels of 50 ng/ml. Pentamidine plasma levels increased in a time dependent manner. Baseline plasma glucose, amylase and insulin levels were in normal range and remained stable during the therapy. For 7 out of 12 patients, glucose tolerance tests showed an adequate insulin secretion: the addition of the two best insulin levels were higher than 70 IU/ml. When this criteria was not found (n = 5), a glucagon stimulation test allowed to exclude an endocrine pancreatic dysfunction. Due to its apparent short half-life, increased pentamidine levels could be related to an improvement of spray techniques as well as to a cumulative effect. Pancreatic function was preserved in pentamidine-treated patients compared to TMP-SMX-treated patients.

AIDS-Related Opportunistic Infections↗

PubMed1994

In vitro activity of the enantiomers of N-desbutyl derivative of halofantrine.

The in vitro activity of the enantiomers of N-desbutylhalofantrine, the major human metabolite of halofantrine, was compared using the semi-microtest against the multidrug-resistant Plasmodium falciparum FCM 29/Cameroon clone. The mean 50% inhibitory concentration (IC50) values (+/- standard deviation) of the enantiomers were equivalent (2.07 +/- 0.41 and 1.70 +/- 0.33 nmol/L). The enantiomers of the metabolite of halofantrine, as well as those of the parent compound, have the same antimalarial activity. Since (+)-halofantrine and enantiomer-1 of the metabolite attain higher plasma concentrations in man, our study suggests that these enantiomers may be more active in vivo.

Animals↗

PubMed1994

[Luminescence and detection in liquid chromatography: III. Chemiluminescence].

Chemiluminescence avoiding the fluctuations of the light of excitation, Rayleigh and Raman scattering, allows to get detection threshold 100 to 1,000 times lower than fluorimetry. Processes using the luminol, lucigenin, aryloxalic esters and ozone are employed in liquid chromatographic detection. Some pharmaceutical, biological and toxicological examples illustrate their applications.

Acridines↗

PubMed1993

Improved column-switching liquid chromatographic method for the determination of the enantiomers of mefloquine.

A liquid chromatographic method for the determination of the enantiomers of mefloquine has been improved. The chromatography involved two columns: an achiral cyanopropyl stationary phase for the quantification of (+/-)-mefloquine and a chiral naphthyl-urea stationary phase for the determination of the enantiomeric ratio. Compared with the previous method, which needed two detectors, this one used one detector-integrator to which the two columns are connected alternately by an automated column-switching system. The method is suitable for the quantification (0.05 microgram/ml) of mefloquine and the determination of enantiomeric ratios from 500-microliters plasma samples with ultraviolet detection.

Chromatography, Liquid↗

PubMed1993

Determination of the enantiomers of zopiclone and its two chiral metabolites in urine using an automated coupled achiral-chiral chromatographic system.

The enantiomers of zopiclone and its two chiral N-desmethyl and N-oxide metabolites were determined in urine using a coupled achiral-chiral liquid chromatographic method. After liquid-liquid extraction, zopiclone and its two metabolites were quantified on a cyanopropyl column. After fluorimetric detection on the achiral system, the eluent was switched through a silica precolumn in order to trap and concentrate the analytes. Each fraction was then backflushed separately onto a carbamate cellulose chiral stationary phase in order to determine the enantiomeric ratios. The coupled system was automated with an autosampler and a switching valve programmed by an integrator. The method was validated, and a first trial was performed on urine samples of a volunteer treated with 15 mg of racemic zopiclone.

Azabicyclo Compounds↗

PubMed1993

Influence of specific albumin ligand markers used as modifiers on the separation of benzodiazepine enantiomers by chiral liquid chromatography on a human serum albumin column.

Specific ligand markers for the various binding sites of human serum albumin (HSA) have been described in the literature. Some of these markers (medium chain fatty acids, warfarin, digoxin, and bilirubin) were used as mobile phase modifiers. Using a high performance liquid chromatographic (HPLC) column containing HSA as stationary phase, their influence was investigated on the separation in this phase of the enantiomers of three benzodiazepines (temazepam, oxazepam, and lorazepam). Displacement effects were observed with medium chain fatty acids. This influence was proportional to the chain length and to the concentration of acid. Allosteric cooperative effects were noted with digoxin for the three benzodiazepines. Both displacement and cooperative effects were observed with warfarin. Stereoselectivity was decreased for temazepam and oxazepam and increased for lorazepam.

Anti-Anxiety Agents↗

PubMed1993

Killing kinetics of cefuroxime against Streptococcus pneumoniae in an in vitro model simulating serum concentration profiles after intramuscular administration.

The killing kinetics of cefuroxime against 25 Streptococcus pneumoniae isolates with penicillin MICs of < 0.1, 0.1-1.0 and 2 mg/l were studied in an in vitro model simulating the serum concentration profile in healthy adults following a single intramuscular injection of 500 mg. Cefuroxime was bactericidal against the isolates with exquisite or slightly diminished susceptibility to penicillin (-4 and -3.9 log10 cfu/ml killing, respectively) during the 6 h incubation period. In contrast, there was only a 2.8 log10 cfu/ml reduction in the initial inoculum of six of the eight isolates resistant to penicillin (MIC 2 mg/l). The two remaining penicillin-resistant isolates (cefuroxime MIC 8 mg/l) only showed a 2 log10 cfu reduction in the initial inoculum.

Adult↗