The cidofovir plasma levels were below those leading to toxicity. The levels and the AUC were dose dependent in children but not in adults. Diffusion from the injected site was greatest in a few adults and unpredictable. Because of the great individual variation in diffusion in adults, cidofovir should be used at less than the recommended intravenous dose to prevent any risk of systemic toxicity.

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.

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Objectives Melatonin is commonly prescribed in paediatric population, but it is commercially only available in tablet form. Oral suspensions are useful pharmaceutical preparations faced with difficulties from the pharmaceutical industry to provide medicines to children. Ready-for-use suspending agents are used, although their compositions are unsuitable for children. A new liquid vehicle for oral suspensions, Inorpha, was commercialised with a formulation adapted in paediatrics. The stability of a melatonin oral suspension 2 mg/mL in Inorpha was studied. The physicochemical and microbiological stabilities were respectively evaluated during 6  and 4 months. Methods A validated high-performance liquid chromatography method was used to assess the melatonin concentration under room temperature and refrigerated conditions weekly. A validated microbiological method was employed on 10 mL vials, on the one hand, and one 200 mL bottle opened every day, on the other hand, in order to evaluate respectively the microbiological stability before opening and under conditions of use. Results After 18 weeks under room temperature and refrigerated conditions, samples held respectively a melatonin minimal concentration of 99.3% and 96.7% of initial concentration. After 6 months, melatonin concentration was 96.1% of initial concentration. Total aerobic microbial counts obtained during the 4-month microbiological study were <10 CFU/mL. None of the melatonin suspensions presented fungal growth. Conclusions Variation of the active ingredient concentration did not exceed 5% after 6 months. Microbial enumeration assays demonstrated microbiological stability of suspensions over a period of 4 months. The microbiological quality was not altered by repeated openings of the bottle allowing production of multidose vials.

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