Y Furet

The pharmacokinetic parameters of paracetamol were studied after 15 min intravenous infusion of 15 mg/kg of propacetamol (Prodafalgan) in 5 neonates aged less than 10 days and 7 infants aged between 1 and 12 months. Blood was sampled at 0, 0.5, 2 and 6 h after the first intravenous infusion of propacetamol. The infants aged less than 10 days had higher plasma concentrations of paracetamol, a longer half-life (3.5 vs. 2.1 h) and a lower plasma clearance (0.149 vs. 0.365 l/h/kg) than the older children. Dose simulations were performed on the basis of individual data of each child in order to obtain steady-state plasma concentrations between 4 and 18 mg/l permitting the best antipyretic effect for each child. In infants aged less than 10 days a 15 mg/kg dose of propacetamol four times a day (i.e. 30 mg/kg/day paracetamol) is sufficient, corresponding to the dosage recommended by the French pharmacopoeia. On the other hand, double the dosage, nearer to the American dosage, is necessary for children aged over 10 days.

The aim of the present study was to characterize amphotericin B aerosols nebulized by ultrasonic and jet nebulizers and to study their deposition and pharmacokinetics in patients with pulmonary mycetoma. The aerodynamic behaviour and pulmonary deposition of amphotericin B particles were measured using a direct isotopic method based on stable labelling of the drug with 99mTc. Each nebulizer was bench tested for inhaled mass and particle size distribution. Three patients suffering from pulmonary aspergilloma were enrolled for a 4 week clinical study. They received 5 mg of amphotericin B daily delivered by either Fisoneb or DP100 (ultrasonic) or Respirgard II (jet) nebulizers. Deposition of radiolabelled amphotericin B was measured once with each nebulizer using a gamma-camera. In two patients, amphotericin B serum concentration was monitored over a 330 min period after the nebulization had been completed. Inhaled masses of the three nebulizers, assessed as % of labelled drug caught in inspiratory filter in duplicate experiments, were: 5.8 and 3.6% for Respirgard II; 26.5 and 28.3% with Fisoneb; 5.9 and 6.3% for DP100. Mass median aerodynamic diameter (mean +/- SD) results were: 0.28 +/- 0.04 micron with Respirgard II; 4.82 +/- 0.78 microns with Fisoneb; and 2.27 +/- 1.14 microns with DP100. Because of larger particles and significantly greater inhaled mass, Fisoneb delivered more amphotericin B to the central airways, the lung periphery and in the mycetoma lung regions. Amphotericin B serum concentrations correlated with pulmonary deposition and remained below 25 ng.mL-1. No untoward effects were reported by the patients during the 4 week trial.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of this study was to assess a residual gravimetric method based on weighing dry filters to measure the aerosol output of nebulizers. This residual gravimetric method was compared to assay methods based on spectrophotometric measurement of terbutaline (Bricanyl, Astra Zeneca, France), high-performance liquid chromatography (HPLC) measurement of tobramycin (Tobi, Chiron, U.S.A.), and electrochemical measurements of NaF (as defined by the European standard). Two breath-enhanced jet nebulizers, one standard jet nebulizer, and one ultrasonic nebulizer were tested. Output produced by the residual gravimetric method was calculated by weighing the filters both before and after aerosol collection and by filter drying corrected by the proportion of drug contained in total solute mass. Output produced by the electrochemical, spectrophotometric, and HPLC methods was determined after assaying the drug extraction filter. The results demonstrated a strong correlation between the residual gravimetric method (x axis) and assay methods (y axis) in terms of drug mass output (y = 1.00 x -0.02, r(2) = 0.99, n = 27). We conclude that a residual gravimetric method based on dry filters, when validated for a particular agent, is an accurate way of measuring aerosol output.

Colistin aerosols are frequently administered to patients with cystic fibrosis. However, questions arise concerning the effect of both jet and ultrasonic nebulizers on the properties of the drug. The aim of this study was to characterize the anti-Pseudomonas aeruginosa (PA) activity of colistin after jet (Pari LL) and ultrasonic (DP100) nebulization. A bench study was performed by capturing the aerosols, determining the drug mass, and assessing its anti-PA activity. Because the inhaled mass of colistin had to be entirely recovered for the bacteriological study, it was assessed by isotopic methods, mixing the drug with a 99mTc-labelled tracer and demonstrating that 99mTc activity accurately predicted the mass of colistin. Colistin was extracted from the filters and its antibiotic activity was determined using the method employed for the study of the bacteriostatic and bactericidal power of serum on the ATCC 27853 PA strain. The postnebulization minimum inhibitory concentrations (MIC) were 1.9 micrograms.mL-1 with DP100 and 0.5 microgram.mL-1 with Pari LL. These values were less than two dilutions different from the 1 microgram.mL-1 MIC of non-nebulized colistin. We conclude that neither jet nebulization nor ultrasonic nebulization alter the antibiotic properties of colistin and that both systems can be used to nebulize colistin.

Les critères d'acceptabilité définis en 1991 par les “ Centers for Disease Control ” ou CDC, pour le dosage du plomb sanguin sont de +/- 40 μg/L pour les valeurs inférieures à 400 μg/L et de 10 % pour les valeurs supérieures. Actuellement, avec un seuil de décision de déclaration obligatoire du saturnisme de 100 μg/L et l'évolution des techniques d'analyse, les critères précédemment annoncés pour les valeurs inférieures à 400 μg/L ne semblent plus acceptables. Le groupe de travail "Toxiques Industriels" de la SFTA propose d'actualiser ces données en réalisant une étude multicentrique sur la variabilité du dosage de la plombémie pour des concentrations faibles proches de 100 μg/L. Cette étude a été réalisée dans 12 laboratoires sur quatre pools de sang prélevé sur EDTA. Ces pools ont été préparés de façon à obtenir une valeur de plombémie dans les quatre fourchettes suivantes : <30 ; 31 à 70 ; 71 à 100 et 101 à 150 μg/L. Les échantillons ont été analysés par les laboratoires sur cinq jours différents par spectrométrie d'absorption atomique électrothermique (SAAE) ou par spectrométrie d'émission en plasma induit couplée à la spectrométrie de masse (ICP-MS). Les plombémies ont été mesurées par SAAE (n=12) et/ou ICP-MS (n = 4). Tous les échantillons étaient préparés par le même laboratoire. Chaque participant de l'étude a reçu anonymement 40 échantillons (5 séries incluant 8 échantillons de chaque niveau de concentration). Pour chacune des concentrations, les moyennes obtenues par les deux techniques ne diffèrent pas significativement mais les coefficients de variations sont en général deux fois plus élevés en SAAE. Pour les quatre niveaux de concentration (niveau 1 à 4), les moyennes des plombémies mesurées par l'ensemble des méthodes sont respectivement de 30,3 μg/L, 47,5 μg/L, 82,8 μg/L et 129,4 μg/L pour des CV de 14,8%, 12,1%, 9,1 % et 7,5 %. Les moyennes des CV intra laboratoires pour les quatre niveaux sont respectivement de 7,6 %, 6,5 %, 5,2 % et 4,9 %. Cette étude permet d'actualiser les données de la littérature sur les performances du dosage de la plombémie par deux techniques couramment utilisées dans les laboratoires : la SAAE et l'ICP-MS. Pour des valeurs proches du seuil de décision de la déclaration obligatoire du saturnisme, les valeurs de dispersion des mesures sont plus faibles que celles qui servent encore aujourd'hui de référence en pratique clinique.