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Biomedical subjects

R Farinotti

Publications and source records attributed to R Farinotti.

At least 127 records · Page 7Linked to original sources

Determination of the enantiomers of mefloquine in plasma and whole blood using a coupled achiral-chiral high-performance liquid chromatographic system.

A coupled achiral-chiral high-performance liquid chromatographic system has been developed for the determination of the enantiomers of mefloquine, (+)-MFQ and (-)-MFQ, in plasma and whole blood. The MFQ was separated from the interfering components in the biological matrix and quantified on a cyano-bonded phase, and the enantiomeric composition was determined on an (S)-naphthylurea chiral stationary phase. The two columns were connected by a switching valve equipped with a silica precolumn. The precolumn was used to concentrate the MFQ in the eluent from the achiral column before backflushing onto the chiral phase. The coupled-column system was validated and applied to the analysis of a pilot study of the pharmacokinetics of (+)- and (-)-MFQ in plasma and whole blood.

Chromatography, High Pressure Liquid↗

Comparison of serum hydroquinidine determination by fluorescence polarization immunoassay and liquid chromatography.

Hydroquinidine is a structural analogue of quinidine. It is used in the treatment and prevention of cardiac arrhythmias and necessitates serum monitoring. Fluorescence polarization immunoassay (FPIA) of quinidine has been proposed and we have tested the performance of this assay for hydroquinidine using its cross-reaction with quinidine. Tracer (quinidine labelled with fluorescein) and anti-serum were purchased from Abbott S.A. Standard curves were obtained using specifically prepared hydroquinidine calibrators and within-run and run-to-run precision values (expressed as relative standard deviation) (RSD) lower than 5.3% (n = 10). In order to evaluate specificity of this assay in the clinical situation, FPIA and liquid chromatography results were compared.

Chromatography, High Pressure Liquid↗

Acebutolol and diacetolol plasma levels in patients undergoing myocardial revascularization with hypothermic cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) has been reported to alter the disposition of numerous drugs and consequently to modify their plasma levels. The present study was designed to delineate the time course of acebutolol (a cardioselective beta-blocker) and diacetolol (its main metabolite) plasma levels in seven patients undergoing myocardial revascularization with hypothermic CPB. All patients were given oral acebutolol twice daily until 3 hours before surgery. Initiation of CPB produced an immediate and significant, but transient, decrease in acebutolol and diacetolol plasma concentrations. Cessation of CPB was not associated with an increase in plasma beta-blocker levels. It is concluded that CPB does not induce major alterations in the time course of acebutolol and diacetolol plasma concentrations.

Acebutolol↗

[Respiratory effects of almitrine on various levels of the fraction of inspired oxygen. A study in the anesthetized dog].

The effects of intravenous almitrine under normoxic, hyperoxic, and hypoxic conditions were studied in 5 male beagle dogs (mean weight 15.2 +/- 5 kg) anaesthetized with thiopentone. Plasma concentrations of thiopentone were maintained constant at 27-29 mg.1(-1). Each animal underwent twice the three different experiments, with a lapse of a fortnight between each experiment: a) breathing room air, with intravenous administration of 1 mg.kg-1 almitrine over 30 s, b) breathing room air, then pure oxygen for 15 min, followed by an intravenous administration of 1 mg.kg-1 almitrine over 30 s with the dog still breathing pure oxygen, and c) breathing room air, then progressively less oxygen (FIO2 0.18, 0.16, 0.14, 0.12 for 5 min each), followed by an intravenous administration of 1 mg.kg-1 almitrine over 30 s with the dog still breathing a mixture with 12% oxygen. Tidal volume, respiratory rate, minute ventilation, inspiratory and expiratory duration, arterial pH, PaO2 and PaCO2 were measured respectively in room air, after 100% oxygen, in hypoxia (FIO2 = 0.12), before, 5 and 10 min after the injection of almitrine. Hyperoxia depressed ventilation (-21%), whilst hypoxia stimulated it (+126%), although significantly less than in the awake animal. Almitrine restored the respiratory response to hypoxia, but hyperoxia did not suppress respiratory stimulation due to the drug. It would therefore seem likely that almitrine acts on peripheral arterial chemoreceptors, but also on other structures. The results of this study suggest that almitrine may be useful in restoring the respiratory response to hypoxia during recovery from anaesthesia.

