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BackgroundExposure to deficient or excess glucocorticoids is associated with increased morbidity in patients with adrenal insufficiency. An age-appropriate low dose hydrocortisone formulation is not available and manipulation of adult medication is required with potential for inaccurate dosing. Licensed pharmaceutical products must contain ±10% of labelled drug content.AimsTo assess the variability in manipulation procedures undertaken by parents/carers and to quantify the dose-variability in the manipulated product based on the method of preparation.MethodsParents of children with adrenal insufficiency completed a survey assessing the methods used to manipulate hydrocortisone 10 mg tablets. A sub-group were asked to manipulate a scored 10 mg hydrocortisone tablet (Auden Mackenzie brand) to provide the prescribed dose for their child as they would at home. Hydrocortisone content was analysed according to the current European Pharmacopoeial method.ResultsOne hundred and twenty-nine parents completed the questionnaire. Overall 55% of parents break or cut the tablet and 43% suspend the tablet in water prior to administration. 34% are prescribed a dose indivisible by 2.5 mg of whom 33% break the tablet to acquire the dose. Twenty-seven parents/carers participated in the sub-study and the target doses they prepared ranged from 0.5–7.5 mg. Forty eight percent of the preparations were within 10% of the target dose; 74% were within 20% and 82% were within 30%. Based on this small sample size the most accurate method of tablet manipulation is to split the tablet along the score lines. However, this is only possible for doses divisible by 2.5 mg. Dispersion of the tablet in water and withdrawal of the relevant volume was associated with poor accuracy.ConclusionsChildren are at risk of suboptimal dosing when parents/carers are required to manipulate adult products to provide the appropriate dose to children. This risk is greatest when doses need to be prepared via dispersion of a tablet and calculation of the volume to withdraw. This may be related to the poor solubility of hydrocortisone which makes formation of a homogenous liquid difficult. There is a need for age-appropriate hydrocortisone products to be available to children.AcknowledgementThis study was funded via an unrestricted research grant from Diurnal Ltd.

Early prediction of response to growth-promotion treatments in children is needed so that ineffective treatment may be discontinued at an early stage. We have evaluated a number of biochemical markers for their ability to predict growth response in 33 short, healthy, prepubertal children. Treatments (for which ethical approval was given) were as follows: placebo growth hormone (4 children), growth hormone alone (18), oxindralone alone (4), growth hormone and oxandralone combined (7). We measured total alkaline phosphatase (ALP), bone ALP (by leetin affinity electrophoresis), procollagen type I propeptide (PICP) and procollagen type III propeptide (PIIIP, both by radioimmunoassay) at entry to the study, and after 3 months of treatment. Height velocity was recorded at entry to the study and after one year. In the placebo group, there was little change in any of the markers after 3 months, nor in height velocity after one year (p >0.1, paired t-test). In each of the other treatment groups, significant increases in all four markers occurred at 3 months, and in height velocity at one year (p <(0.05, paired t-test). For all treatment groups combined, the increment in each biochemical marker at 3 months was significantly correlated (p <0.01) with the increment in height velocity found after one year, the best overall predictor of response was bone ALP (r= 0.70). Within the group treated with growth hormone alone, PIIIP was the best predictor of growth response (r= 0.52, p <0.05); pretreatment height velocity was of little value (r=-0.29, p >0.05). We conclude that biochemical markers of growth can successfully predict response to growth promoting treatments in children.