Limited Sampling Strategies Supporting Individualized Dose Adjustment of Intravenous Busulfan in Children and Young Adults.

Background: Therapeutic drug monitoring (TDM) for busulfan supports dose adjustment during conditioning for stem cell transplantation. The authors aimed to develop and validate limited sampling strategies (LSS) of 4-5 samples for a precise estimation of the area under concentration (AUC)-time curve of busulfan, in plasma as an alternative to an intensive sampling strategy (ISS) requiring 9-10 samples.

Methods: ISS TDM data from 297 patients (≤18 years of age) were used.

Risk assessment in extrapolation of pharmacokinetics from preclinical data to humans.

Background: Prediction of pharmacokinetics in humans is essential for translating preclinical data to humans and planning safe and efficient clinical studies. The performance of various methods in extrapolation of preclinical pharmacokinetic data to humans is usually benchmarked by the fraction of predictions falling within a predefined interval that is centred on the value observed clinically. Recently, such an approach was used to compare physiologically based pharmacokinetic (PBPK) modelling and allometry in predicting the pharmacokinetics of a set of compounds in humans.

Extrapolating from animal studies to the efficacy in humans of a pretreatment combination against organophosphate poisoning.

The extrapolation from animal data to therapeutic effects in humans, a basic pharmacological issue, is especially critical in studies aimed to estimate the protective efficacy of drugs against nerve agent poisoning. Such efficacy can only be predicted by extrapolation of data from animal studies to humans. In pretreatment therapy against nerve agents, careful dose determination is even more crucial than in antidotal therapy, since excessive doses may lead to adverse effects or performance decrements.

Characterization of early plasma concentrations of midazolam in pigs after administration by an autoinjector.

The treatment of organophosphate-induced poisoning is based mainly on atropine and an oxime. Prompt anticonvulsive intervention is usually also required to terminate the ensuing seizure activity and to prevent delayed permanent brain damage. Midazolam, a water-soluble benzodiazepine agonist, has the advantage of rapid absorption following intramuscular administration.