The bioavailability of bromazepam, omeprazole and paracetamol given by nasogastric feeding tube

Aims: To characterize and compare the pharmacokinetic profiles of bromazepam, omeprazole and paracetamol when administered by the oral and nasogastric routes to the same healthy cohort of volunteers. Methods: In a prospective, monocentric, randomized crossover study, eight healthy volunteers received the three drugs by the oral (OR) and nasogastric routes (NT). Sequential plasma samples were analyzed by high-performance liquid chromatography-UV, pharmacokinetic parameters (Cmax, $${\text{AUC}}_{0 - \infty }$$ , t½, ke, tmax) were compared statistically, and Cmax, $${\text{AUC}}_{0 - \infty }$$ and tmax were analyzed for bioequivalence. Results: A statistically significant difference was seen in the $${\text{AUC}}_{0 - \infty }$$ of bromazepam, with nasogastric administration decreasing availability by about 25%: AUCOR = 2501 ng mL−1 h; AUCNT = 1855ng mL−1 h (p  0.05); ratio (geometric mean) = 1.01 (90% CI 0.64-1.61). An extended study with a larger number of subjects may possibly provide clearer answers. The narrow 90% confidence limits of paracetamol indicate bioequivalence: AUCOR = 37μg mL−1 h; AUCNT = 41μg mL−1 h(p > 0.05); ratio (geometric mean) = 1.12 (90% CI 0.98-1.28). Conclusion: The results of this study show that the nasogastric route of administration does not appear to cause marked, clinically unsuitable alterations in the bioavailability of the tested drug

Formaldehyde-releasers: relationship to formaldehyde contact allergy. Contact allergy to formaldehyde and inventory of formaldehyde-releasers

This is one of series of review articles on formaldehyde and formaldehyde-releasers (others: formaldehyde in cosmetics, in clothes and in metalworking fluids and miscellaneous). Thirty-five chemicals were identified as being formaldehyde-releasers. Although a further seven are listed in the literature as formaldehyde-releasers, data are inadequate to consider them as such beyond doubt. Several (nomenclature) mistakes and outdated information are discussed. Formaldehyde and formaldehyde allergy are reviewed: applications, exposure scenarios, legislation, patch testing problems, frequency of sensitization, relevance of positive patch test reactions, clinical pattern of allergic contact dermatitis from formaldehyde, prognosis, threshold for elicitation of allergic contact dermatitis, analytical tests to determine formaldehyde in products and frequency of exposure to formaldehyde and releasers. The frequency of contact allergy to formaldehyde is consistently higher in the USA (8-9%) than in Europe (2-3%). Patch testing with formaldehyde is problematic; the currently used 1% solution may result in both false-positive and false-negative (up to 40%) reactions. Determining the relevance of patch test reactions is often challenging. What concentration of formaldehyde is safe for sensitive patients remains unknown. Levels of 200-300 p.p.m. free formaldehyde in cosmetic products have been shown to induce dermatitis from short-term use on normal skin

A comparative study of formaldehyde detection using chromotropic acid, acetylacetone and HPLC in cosmetics and household cleaning products

Chromotropic acid and acetylacetone methods for qualitative determination of formaldehyde were tested in parallel on 48 commercial samples, with high-performance liquid chromotography (HPLC) implemented for quantitative measure. In addition, interference with the detection of formaldehyde was investigated by analyzing 12 other aldehydes and ketones, 7 essential oils and 3 polysorbates. Throughout this comparative study, the disadvantages of the chromotropic acid method, of which 2 variants were used, were delineated and we found that the acetylacetone test proved to be a more efficient screening method for formaldehyde detection in a clinical laboratory

Développement d'une solution orale pédiatrique de captopril

Introduction: Le captopril, inhibiteur de l'enzyme de conversion de l'angiotensine, est largement utilisé dans le traitement de l'hypertension artérielle et de l'insuffisance cardiaque chez l'adulte et l'enfant . De par son instabilité en milieu aqueux (oxydation en captopril disulfure), il n'est actuellement commercialisé que sous forme de comprimés. La prescription fréquente de doses faibles et variables en pédiatrie justifiait le développement d'une forme orale liquide, tant sur le plan pratique et économique, que sur celui de la sécurité d'administration. Cependant toutes les formulations orales liquides publiées présentent une stabilité courte, ne dépassant guère 1 mois. Objectif: Développer une forme orale liquide de captopril d'une stabilité d'au moins 6 mois. Méthode: Sur la base des données de la littérature, élaboration de 8 formulations liquides différentes de captopril 1 mg/ml (concentration permettant le prélèvement d'un volume adéquat pour une administration en pédiatrie). Mise au point d'une « stability indicating method » par HPLC par des tests de dégradation accélérée à la chaleur (100°C), en milieu acide, basique, en présence d'un agent oxydant et de la lumière. Sélection de la formulation la plus stable durant le premier mois. Etude de stabilité sur 2 ans de 3 lots (3 échantillons/lot) dans leur conditionnement final à température ambiante (TA), au frigo et à 40° ± 2°C. Contrôle microbiologique au début et à la fin de l'étude selon la méthode de la Ph. Eur. (Ed. 3). Résultats: La formule retenue est une solution aqueuse de captopril 1 mg/ml additionnée d'EDTA 1 mg/ml comme stabilisateur et conditionnée dans des flacons VERAL en verre brun de 60 ml. Après dégradation dans les conditions définies ci-dessus, le pic du captopril est nettement séparé sur les chromatogrammes de ceux des produits de dégradation. Après 2 ans, la concentration mesurée est de 104.6% (±0.32%) au frigo, 103.6% (±0.86%) à TA et 96.5 % (±0.02%) à 40°C. Aucune croissance n'a été observée sur la durée de l'étude. Discussion et conclusion: La solution de captopril 1 mg/ml mise au point est simple à préparer. En partant du principe actif pur et en présence d'EDTA comme complexant, les traces de métaux éventuellement présents n'induisent pas l'oxydation du captopril et par conséquent le recours à d'autres stabilisateurs n'est pas nécessaire. La méthode HPLC développée est une « stability indicating method ». Les résultats de l'étude ont montré que cette solution a une durée de validité de 2 ans au frigo et à TA. Compte tenu du fait que la préparation ne contient pas d'agent antimicrobien, une conservation au frigo (2 - 8°C) est toutefois recommandée. La formule proposée présente un réel avantage en pédiatrie tant sur le plan de la sécurité d'administration que sur celui de l'économie

