Multistep Unified Models Using Prior Knowledge for the Prediction of Drug Clearance in Neonates and Infants

Journal of Clinical Pharmacology
Million A TegengeRichard Forshee

Abstract

Allometric approaches are widely used for interspecies scaling for the prediction of pharmacokinetic (PK) parameters during drug development. The concept of allometry can also be extended to predict PK parameters from adults to children. Three methods for extrapolating pediatric clearance were developed and evaluated using the clearance values of 4 drugs. The first method was established using a simple allometric (SA) model with estimated coefficient and exponent based on data ranging from children older than 2 years to adult. Then we developed a unified multistep single-exponent (MSE) and multistep body-weight-dependent exponent (MBDE) models. The major steps in these 2 new methods include generating pseudopredicted clearance for unobserved new populations such as preterm neonates, term neonates, and infants. Subsequent steps involve incorporating the pseudopredicted clearance with the actual PK data from older children and adults. All 3 models were then used to predict drug clearance in children ≤2 years old (N = 278). Drug clearance was predicted with mean absolute error of 29.6, 14.2, and 12.9 using SA, MSE, MBDE, respectively. The root mean square error was 65.9, 29.8, 24.7 for SA, MSE, MBDE, respectively. Approximately 41...Continue Reading

References

Jun 1, 1959·A.M.A. Journal of Diseases of Children·J M SUTHERLAND
May 4, 2006·British Journal of Clinical Pharmacology·Iftekhar Mahmood
Aug 30, 2008·British Journal of Anaesthesia·K J S AnandUNKNOWN NEOPAIN Trial Investigators Group
Aug 14, 2010·Paediatric Anaesthesia·Brian J Anderson, Peter Larsson
Jan 31, 2012·Pharmaceutical Research·Chenguang WangCatherijne A J Knibbe
Oct 12, 2013·Drug Metabolism and Drug Interactions·Carl-Michael Staschen, Iftekhar Mahmood
Nov 13, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jeannine S McCuneNicholas H G Holford
Apr 12, 2014·Anesthesia and Analgesia·Douglas J EleveldMichel M R F Struys
May 9, 2014·European Journal of Clinical Pharmacology·Christian DiestelhorstGeorg Hempel
May 27, 2015·Journal of Clinical Pharmacology·Tanay S SamantStephan Schmidt
Aug 12, 2016·Clinical Pharmacokinetics·Elisa A M CalvierCatherijne A J Knibbe

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Citations

May 30, 2020·The Journal of International Medical Research·Yan YueDezhi Mu
Mar 29, 2021·Advanced Drug Delivery Reviews·John P GleesonKathryn A Whitehead
Jun 30, 2021·Journal of Clinical Pharmacology·Jian WangGilbert J Burckart

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