The aims were to critically assess methodologies relevant to PK studies tailored to the needs of children. In view of the significant challenges associated with pain control in children paracetamol and ketorolac were selected for the study. Methods: Two bioanalytical methods were developed to measure paracetamol and enantiomers of ketorolac in paediatric samples, to support PK studies of IV paracetamol and ketorolac in children less than 16 years old. All studies had ethical approval and clinical trial authorisation. Results: The developed bioanalytical methods were reliable, requiring only 30 μl of blood for paracetamol, and 50 μl of plasma for ketorolac. Paracetamol concentrations from finger-prick samples in the first hour post dose were greater than from venous samples (349% at 15, 72% at 30, and 9.3% at 60minutes). There were no differences in median CL (0.41, 0.31 and 0.37 1h<sup>-1</sup>kg<sup>-1</sup>), V<sub>d</sub> (0.90, 0.95 and 0.90 1/kg) and t<sub>1/2</sub> (1.7, 2.2 and 1.6 h) among the respective age groups 2-5, 6-10 and 11-15 years. All PK parameters were different for R- and S- ketorolac, with V<sub>d</sub> and CL of R- being lower than those of S- (0.12 vs. 0.17 1/kg; 0.017 vs. 0.049 1/h/kg). The median half-life of R- was longer than that of S- (5.0 vs. 3.1 h, <i>P =</i> 0.043). Conclusions: Bioanalytical method did not limit PK trials in children. Sampling method affected PK parameter estimation, and prolonging cannula patency was the most challenging procedure during blood sampling. The PK of IV paracetamol was similar in children 2-15 years old, and the enantiomers of ketorolac were found to have different PKs in children.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:540342 |
| Date | January 2010 |
| Creators | Mohammed, Baba Suleman |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=165857 |
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