Pyry Välitalo1, Merja Kokki2,3, Veli-Pekka Ranta4, Klaus T Olkkola5, Andrew C Hooker6, Hannu Kokki7,8. 1. Division of Pharmacology, Leiden University, Leiden, The Netherlands. 2. Department of Anesthesia and Operative Services, Kuopio University Hospital, PO Box 100, FI-70029, Kuopio, Finland. 3. School of Medicine, University of Eastern Finland, Kuopio, Finland. 4. School of Pharmacy, University of Eastern Finland, Kuopio, Finland. 5. Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 6. Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden. 7. Department of Anesthesia and Operative Services, Kuopio University Hospital, PO Box 100, FI-70029, Kuopio, Finland. hannu.kokki@uef.fi. 8. School of Medicine, University of Eastern Finland, Kuopio, Finland. hannu.kokki@uef.fi.
Abstract
PURPOSE: The aim of the current population pharmacokinetic study was to quantify oxycodone pharmacokinetics in children ranging from preterm neonates to children up to 7 years of age. METHODS: Data on intravenous or intramuscular oxycodone administration were obtained from three previously published studies (n = 119). The median [range] postmenstrual age of the subjects was 299 days [170 days-7.8 years]. A population pharmacokinetic model was built using 781 measurements of oxycodone plasma concentration. The model was used to simulate repeated intravenous oxycodone administration in four representative infants covering the age range from an extremely preterm neonate to 1-year old infant. RESULTS: The rapid maturation of oxycodone clearance was best described with combined allometric scaling and maturation function. Central and peripheral volumes of distribution were nonlinearly related to bodyweight. The simulations on repeated intravenous administration in virtual patients indicated that oxycodone plasma concentration can be kept between 10 and 50 ng/ml with a high probability when the maintenance dose is calculated using the typical clearance and the dose interval is 4 h. CONCLUSIONS: Oxycodone clearance matures rapidly after birth, and between-subject variability is pronounced in neonates. The pharmacokinetic model developed may be used to evaluate different multiple dosing regimens, but the safety of repeated doses should be ensured.
PURPOSE: The aim of the current population pharmacokinetic study was to quantify oxycodone pharmacokinetics in children ranging from preterm neonates to children up to 7 years of age. METHODS: Data on intravenous or intramuscular oxycodone administration were obtained from three previously published studies (n = 119). The median [range] postmenstrual age of the subjects was 299 days [170 days-7.8 years]. A population pharmacokinetic model was built using 781 measurements of oxycodone plasma concentration. The model was used to simulate repeated intravenous oxycodone administration in four representative infants covering the age range from an extremely preterm neonate to 1-year old infant. RESULTS: The rapid maturation of oxycodone clearance was best described with combined allometric scaling and maturation function. Central and peripheral volumes of distribution were nonlinearly related to bodyweight. The simulations on repeated intravenous administration in virtual patients indicated that oxycodone plasma concentration can be kept between 10 and 50 ng/ml with a high probability when the maintenance dose is calculated using the typical clearance and the dose interval is 4 h. CONCLUSIONS:Oxycodone clearance matures rapidly after birth, and between-subject variability is pronounced in neonates. The pharmacokinetic model developed may be used to evaluate different multiple dosing regimens, but the safety of repeated doses should be ensured.
Authors: L Lindell-Osuagwu; M Hakkarainen; K Sepponen; K Vainio; T Naaranlahti; H Kokki Journal: J Clin Pharm Ther Date: 2013-12-16 Impact factor: 2.512
Authors: Chenguang Wang; Senthilkumar Sadhavisvam; Elke H J Krekels; Albert Dahan; Dick Tibboel; Meindert Danhof; Alexander A Vinks; Catherijne A J Knibbe Journal: Clin Drug Investig Date: 2013-07 Impact factor: 2.859