Pharmacokinetics and metabolism of rectally administered paracetamol in preterm neonates: Presented in part at the annual meeting of the European Society for Pediatric Research, Rotterdam, The Netherlands, July 3–6 1994.
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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. Methods—Preterm 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. Results—Twenty 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 (T ½) could not be determined in all infants: T ½ 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. CONCLUSIONS: A 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.
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In premature neonates, one study found mean elimination half-life of rectally administered paracetamol was 11 hours for 28-32 week neonates and 4-5 hours for 32-36 week neonates.
“In premature neonates, the mean elimination half-life is longer still; one study found it was 11 h for 28-32 week old neonates (for rectally administered paracetamol) and 4-5 h in 32-36 week old neonates.7”
From Paracetamol: pharmacology, prescribing and controversies (2016) · cites this paper as [7]
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- Authors
- van Lingen, R. A., Deinum, J. T., Quak, J. M. E., Kuizenga, A. J., van Dam, J. G., Anand, K. J. S., Tibboel, D., & Okken, A.
- Affiliations
- Arkansas Children's Hospital (US)
- Venue
- Archives of Disease in Childhood - Fetal and Neonatal Edition
- Publisher
- BMJ
- Published
- 1999-01-01
- Volume
- 80
- Issue
- 1
- Pages
- F59-F63
- ISSN
- 1359-2998 (ISSN-L)
- 1468-2052
- PMC
- PMC1720876
- OpenAlex
- W2038191147
- Cited by
- 147
- References
- 33
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 5 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 2 · 2017: 6 · 2016: 6 · 2015: 7 · 2014: 13 · 2013: 6 · 2012: 4
- FWCI
- 7.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Archives of Disease in Childhood Fetal & Neonatal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pediatric Pain Management Techniques
- Health Sciences › Medicine › Surgery › Anesthesia and Pain Management
- Keywords
- paracetamol, rectal administration, preterm infants, pharmacokinetics, drug metabolism, sulfation, glucuronidation, elimination half-life, dose-response relationship, neonatal pain, analgesia, gestational age
- MeSH terms
- Acetaminophen, Administration, Rectal, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Gestational Age, Half-Life, Humans, Infant, Newborn, Infant, Premature, Male, Pain Measurement, Regression Analysis, Time Factors, Statistics, Nonparametric, Analgesics, Non-Narcotic
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