Population Pharmacokinetics of Alfentanil in Children.

Abstract

Alfentanil is an opioid analgesic and anesthetic agent used in surgical procedures. Despite its widespread use in children, the U.S. Food and Drug Administration label lacks specific dosing recommendations for those under 12 years. A population pharmacokinetic analysis was performed using NONMEM (v7.5) to characterize alfentanil's disposition in children. The study included 58 plasma concentrations from 42 patients who received intravenous alfentanil as part of usual care. Median age was 7.57 years (range: 0.33-17.80) and median dosing was 12.5 mcg/kg (range: 4-43). A one-compartment model with first-order elimination best described alfentanil's pharmacokinetics. Among body size measures, total body weight (WT) significantly influenced clearance (CL [L/h]) = 7.42 × (WT/70)^0.75) and volume of distribution (V [L]) = 12.6 × (WT/70)1). Inter-individual variability decreased after the inclusion of WT, coefficients of variation were reduced from 104% to 58% and from 169% to 83%, for CL and V, respectively. The final model facilitated simulations to achieve target efficacious analgesic and anesthetic concentrations. For analgesia, an initial 10 mcg/kg bolus (for the first hour) followed by an 8 mcg/kg/h infusion (starting at 1 h) achieved the efficacious targeted concentrations (10-100 ng/mL). For procedures that typically require minimal or moderate sedation, a 25 mcg/kg bolus followed by a 20 mcg/kg/h infusion (starting at 5 min) achieved the targeted concentrations (50-200 ng/mL, depending on the procedure). These regimens should be prospectively evaluated to ensure their safety and confirm their efficacy. Overall, this study provides valuable insights into pharmacokinetics and dosing of alfentanil in children.