Almitrine↗

Pharmacokinetics of propofol infusions in patients with cirrhosis.

We have compared the pharmacokinetics of propofol as an infusion in 10 control and 10 patients with cirrhosis. Anaesthesia was induced within 3-4 min during administration of an infusion of propofol 21 mg kg-1 h-1. After 5 min, the infusion was decreased in a stepwise manner to 12 mg kg-1 h-1 and subsequently 6 mg kg-1 h-1. The mean recovery time after discontinuation of the infusion was significantly longer in the cirrhotic group; however, when patients opened their eyes, blood concentrations of propofol were similar in both groups (1 micrograms ml-1). Pharmacokinetic analysis was performed from the beginning of infusion to 8 h after termination. Total body clearance was not reduced significantly in cirrhotic (1.56 (SD 0.48) litre min-1) compared with control (1.75 (0.32) litre min-1) patients. The volume of distribution at steady state was significantly greater in patients with cirrhosis than in control patients (202 (82) litre vs 121 (49) litre). However, this difference did not change terminal elimination half-life. The pharmacokinetics of propofol given by infusion to maintain general anaesthesia were not affected markedly by moderate cirrhosis.

Adult↗

[Uncomplicated attack of malaria in an area with high resistance to chloroquine. I. Evaluation of a short treatment with quinine].

The good results achieved in the treatment of malaria with a 7 and 5 days one of quinine (orally dose 8 mg/kg/8 h), incited the authors to try a 3 days long treatment at the same dose. They experimented this protocol on hospitalised children. All patients were free of parasites at day 7 with an average residual concentration quinine of 2.7 +/- 0.8 mg/l. Among the 7 patients with malaria at day 14, 4 didn't require another treatment and 2 presented new infestation. 50% of plasmodial isolated strains were chloroquine resistant and 40% amodiaquine resistant. The efficiency of this protocol could be in favour of its larger use.

Adolescent↗

[The risks of bronchoscopy in coronary patients].

In order to study the electrical changes that may occur during bronchoscopy in coronary patients we have carried out continuous electrocardiographic recordings during the course of endoscopy in 36 patients. We have been able to compare two groups: Group 1 consisting of 18 patients with coronary disease, and Group 2 with 18 non-coronary patients. There was no difference for sex, age or blood gases at the time of the examination in either group. Continuous electrocardiographic recording was started one hour before the examination and went on until two hours after, and was analysed as a function of the different durations of the endoscopy and any possible incidents. The blood potassium and the lidocaine blood levels at the end of the examination did not differ between the two groups. We observed no disorders of rhythm or of conduction. The only common change in the two groups was a frequent elevation of heart rate. There was no difference between the two groups. We have on the other hand been able to show in 3 coronary patients problems of repolarisation, which looked like current ischaemia occurring during the bronchoscopy and disappearing after the examination. We had no clinical upsets and do not have to regret having done any of the examinations, but these observations suggest we should be particularly careful in considering the indications for bronchoscopy, and the surveillance of patients during bronchoscopy where there is coronary disease.

Adult↗

Prevention of Pneumocystis carinii pneumonia relapse by pentamidine aerosol in zidovudine-treated AIDS patients.

To examine the efficacy and tolerance of pentamidine aerosol in the prevention of Pneumocystis carinii pneumonia (PCP) relapse in patients with the acquired immunodeficiency syndrome (AIDS) being treated with zidovudine, 51 patients who had had an episode of PCP in the previous 5 months were enrolled in a randomised controlled study. 25 patients (group I) received pentamidine mesylate aerosol (4 mg/kg every 2 weeks for the first month then monthly) and zidovudine, and 26 patients (group II) zidovudine alone. 3 group I patients withdrew from pentamidine therapy prematurely and were excluded from the analysis of efficacy. Relapses of PCP occurred in 2 out of 22 (9%) group I patients and in 16 out of 26 (61%) group II patients after a mean follow-up of 10 and 8.7 months, respectively. The two groups differed significantly (p less than 0.0001) in proportions without relapse. They did not differ in proportions surviving. Bronchial intolerance was common (47%); no systemic side-effects of pentamidine were observed. Pentamidine aerosol thus seems to be effective in preventing PCP relapses in AIDS patients on zidovudine. The early termination of the trial prevented assessment of the long-term efficacy and safety of pentamidine given by aerosol.

