Pharmacokinetics of Intravenous Melatonin in Preschool-Aged Pediatric Surgical Patients

BACKGROUND: Melatonin may have several beneficial clinical effects in the perioperative setting. In children, it has been studied for preoperative anxiety, postoperative pain, and emergence delirium. Melatonin's pharmacokinetic profile is well-known in adults, but data in young children are sparse. We aimed to investigate the pharmacokinetic parameters of an intravenous intraoperative bolus of melatonin in pediatric surgical patients.

METHODS: We enrolled 20 participants aged 1-6 years undergoing general anesthesia for elective surgery to receive an intravenous melatonin dose of 0.15 mg·kg-1 before end of surgery. A total of six blood samples were drawn from each participant at the following time points: baseline, 0, 15, 30, 60, and 90 min post-injection. Plasma melatonin concentrations were determined with High-Performance Liquid Chromatography with Fluorescence Detection (HPLC-FLD). Pharmacokinetic parameters were estimated with non-compartmental analysis. Clinical outcomes were recorded.

RESULTS: We included 98 samples in the pharmacokinetic analysis. We found a maximum plasma concentration (Cmax) of 416 298 [IQR 322 230-508 006] pg·mL-1 and an elimination half-life (t1/2) of 35.2 (SD 8.4) minutes. Clearance (CL) was 0.0183 (SD 0.0039) L·min-1·kg-1 and volume of distribution (Vd) 0.92 (SD 0.27) L·kg-1. There were no cases of emergence delirium, mean maximum pain (FLACC) score was 1.3 (SD 2.0), and time to awakening and discharge readiness averaged one and two hours, respectively. Adverse events could be attributed to routine postoperative symptoms.

CONCLUSION: Administering intravenous melatonin in a dose of 0.15 mg·kg-1 in 1-6-year-olds yielded pharmacokinetic characteristics comparable to those reported in adults. The observed postoperative events were consistent with expected perioperative findings. These data support dose selection for trials investigating the perioperative use of melatonin in children.

TRIAL REGISTRATION: CTIS: EU CT 2024-517592-20.

CLINICALTRIALS: gov: NCT05541276 (registered 12/09-2022).