medwireNews: Researchers have calculated the optimal times to take blood samples for measuring insulin-like growth factor (IGF)-1 levels in children with growth hormone deficiency (GHD) receiving the long-acting growth hormone MOD-4023.
Peak IGF-1 is best determined on day 2 after MOD-4023 dosing, but mean IGF-1 is better determined on day 4, report Dennis Fisher (P Less Than, San Francisco, California, USA) and co-workers in Hormone Research in Paediatrics.
The researchers observe that the development of long-acting GH “adds complexity” to the practice of adjusting GH levels to maintain IGF-1 values below +2 standard deviation score (SDS).
They therefore took four blood samples over a 1-year period from 52 patients, aged between 3 and 11 years, who were receiving treatment for GHD. Eleven children received standard daily recombinant human GH (rhGH) 0.034 mg/kg and 41 were taking weekly MOD-4023 at doses equivalent to 0.18, 0.35 and 0.48 mg/kg.
The researchers had previously developed pharmacokinetic and pharmacodynamic models in adults, based on much more frequent blood sampling, and they found that these were also a good fit for the sparser data they obtained from the paediatric patients, after accounting for weight in the pharmacokinetic models and change in IGF-1 with age in the pharmacodynamic model. This allowed them to predict MOD-4023, rhGH and IGF-1 levels at any given timepoint.
Peak IGF-1 SDS was best predicted by samples taken on day 2 after MOD-4023 dosing, with levels in samples taken on other days underestimating the true peak level. Mean IGF-1, on the other hand, was best reflected by levels in samples taken on day 4. Levels measured on days 2 and 3 overestimated the true mean, whereas those measured on days 6 and 7 underestimated it.
Although these days were optimal, the researchers note that “children will be available for clinic visits and blood sampling at different time points in the dosing interval.”
They say: “Thus, it is important to understand the relationship between values measured at different time points during the dosing interval and each of the mean and peak values.”
The “strong linear relationships” between time and IGF-1 SDS show that the models used in this study can “support dose selection and dose modification in future clinical studies”, they conclude.
By Eleanor McDermid
Horm Res Paediatr 2017; Advance online publication
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