Acquired Immunodeficiency Syndrome↗

Serum bactericidal activity against Enterobacteriaceae producing broad-spectrum beta-lactamases in volunteers administered ofloxacin and cefotaxime, alone or combined.

The activity of ofloxacin and cefotaxime, alone or combined, against four strains of Enterobacteriaceae was evaluated both in vitro and in sera from volunteers given a single infusion over 30 min of 200 mg ofloxacin or 1 g cefotaxime. The strains showed resistance or decreased susceptibility to third-generation cephalosporins. The combination was not found to be synergistic in vitro. Analysis of the bactericidal titres and killing kinetics of sera taken at the time of the peak concentration and 6 h after the infusion, respectively, confirmed the absence of synergy between the drugs against these strains.

Cefotaxime↗

Capillary gas chromatography and tandem mass spectrometry of paf-acether and analogs: absence of 1-O-alkyl-2-propionyl-sn-glycero-3-phosphocholine in human polymorphonuclear neutrophils.

Fast atom bombardment-tandem mass spectrometry was used to identify molecular species of paf-acether (paf) produced by human polymorphonuclear neutrophils. Using this biological material, normal phase high performance liquid chromatography was necessary prior to the fast atom bombardment-tandem mass spectrometry step. Gas liquid chromatography/electron capture detection after hydrolysis with phospholipase C and conversion to heptafluorobutyrate derivatives was used to confirm the results. The results indicated the presence of mainly 1-O-hexadecyl/octadecyl-2-acetyl-sn-glycero-3-phosphocholine, acyl analogs of paf and only trace amounts of other alkyl analogs of paf. We did not detect the 2-propionyl analog of paf. Moreover, supplementation of human polymorphonuclear neutrophils with sodium propionate did not result in formation of the 2-propionyl analog of paf.

Electrons↗

Comparison of tissular disposition of pentamidine mesylate in the rat after aerosol or parenteral administration.

The tissular distribution of pentamidine mesylate (4 mg/kg as free base) after intravenous, intramuscular, and aerosol administration in healthy rats was examined. Pentamidine levels in the plasma, lungs, liver, kidneys, and other organs were determined by high-performance liquid chromatography. Pentamidine was undetectable in the plasma after day 5. At day 1, the injected groups had high concentrations of the drug in the kidneys (32-34 micrograms/g) and spleen with much lower concentrations in the lungs and the liver (3.12-5.70 micrograms/g and 1.64-2.19 micrograms/g, respectively). Aerosol delivery of pentamidine produced negligible extrapulmonary drug levels (3.29 micrograms/g in kidneys at day 1) and high sustained pulmonary levels throughout the 60 d of the study (range 5.42-19.62 micrograms/g). The half-time of elimination was longer in the lungs and kidneys (29-45 d) than in the liver (1.4-7.0 d) regardless of the mode of administration.

Aerosols↗

Reduction in biliary excretion of ceftriaxone by diclofenac in rabbits.

The effects of diclofenac, a nonsteroidal anti-inflammatory drug, on biliary excretion of ceftriaxone were evaluated in rabbits. In a previous study, we demonstrated that diclofenac increased the extravascular diffusion and antibacterial efficacy of ceftriaxone without any effect on serum protein binding and urinary excretion of this antibiotic. We perfected a surgical procedure that allowed the study of biliary secretion in conscious rabbits with a stable hemodynamic state. The kinetic study was carried out on the fourth day of treatment with ceftriaxone alone (30 mg/kg per day given intramuscularly; group 1) or combined with diclofenac (1.5 mg/kg per 12 h given intramuscularly; group 2). Cumulative biliary excretion of ceftriaxone over 6 h was significantly reduced in group 2 (5,291.6 +/- 2,017.5 micrograms in group 1 versus 1,379.1 +/- 567.1 micrograms in group 2). This phenomenon occurred without any change in biliary flow. Indocyanine green clearance (20 mg/kg) increased in animals treated with ceftriaxone alone compared with the saline-treated control group (55.04 +/- 4.68 versus 33.29 +/- 7.52 ml/min per kg, respectively). Diclofenac alone caused a significant decrease in indocyanine green clearance compared with clearance in controls (25.05 +/- 4.74 versus 33.29 +/- 7.52 ml/min per kg), and indocyanine green clearance appeared not significantly different from control values in animals receiving ceftriaxone plus diclofenac. These results suggest that (i) ceftriaxone could increase hepatic blood flow and (ii) reduction of the hepatic clearance of ceftriaxone by diclofenac may be due to hepatic hemodynamic variations involving diclofenac inhibition of prostaglandin synthesis, although an interaction of diclofenac with hepatic uptake of ceftriaxone cannot be ruled out.

