A new intravenous formulation containing paracetamol is now available and widely used in children, but with limited paediatric pharmacokinetic data. This study was aimed at determining the effects of age on the pharmacokinetics (PK) of this formulation of paracetamol in children. Blood samples were obtained from 24 children at 0, 15, 30 minutes, then 1, 2, 4, 6 and 8 hours after the administration of 15 mg kg -1 of IV paracetamol. Paracetamol was quantified using an HPLC-UV method, with lower limit quantification of 2200 pg and an intra-assay coefficient of variation of 3%. In the paediatric age groups 2-5 years, 6 -10 years and 11-14 years, total clearance (CLt) in kg l -1 h -1 , was 0.41(0.20-0.57), 0.31(0.14-1.10) and 0.37(0.09-0.55) respectively; volume of distribution (Vd) in litres was 0.90(0.7-1.1), 0.95(0.7-1.6) and 0.90(0.4 -1.3) respectively; and elimination half-lives (t1/2) in hours was 1.7(1.1-2.6), 2.2(0.6-3.5) and 1.6(1.1-4.7), respectively. The PK parameters (CLt, Vd and t1/2) obtained did not differ significantly among the paediatric age groups (the p-value in all cases was greater than 0.05). In children 2-14 years, there were no significant relationships between the PK parameters and age, weight, height, body weight or body surface area.
Dried blood spots in Guthrie cards are a reliable means of blood sampling suitable for pharmacoki-netic analysis in children. The aim of this study was to develop a simple and reliable bioanalytical method to measure the concentration of paracetamol in dried blood spots. Paracetamol was ex-tracted from dry blood spots by precipitation using 30% perchloric acid and separated on Hichrom 3.5 μ C18column. Detection was by a Waters 486 Tunable Absorbance Detector, at a wavelength of 244 nm. From five adult volunteers blood samples were collected as dried blood spots before and at 15, 30, 60, 120, 240 and 420 minutes after 1 g oral paracetamol was administered. Cmax, Tmax, t1/2 and CL/F were calculated using non-compartmental analysis. The standard curve for the method was linear in the range 0 – 100 μg ml-1. The LLOD and LLOQ were 550 pg and 1100 pg, respectively, on column. The median (min., max) Cmax, Tmax, t1/2 and CL/F, were 14.6 μg ml-1 (9, 19.1), 45 minutes (15, 60), 2.3 hours (1.1, 2.7) and 0.31 L kg-1 (0.21, 0.36), respectively. We report a simple assay for the analysis of paracetamol that can be used for monitoring blood concentration of paracetamol in young children.Keywords: Bioanalytical, concentration, children, Guthrie, neonates
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