Merck
  • Home
  • Search Results
  • Observational infant exploratory [(14)C]-paracetamol pharmacokinetic microdose/therapeutic dose study with accelerator mass spectrometry bioanalysis.

Observational infant exploratory [(14)C]-paracetamol pharmacokinetic microdose/therapeutic dose study with accelerator mass spectrometry bioanalysis.

British journal of clinical pharmacology (2015-01-27)
Colin R Garner, Kevin B Park, Neil S French, Caroline Earnshaw, Alessandro Schipani, Andrew M Selby, Lindsay Byrne, Sarah Siner, Francis P Crawley, Wouter H J Vaes, Esther van Duijn, Rianne deLigt, Heili Varendi, Jane Lass, Grzegorz Grynkiewicz, Wioletta Maruszak, Mark A Turner
ABSTRACT

The aims of the study were to compare [(14)C]-paracetamol ([(14)C]-PARA) paediatric pharmacokinetics (PK) after administration mixed in a therapeutic dose or an isolated microdose and to develop further and validate accelerator mass spectrometry (AMS) bioanalysis in the 0-2 year old age group. [(14)C]-PARA concentrations in 10-15 µl plasma samples were measured after enteral or i.v. administration of a single [(14)C]-PARA microdose or mixed in with therapeutic dose in infants receiving PARA as part of their therapeutic regimen. Thirty-four infants were included in the PARA PK analysis for this study: oral microdose (n = 4), i.v. microdose (n = 6), oral therapeutic (n = 6) and i.v. therapeutic (n = 18). The respective mean clearance (CL) values (SDs in parentheses) for these dosed groups were 1.46 (1.00) l h(-1), 1.76 (1.07) l h(-1), 2.93 (2.08) l h(-1) and 2.72 (3.10) l h(-1), t(1/2) values 2.65 h, 2.55 h, 8.36 h and 7.16 h and dose normalized AUC(0-t) (mg l(-1) h) values were 0.90 (0.43), 0.84 (0.57), 0.7 (0.79) and 0.54 (0.26). All necessary ethical, scientific, clinical and regulatory procedures were put in place to conduct PK studies using enteral and systemic microdosing in two European centres. The pharmacokinetics of a therapeutic dose (mg kg(-1)) and a microdose (ng kg(-1)) in babies between 35 to 127 weeks post-menstrual age. [(14)C]-PARA pharmacokinetic parameters were within a two-fold range after a therapeutic dose or a microdose. Exploratory studies using doses significantly less than therapeutic doses may offer ethical and safety advantages with increased bionalytical sensitivity in selected exploratory paediatric pharmacokinetic studies.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Ethyl alcohol, Pure, 190 proof, ACS spectrophotometric grade, 95.0%
Sigma-Aldrich
D-(+)-Glucose solution, 45% in H2O, sterile-filtered, BioXtra, suitable for cell culture
Sigma-Aldrich
D-(+)-Glucose solution, 100 g/L in H2O, sterile-filtered, BioXtra, suitable for cell culture
Sigma-Aldrich
α-D-Glucose, anhydrous, 96%
Sigma-Aldrich
Glucose solution, BioUltra, for molecular biology, ~20% in H2O