Animals↗

Comparison of plasma concentrations of aerosolized pentamidine in nonventilated and ventilated patients with pneumocystosis.

Pentamidine concentrations were determined in plasma after a single aerosolization of 4 mg/kg pentamidine base on 18 patients breathing spontaneously (Group I) and in eight patients receiving mechanical ventilation (Group II). All the patients had documented pneumocystosis. Large interindividual variations in concentrations appeared, especially in Group I. Low concentrations were observed in Group I: Cmax = 65.6 +/- 9.4 micrograms/L (mean +/- SEM), contrasting with high levels in Group II: Cmax = 215.8 +/- 49.8 micrograms/L (mean +/- SEM). Consequently, the mean area under the curve from zero to 4 h was 2.6-fold higher in Group II than in Group I. These findings underline the risk of dose-related pentamidine toxicity in ventilated patients treated with aerosolized pentamidine and the interest of plasma pentamidine monitoring.

Acquired Immunodeficiency Syndrome↗

[Relation of the kinetics of the antisecretory effect and kinetics of blood concentration in man. Comparing cimetidine and ranitidine].

The time course of antisecretory effects of ranitidine and cimetidine and their relationship to plasma concentration were studied in 4 healthy volunteers. Placebo, cimetidine (266 mg) or ranitidine (100 mg) were infused during one hour preceding the 90 minute assessment of food-stimulated gastric acid secretion (intragastric titration); cimetidine and ranitidine blood levels and gastric acid outputs were measured at 15 min intervals. For each test a significant (p less than or equal to 0.01) correlation was found between concentration and effect. The half-life effect of ranitidine (t1/2 E) was significantly (p less than or equal to 0.05) greater than t1/2 E of cimetidine whereas their plasma half-lives (t1/2) were similar. The ratio t1/2 E/t1/2 was significantly (p less than or equal to 0.05) lower with cimetidine than with ranitidine. Explanations for this discrepancy are analyzed according to various hypotheses. The determination of t1/2 E seems to be a good approach to the duration of action of H2-antagonists. Our results show that the ratio t1/2 E/t1/2 and the t1/2 E might be important pharmacokinetic parameters to compare various H2-receptor antagonists.

Adult↗

Effects of propofol on baroreflex control of heart rate and on plasma noradrenaline levels.

The effects of propofol induction (2.5 mg kg-1) and of two continuous infusion rates of propofol (100 and 200 micrograms kg-1 min-1) on baroreflex control of heart rate and on plasma noradrenaline concentration were investigated in 11 unpremedicated patients. Baroreflex function was assessed using a pressor test (phenylephrine) and a depressor test (sodium nitroprusside). In addition, samples for subsequent determination of plasma noradrenaline levels and blood propofol levels were collected before each test. Baroreflex sensitivity and plasma noradrenaline concentrations were not significantly changed at any time of the study. By contrast, a significant and sustained resetting of baroreflex set point was observed, allowing unchanged heart rate at lower arterial pressure. It is concluded that the effects of propofol on baroreflex function and noradrenaline concentration are moderate.

Adult↗

[Diffusion of ofloxacin in infected ascitic fluid].

The ofloxacin diffusion was investigated in 13 cirrhotic patients with spontaneous bacterial peritonitis. Plasma and ascitic samples were collected at times H1, H31 and H8 after a first dose of 200 mg per os, in these 13 patients, after 4.5 or 6 days of 200 mg per os each 8 hours in 9 out of them. After the first dose, the plasmatic and ascitic concentrations, measured by High Performance Liquid Chromatography (HPLC), were between 0 and 3.62 mg/l, 0 and 1.95 mg/l respectively. The steady state concentrations are higher than the MIC'S for the organisms most commonly involved, comparable in the plasma and the ascitic fluid is good and suggest the interest of its use in this indication.

Adult↗