Continuous infusion of methylprednisolone via paediatric parenteral nutrition: a pharmacokinetic animal study.

BACKGROUND & AIMS: The aim of our study consisted to measure the pharmacokinetic parameters of methylprednisolone administered in a continuous infusion of a paediatric parenteral nutrition mixture for 24h in the rabbit. METHODS: Fourteen rabbits were split into two groups and assigned a different administration vehicle (all-in-one or two-in-one nutrition mixture). We used USC PACK* pharmacokinetics software to compare the influence of the composition of the paediatric parenteral nutritional solutions on the values of the pharmacokinetic parameters of methylprednisolone. RESULTS: Neither the steady-state plasma concentrations of methylprednisolone hemisuccinate nor the values of the pharmacokinetic parameters of methylprednisolone differed significantly when administered in two-in-one or all-in-one nutrition mixtures. CONCLUSIONS: The composition of the nutritional medium had no discernable effect on the bioavailability of methylprednisolone. Neither the speed at which the steady-state plasma concentration was reached, nor the values of the pharmacokinetic parameters of methylprednisolone were significantly modified.

Leaching of diethylhexyl phthalate from multilayer tubing into etoposide infusion solutions.

PURPOSE: The extent of leaching of diethylhexyl phthalate (DEHP) from various polyvinyl chloride (PVC), polyethylene (PE), coextruded (PVC and PE), and triple-layered (PVC, ethyl vinyl acetate, and PE) i.v. extension tubing into etoposide infusion solutions was studied. METHODS: Different lengths of tubing (25, 50, and 80 cm) were tested in two types of experiments: (1) static, in which the etoposide solution was left in contact inside the tubing for various times and then removed, and chromatography was used to quantify the DEHP content of the effluate, and (2) dynamic, in which infusion was simulated using syringe reservoirs, and three flow rates were tested to assess the effect of flow rate on the quantities of DEHP leached. RESULTS: The static study showed that large quantities of DEHP were leached from all tubing types except the PE tubing. The dynamic study confirmed that leaching occurred, although the values were below the threshold limit of 5 microg/mL. The values varied depending on flow rate, tubing length, and etoposide concentration. The coextruded and triple-layered i.v. tubing did not provide the inertness and safety they are intended to have, as DEHP not only leached out but did so in quantities almost equivalent to those found with tubing made of PVC only. CONCLUSION: DEHP leached rapidly from PVC, coextruded, and triple-layered i.v. tubing into etoposide infusion solution. The quantity of DEHP found in the infusion solution was influenced by the length of the tubing and concentration of etoposide.

Methylprednisolone sodium succinate in pediatric parenteral nutrition: influence of vehicle injection.

Many drugs can be administered in parenteral nutrient mixtures, but no work on the delivery of corticoids by such means is reported. We studied the influence of pediatric parenteral nutrient mixtures on the kinetic parameters of the corticoid methylprednisolone injected in an intravenous bolus in rabbits as its sodium succinate ester. Four groups of six male New Zealand rabbits were used. After extraction, the plasma drug concentrations were measured by high performance liquid chromatography. The distribution volume of the ester and the clearance rates of the two entities (ester and methylprednisolone) were lowered in the presence of a lipid emulsion. The description of these pharmacokinetic parameters provides a basis for a preclinical study of 24h administration of methylprednisolone in a parenteral nutrient mixture.

Analysis by liquid chromatography and infrared spectrometry of di(2-ethylhexyl)phthalate released by multilayer infusion tubing.

Di(2-ethylhexyl)phthalate (DEHP), a plasticiser present in infusion equipment, is known to be harmful to human health. Various studies have shown that DEHP is released into drug solutions from polyvinyl chloride (PVC) infusion lines. New multi-layer tubing has therefore been marketed to overcome this problem. We assessed the inertness of this tubing when placed in contact with a solution of CELLTOP. Chromatographic assay of DEHP showed no significant difference in DEHP levels in the solution when placed in contact with PVC and with multi-layer tubing. Analysis by infrared spectrometry showed that DEHP was initially present in the polyethylene layer of the multi-layer tubing even before contact with the drug solution. Contact with the solution results in release of DEHP from the container into the contents. The substance responsible for this release is in fact an excipient of CELLTOP, polysorbate. This release of DEHP further proves to depend on parameters such as temperature, time of contact between solution and tubing, and the concentration of polysorbate in the infused drug solution.

