Pharmacokinetics of a single bolus of propofol in Chinese children of different ages
Matthews, Ivan (1), Smith, Fang Gao (2), Aarons, Leon (1)
(1) School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, UK. (2) Department of Anaesthesia and Intensive Care Medicine, Birmingham Heartlands Hospital, UK.
Objectives: 1. To determine a complete pharmacokinetic profile of a single dose of propofol in different aged Chinese children ranging from 4 months to 9 years old. 2. Provide further evidence to support the use of propofol for induction in children younger than 3 years old. 3. Build and use pharmacokinetic models that can accurately describe propofol concentrations in the target population. 4. Establish the population pharmacokinetic parameters and investigate covariate models for prediction of typical parameters in an individual before concentration measurements are available.
Methods: Arterial blood samples were obtained from thirty-five Chinese children at 2, 4, 6, 8, 10, 20, 30, 45, 60, 90, 120, 180 mins after a single IV bolus of propofol (3 mg.kg-1). The plasma concentrations of propofol were measured using high-performance liquid chromatography with an ultraviolet detector. Population parameter values were estimated using NONMEM. One, two and three compartment pharmacokinetic models were fitted to the data using subroutines from the NONMEM library.
Results: A three-compartment pharmacokinetic model best described the pharmacokinetics of propofol. Clearance was 0.185 L.min-1, volume of distribution of the central compartment was 7.41 L, the peripheral volumes of distribution were 54.6 L and 7.2 L while the inter-compartmental clearances were 0.614 L.min-1 and 0.692 L.min-1 for a child of the average weight of 13.7kg. The half-lives were 2.67 min, 14.89 min and 310.60 min. Covariate models were applied and weight was found to be a significant covariate for the clearance and volume of distribution parameters. No significant age effect could be demonstrated on clearance or volume of distribution parameters after weight had been taken into account.
Conclusions: The study was successful in determining a pharmacokinetic profile of propofol in Chinese children. It supports the case that the pharmacokinetic properties of propofol do not differ substantially across Chinese children aged between 4 months and 9 years after weight has been accounted for and thus supports the use of propofol for induction in those under 3 years of age. A three compartment population pharmacokinetic model with weight as a covariate on clearance and volume parameters was found to successfully describe and predict propofol concentrations in the target population.