Off-label drug use among hospitalized children: identifying extent and nature
Objective of the study was to determine the extent and nature of medicinal products used off-label in hospitalized children and to highlight the therapeutic areas with the highest need. Over a 4 week period, data about prescribed drugs to patients under 18 years of age at two paediatric wards in Bratislava (Unit for Infants and Unit for Older Children) were recorded and the drug-licensing status according to valid Summary of Product Characteristics (SPC) was identified. In total, 206 medicinal products containing 70 different generic substances were given to 49 paediatric patients at the Unit for Infants. Of these, 22% were evaluated as off-label. The highest rates were established among the drugs used for diseases of respiratory system and diseases of digestive system. The 68 children had been given at the Unit for Older Children 267 medicinal products resulting in 97 generic substances. In 15.7% of cases medicines were used in off-label manner, mainly due to unapproved paediatric indication and age. This pilot study provided a preliminary survey on drugs administered off-label to paediatric patients in Slovak Republic.
Better medicines for children: challenges and unmet needs
This review deals with the use of medicinal products in children. Many medicinal products administered routinely to paediatric patients have been either not licensed for use in children (unlicensed use) or have been prescribed outside the terms of their product license (off-label prescribing). A lot of surveys have been conducted in the context of identifying the extent of off-label used drugs in children documenting high rates (45-60 %) of such use. Recognising and meeting challenges as development of suitable formulations for very young children and realization of clinical trials involving children present important steps in the enhancement of the present situation. To improve the health of children in Europe, the Regulation (EC) No 1901/2006 addressing the pharmaceutical industry, research teams and member states proposing important incentives and obligations was assigned. Paediatric Investigation Plan and Paediatric Use Marketing Authorisation present the key measures of the EU regulation on medicinal products for paediatric patients.
The efficacy of newly synthesised agent and natural antioxidant treatment in diabetic and hypertensive rats
Hypertension that develops as the result of cardiovascular damage in diabetes is one of the serious complications of diabetes. The aim of this study was to evaluate the changes in levels of oxidative stress and in endothelial NO synthase (eNOS) and heat shock protein 90 (Hsp90) expressions after the treatment of diabetic rats with a newly synthesised heteroarylaminoethanolic derivative 4/1E with potentially beta-adrenergic blockade effects and a strong antioxidant Pycnogenol®. The treatment of 6-weeks duration was indicated in the group of diabetic Wistar rats (DL; streptozotocin (STZ) 3×25 mg/kg i.p.) and hypertensive rats (HL, STZ) with 4/1E in the dose 10 mg/kg i.p. or with Pycnogenol® (DP, HP) in the dose 20 mg/kg p.o. Animals in control groups (C, H, D) received vehiculum. The levels of oxidative stress were assessed in kidney andliver as the activity of N-acetyl-β-D-glucosaminidase (NAGA) and the levels of thiobarbituric acid reactive substances (TBARs). The expression of eNOS and Hsp90 was assessed from the hearts of all animals using SDS-Page and Western blotting.
In our study the effects of newly synthesised drug 4/1E and Pycnogenol® on the levels of oxidative stress were comparable only in diabetic animals. The expression of eNOS was decreased in diabetic, but not hypertensive animals. The treatment with 4/1E did not affect the expression of eNOS unlike the treatment with Pycnogenol® after which the expression was significantly increased. The expression of Hsp90 was increased in both hypertensive and diabetic animals. The treatment with 4/1E was more effective in decreasing Hsp90 expression in both groups of animals than the treatment with Pycnogenol®.
The present study evaluates antihyperglycemic activity of fractionated Pycnogenol® and its ability to improve endothelial dysfunction
in diabetic animals. The aim of this study was to isolate from Pycnogenol® mixture its active compounds and compare
their efficacy on observed parameters. Pycnogenol® mixture was fractioned by re-extracting with petroleum ether, chloroform,
ethyl acetate and butanol, subsequently. Pycnogenol® mixture and fractions (butanolic, water, ethyl acetate) were administered
during 6 weeks to diabetic rats. Blood glucose levels were assessed from the arterio-venous blood at the beginning of experiment
and at the end of experiment. Endothelial dysfunction was evaluated as the contractile responses to phenylephrine and
acetylcholine. The amount of collagen I and III was assessed from thoracic aorta after picrosirius red staining. For the confirmation
of the changes on molecular level, we determinated endothelial NO synthase (eNOS) and heat shock protein 90 (Hsp90)
expression from left ventricle.
Overall, the result suggest, that fractions are not so effective on observed parameters as Pycnogenol® mixture itself, indicating
synergistic effect of the plant constituents.