Influence of unclogging agents on the surface state of enteral feeding tubes.

BACKGROUND: Despite standardized prevention procedures, recalcitrant clogging of enteral feeding tubes is observed, which requires recourse to varied unclogging agents. Some of these agents have proved effective in routine use, but their impact on the surface state of the tube materials has never been studied. In this work, the authors tested the impact of different unclogging agents on the materials used for these tubes (polyurethane and silicone). METHODS: Enteral feeding tubes were placed in contact with different agents in vitro, and the surface state of the material was analyzed using 2 different methods: infrared spectroscopy and scanning electron microscopy. To assess the surface state of the silicone and polyurethane tubes, negative controls (undamaged tubes) and positive controls (deliberately damaged tubes) were used for each type. RESULTS: The infrared spectroscopy method did not reveal any damage to the surface of either the silicone or the polyurethane tubes with either treatment. The test results by scanning electron microscopy showed that orange juice, pineapple juice, and cola had no detrimental action on the tube biomaterials under current conditions of clinical practice. CONCLUSIONS: Although some studies have advocated using polyurethane tubes to administer medication, silicone appears to be less vulnerable to damage by the agents tested.

Simple assay of plasma sevoflurane and its metabolite hexafluoroisopropanol by headspace GC-MS.

The anesthetic sevoflurane can now be delivered over periods of up to 48h using a newly developed medical system, the AnaConDa (anesthetic conserving device). Lack of pharmacokinetic data on sevoflurane and its main metabolite (hexafluoroisopropanol, HFIP) in this indication prompted us to develop a headspace GC-MS method to quantify the two substances. The only previously published method for assaying the two substances could not be adapted to our study since it uses expensive and rarely employed system components together with toxic carbon disulfide as a dilution solvent. The method developed is straightforward and uses the relatively non-toxic solvent undecane as dilution solvent and chloroform as internal standard. The method is linear for a concentration range of 1-150microg/ml, and presents high accuracy and precision. LOD and LOQ are 0.2 and 1microg/ml, with a short analysis time (7.6 min for a single analysis). The method was applied to determine the plasma levels of sevoflurane and HFIP in six patients under 48-h anesthetic sedation delivered via the AnaConDa system. Average sevoflurane and HFIP concentrations plateaued at 75 and 4microg/ml, respectively. Sevoflurane quickly tailed off after inhalation was stopped, and HFIP levels remained low.

Sevoflurane protects rat mixed cerebrocortical neuronal-glial cell cultures against transient oxygen-glucose deprivation: involvement of glutamate uptake and reactive oxygen species.

BACKGROUND: The purpose of this study was to clarify the role of glutamate and reactive oxygen species in sevoflurane-mediated neuroprotection on an in vitro model of ischemia-reoxygenation. METHODS: Mature mixed cerebrocortical neuronal-glial cell cultures, treated or not with increasing concentrations of sevoflurane, were exposed to 90 min combined oxygen-glucose deprivation (OGD) in an anaerobic chamber followed by reoxygenation. Cell death was quantified by lactate dehydrogenase release into the media and cell viability by reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium by mitochondrial succinate dehydrogenase. Extracellular concentrations of glutamate and glutamate uptake were assessed at the end of the ischemic injury by high-performance liquid chromatography and incorporation of L-[H]glutamate into cells, respectively. Free radical generation in cells was assessed 6 h after OGD during the reoxygenation period using 2',7'-dichlorofluorescin diacetate, which reacts with intracellular radicals to be converted to its fluorescent product, 2',7'-dichlorofluorescin, in cell cytosol. RESULTS: Twenty-four hours after OGD, sevoflurane, in a concentration-dependent manner, significantly reduced lactate dehydrogenase release and increased cell viability. At the end of OGD, sevoflurane was able to reduce the OGD-induced decrease in glutamate uptake. This effect was impaired in the presence of threo-3-methyl glutamate, a specific inhibitor of the glial transporter GLT1. Sevoflurane counteracted the increase in extracellular level of glutamate during OGD and the generation of reactive oxygen species during reoxygenation. CONCLUSION: Sevoflurane had a neuroprotective effect in this in vitro model of ischemia-reoxygenation. This beneficial effect may be explained, at least in part, by sevoflurane-induced antiexcitotoxic properties during OGD, probably depending on GLT1, and by sevoflurane-induced decrease of reactive oxygen species generation during reoxygenation.