Intestinal absorption in patients after cardiac surgery.

OBJECTIVES: We designed this study to assess intestinal absorption in patients with adequate or altered hemodynamic status after cardiac surgery and to test clinical tolerance to early enteral nutrition. DESIGN: Prospective, descriptive study. SETTING: Surgical intensive unit in a university teaching hospital. PATIENTS: Cardiac surgery patients, age 64+/-10 yrs (mean +/-SD) were subdivided into two groups according to hemodynamic status: group I, 16 patients with adequate hemodynamic status; group II, 23 patients with hemodynamic failure. These groups were compared with healthy controls (group III, n = 6). INTERVENTIONS: Paracetamol pharmacokinetic study on days 1 and 3 with nasogastric or postpyloric paracetamol administration. Early postpyloric or conventional gastric nutrition in group II. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations were measured on days 1 and 3, and area under the curve (AUC) was calculated. Absorption was strongly reduced on day 1 in all patients after gastric administration (lower peak paracetamol and AUC), but normal after postpyloric delivery. Duration of anesthesia and of circulatory bypass did not affect paracetamol absorption. On day 3, AUC was close to normal in case of hemodynamic failure. Peak absorption on day 1 was negatively correlated with opiate dose (r2 = 0.176, p = .008). Hypocaloric enteral nutrition was well tolerated. CONCLUSIONS: The close-to-normal AUC, during low cardiac output, despite lower peak paracetamol, shows absorption was not suppressed, only delayed, because of decreased pyloric motility. The decrease on day 1 can be attributed to opiates, known to alter pyloric function and to slow down the intestinal transit

Quality and safety of parenteral nutrition for newborn and preterm infants as an on-ward preparation.

For newborn and preterm infants, standardised and individual parenteral nutrition (PN) is used. PN preparation is at risk for contamination and dosing errors. The quality of PN is crucial for infants and has a direct impact on their health status and safety. The aim of this study is to evaluate the physicochemical and microbial quality of PN for newborn and preterm infants prepared on a neonatal ward. Sampling of various individual PN prepared by nurses on a neonatal ward was performed. Formulations included maximal four electrolytes, variable dextrose and amino acid concentrations. Depending on the sample volume, up to three quality analyses were performed: (1) test for bacterial endotoxins by kinetic-chromogenic method, (2) sterility according to the European and US Pharmacopoeia, and (3) quantification of electrolytes by capillary electrophoresis and of dextrose by ultraviolet detection after enzymatic reaction of hexokinase. The concentrations obtained were evaluated based on the US and Swiss Pharmacopoeia specifications for compounded preparations and compared to the widened pharmacy specifications. The composition of 86% of the 110 analysed PN prepared by nurses on the neonatal ward corresponded to their medical prescription. 14% were out of the acceptable widened pharmacy ranges. We found no microbial contamination in the samples. All PN were free from endotoxins. Component concentrations of PN prepared on wards by nurses differed frequently and significantly from their medical prescription, and the deviation can be critical depending on the component and its mode of action. The sample size is too small to evaluate the microbial contamination

Formulation optimization in a university hospital - The example of pediatric solutions of the ACE inhibitor captopril.

Many major drugs are not available in pediatric form. As a result, hospital pharmacists are often requested to provide the medical staff with liquid formulations for individualized dosage and easy administration to newborn and young patients. Such in-house formulations must of course fulfil stringent criteria of purity and stability. This paper reports the development of a liquid solution of captopril for pediatric use. A specific HPLC-UV method was developed. A number of formulations described in the literature as affording one-month stability were examined and found wanting. A simple solution of the drug (1 mg/ml) in purified water containing 0.1% EDTA-Na proved chemically and microbiologically stable at room temperature for two years