The enantioselective population pharmacokinetics of intravenous ketorolac in children using a stereoselective assay suitable for microanalysis.

OBJECTIVE: To describe the effect of age and body size on enantiomer selective pharmacokinetic (PK) of intravenous ketorolac in children using a microanalytical assay. METHODS: Blood samples were obtained at 0, 15 and 30 min and at 1, 2, 4, 6, 8 and 12 h after a weight-dependent dose of ketorolac. Enantiomer concentration was measured using a liquid chromatography tandem mass spectrometry method. Non-linear mixed-effect modelling was used to assess PK parameters. KEY FINDINGS: Data from 11 children (1.7-15.6 years, weight 10.7-67.4 kg) were best described by a two-compartment model for R(+), S(-) and racemic ketorolac. Only weight (WT) significantly improved the goodness of fit. The final population models were CL = 1.5 × (WT/46)(0.75) , V1 = 8.2 × (WT/46), Q = 3.4 × (WT/46)(0.75) , V2 = 7.9 × (WT/46), CL = 2.98 × (WT/46), V1 = 13.2 × (WT/46), Q = 2.8 × (WT/46)(0.75) , V2 = 51.5 × (WT/46), and CL = 1.1 × (WT/46)(0.75) , V1 = 4.9 × (WT/46), Q = 1.7 × (WT/46)(0.75) and V2 = 6.3 × (WT/46)for R(+), S(-) and racemic ketorolac. CONCLUSIONS: Only body weight influenced the PK parameters for R(+) and S(-) ketorolac. Using allometric size scaling significantly affected the clearances (CL, Q) and volumes of distribution (V1 , V2 ).

Can finger-prick sampling replace venous sampling to determine the pharmacokinetic profile of oral paracetamol?

UNLABELLED: WHAT IS ALREADY KNOWN ABOUT THE SUBJECT: Finger-prick blood samples are increasingly used for the clinical and biomedical measurement of drugs and endogenous substance concentration. The use of different sampling sites can give rise to different drug concentration measurements. WHAT THIS STUDY ADDS: During the absorption phase, the paracetamol concentration in finger-prick blood samples is significantly greater than that in venous blood samples, following oral administration. Finger-prick and venous blood samples will result in equivalent pharmacokinetic parameters of oral paracetamol only after distribution equilibrium is attained. The drive to increase the availability of paediatric pharmacokinetic data with minimum blood loss has led to the development of micro-sampling techniques. However studies have suggested that pharmacokinetic data from venous or capillary blood samples may not be directly comparable. AIM: The aim of this study was to determine whether paracetamol demonstrates concentration differences between finger-prick and venous blood samples. METHODS: Paired finger-prick and venous blood samples were taken at 0, 15, 30 and 60 min following 1 g oral paracetamol, from 12 male adult subjects. Paracetamol concentration was determined using HPLC and UV detection with a LLOQ of 2200 pg on column. Intra-assay coefficient of variation for paracetamol at the LLOQ was 3%. RESULTS: At 15, 30, and 60 min post dose the median finger-prick paracetamol concentration was 349%, 72%, and 9.3% greater than the equivalent venous concentrations, respectively. Regression analysis confirmed a significant relationship between finger-prick and venous paracetamol concentrations at 15 min (r(2) = 0.81, P = 0.006), at 30 min (r(2) = 0.82, P < 0.0001) and at 60 min (r(2) = 0.87, P < 0.0001) post dose. The regression equation for venous and finger-prick blood concentrations at 15, 30 and 60 min post dose were Venous(15) = Finger(15) - 3.4, Venous(30) = Finger(30) - 3.4 and Venous(60) = 0.68 Finger(60) + 3.06, respectively. CONCLUSIONS: Paracetamol demonstrates an arteriovenous difference in concentration, and the use of finger-prick samples may give rise to results which differ from those obtained with traditional venous sampling especially during the first 1 h following drug ingestion.