¹Departments of Pediatrics and Hospital Pharmacy, Isala Clinics/Sophia Hospital, Zwolle; the Department of Pediatrics, Wilhelmina Children's Hospital, Utrecht; and the Department of Pediatric Surgery, Sophia Children's Hospital, Rotterdam, The Netherlands

Correspondence: Richard A. van Lingen, MD, Department of Pediatrics, Isala Clinics/Sophia Hospital, PO Box 10400, 8000 GK Zwolle, The Netherlands. E-mail:vanlingen@wxs.nl

^*Dr Quak was supported in part by a grant from the Sophia Hospital Affiliation Fund.

Presented in part at the Fourth International Symposium on Pediatric Pain, Helsinki, Finland, July 2-4, 1997.

Received 5 May 1999; Accepted 17 August 1999.

Abstract

Objective: To investigate pharmacokinetics and pharmacodynamics of rectally administered acetaminophen (INN, paracetamol) in term neonates directly after birth.

Methods: In this prospective clinical trial, term neonates wtih painful conditions or who were undergoing painful procedures received multiple-dose acetaminophen. Serum concentrations were determined serially with an HPLC method, and pharmacokinetic analysis was performed. Pain assessment was performed by means of a validated pain score.

Results: Ten consecutive term neonates received four rectal doses of acetaminophen, 20 mg/kg body weight, every 6 hours. Mean peak serum concentrations (SD) during multiple-dose administration were 10.79 6.39 mg/L, 15.34 5.21 mg/L, and 6.24 3.64 mg/L for the entire group, boys, and girls, respectively. There was a significant difference between the boys and the girls (P = .01). No serum concentrations associated with toxicity (>120 mg/L) were found. Median time to peak serum concentration was 1.5 hours after the first dose and 15 hours for multiple doses. Mean (SD) half-life was 2.7 1.4 hours in eight patients. There was no correlation between dose and serum concentration or between pain score and serum concentration. There was a significant inverse relationship between the preceding pain score and peak serum concentrations.

Conclusions: In term neonates, multiple rectal doses of acetaminophen, 20 mg/kg body weight, led to widely varying serum concentrations but did not result in therapeutic concentrations in all infants. Boys had higher peak concentrations. Because accumulation was not found, a dose of 30 mg/kg followed by doses of 20 mg/kg at 6- to 8-hour administration intervals are appropriate to reach therapeutic concentrations. A concentration–effect relationship could not be determined.