The design of a pharmacokinetic study of Intranasal Fentanyl

Objective:  To create a sampling schedule for a population pharmacokinetic study of Intranasal Fentanyl (INF) in paediatric patients presenting to the emergency department of a tertiary care hospital.

Methods:   A search of the literature was conducted to determine reasonable assumptions regarding the underlying structural model, pharmacokinetic parameters and appropriate methods for scaling down values of adult parameters to corresponding paediatric values if required. In addition to this potential models for maturation of fentanyl clearance were explored
Optimised sampling times were generated via Winpopt by entering various competing models for selected ages (3 months, 1,3,7 and 16 years).  Competing models varied in number of samples, upper limit for final collection, allometric exponent used to scale the absorption rate constant as well as maturation model chosen.  Sampling windows were generated and compared across competing models. 

Results:   We could find no literature regarding the pharmacokinetics of INF in the paediatric population.  A previously published maturation model (1) for propofol was chosen to represent the likely scencario of fentanyl maturation is similar to propofol as both are CYP3A4 probes.  To scale the adult value of the absorption rate constant allometric exponents of ¼, ¾ and 1 were tested for final effect on sampling schedule.  Diversity was seen in the optimised sampling schedules for competing models with some overlap of optimised sampling windows. Using five samples adequately accurate parameter estimates were achieved for the majority of competing models.   Two sampling strategies were chosen based on age group (3 months-3 years, 7-16 years).

Conclusion:   A sampling protocol has been created for the study of INF in paediatric patients; this strategy takes into account the need to precision of parameter estimation along with the practical constraints of studies involving paediatric patients.

1. Sumpter A, Anderson BJ. Pediatric pharmacology in the first year of life. Curr Opin Anaesthesiol 2009;22(4):469-75.