Pharmacokinetics and metabolism of rectally administered paracetamol in preterm neonates
a Department of Paediatrics, Division of
Neonatology, Sophia Hospital PO Box 10400 8000 GK Zwolle, The Netherlands, b Department of Hospital Pharmacy, c Department of Paediatrics, Arkansas Children's Hospital and
University of Arkansas for Medical Sciences, Little Rock, AR, USA, d Department of Paediatric Surgery,
Sophia Children's Hospital, Rotterdam, The
Netherlands, e Department of Paediatrics,
Wilhelmina Children's Hospital, Utrecht, The Netherlands
Correspondence to: Dr R A van Lingen.
Accepted 7 August 1998
AIM
To investigate the pharmacokinetics,
metabolism, and dose-response relation of a single rectal dose of
paracetamol in preterm infants in two different age
groups.
METHODSPreterm infants
stratified by gestational age groups 28-32 weeks (group 1) and 32-36
weeks (group 2) undergoing painful procedures were included in this study. Pain was assessed using a modified facies pain
score.
RESULTSTwenty one infants in group 1 and
seven in group 2 were given a single rectal dose of 20 mg/kg body
weight. Therapeutic concentrations were reached in 16/21 and 1/7
infants in groups 1 and 2, respectively. Peak serum concentrations were
significantly higher in group 1. Median time to reach peak
concentrations was similar in the two groups. As serum concentration
was still in the therapeutic range for some infants in group 1, elimination half life (T1/2) could not be determined
in all infants: T1/2 was 11.0 ± 5.7 in 11 infants
in group 1 and 4.8 ± 1.2 hours in group 2. Urinary excretion was
mainly as paracetamol sulphate. The glucuronide:sulphate ratio was 0.12 ± 0.09 (group 1) and 0.28 ± 0.35 (group 2). The pain score did not
correlate with therapeutic concentrations.
CONCLUSIONSA 20 mg/kg single dose of paracetamol
can be safely given to preterm infants in whom sulphation is the major
pathway of excretion. Multiple doses in 28-32 week old neonates would
require an interval of more than 8 hours to prevent progressively
increasing serum concentrations.
© 1999 by Archives of Disease in Childhood
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