Gilbert Koch (1), Johannes Schropp (2), Marc Pfister (1)
(1) Paediatric Pharmacology and Pharmacometrics Research Centre, University of Basel, Children’s Hospital (UKBB), Basel, Switzerland (2) Department of Mathematics and Statistics, University of Konstanz, Konstanz, Germany
Objectives: Accidental once or repeated overdosing is a frequent and potentially fatal clinical situation affecting paediatric and adult patients [1],[2]. A critical question after a period of overdosing is to understand the time it will take for the drug concentration to return to the target range associated with correct reference dose. We developed a method that calculates the optimal waiting time between a period of overdosing and the next reference dose to ensure safe and efficacious treatment.
Methods: A general mathematical framework was developed to calculate the waiting time after overdosing until the next correct therapeutic dose can be administered. We related the drug concentration after last overdose to the target range characterized by the steady state concentration with the reference dosing. The resulting equation is then solved to compute the waiting time.
Results: For simplicity our method was applied to a one-compartment model and intravenous drug administration. The mathematical solution permits to calculate the waiting time between the last overdosing and the next therapeutic dose based on half-life of a given drug. The approach calculates the waiting time independently of the volume of distribution, a major advantage as this parameter is usually not known in clinical practice. Two real-life overdosing scenarios are presented. First, we investigate a tenfold amikacin overdose in a one day old preterm neonate. Second, we analyse multiple overdosing of vancomycin over an entire week in an infant with undiagnosed impairment of kidney function. An online available Time to Next Dose (TND) calculator was developed to support clinicians who care for optimized treatment adjustment after overdosing.
Conclusions: This is the first quantitative approach to assess the waiting time after accidental overdosing to ensure safe and efficacious continuation of necessary treatment. The presented work is another step to bridge the gap between pharmacometric modelling and application of precision medicine in clinical practice. The developed online TND decision support tool helps clinicians to efficiently adjust treatment after accidental overdosing benefiting paediatric and adult patients.
References:
[1] Ghaleb MA et al. (2010) The incidence and nature of prescribing and medication administration errors in paediatric inpatients, Arch Dis Child 95:113-18
[2] Lewis PJ et al. (2009) Prevalence, incidence and nature of prescribing errors in hospital inpatients, Drug Safety 32(5):379-89
Reference: PAGE 25 (2016) Abstr 5780 [www.page-meeting.org/?abstract=5780]
Poster: Drug/Disease modeling - Safety