Background Intravenous racemic ketamine is commonly administered for procedural sedation, although few pharmacokinetic studies have been conducted among children. Moreover, an optimal sampling schedule has not been derived to enable the conduct of pharmacokinetic studies that minimally inconvenience study participants. Methods Concentration-time data were obtained from 57 children who received 1-1.5 mg·kg-1 of racemic ketamine as an intravenous bolus. A population pharmacokinetic analysis was conducted using nonlinear mixed effects models, and the results were used as inputs to develop a D-optimal sampling schedule. Results The pharmacokinetics of ketamine were described using a two-compartment model. The volume of distribution in the central and peripheral compartments were 20.5 l70 kg-1 and 220 l70 kg-1, respectively. The intercompartmental clearance and total body clearance were 87.3 and 87.9 l·h-170 kg-1, respectively. Population parameter variability ranged from 34% to 98%. Initially, blood samples were drawn on 3-6 occasions spanning a range of 14-152 min after dosing. Using these data, we determined that four optimal sampling windows occur at 1-5, 5.5-7.5, 10-20, and 90-180 min after dosing. Monte Carlo simulations indicated that these sampling windows produced precise and unbiased ketamine pharmacokinetic parameter estimates. Conclusion An optimal sampling schedule was developed that allowed assessment of the pharmacokinetic parameters of ketamine among children requiring short-term procedural sedation.
- optimal sampling strategy
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Anesthesiology and Pain Medicine