Effects of maturation and size on population pharmacokinetics of pentoxifylline and its metabolites in very preterm infants with suspected late-onset sepsis or necrotizing enterocolitis: a pilot study incorporating clinical outcomes.
Administration, Intravenous
Body Weight
/ physiology
Drug Therapy, Combination
/ methods
Enterocolitis, Necrotizing
/ blood
Female
Humans
Infant
Infant, Extremely Premature
/ blood
Infant, Newborn
Infant, Premature, Diseases
/ blood
Infant, Very Low Birth Weight
/ blood
Male
Metabolic Clearance Rate
/ physiology
Models, Biological
Pentoxifylline
/ administration & dosage
Phosphodiesterase Inhibitors
/ administration & dosage
Pilot Projects
Sepsis
/ blood
Time Factors
Treatment Outcome
late-onset sepsis
lisofylline
necrotizing enterocolitis
pentoxifylline
population pharmacokinetics
preterm infant
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
03
04
2018
revised:
08
08
2018
accepted:
09
09
2018
pubmed:
4
10
2018
medline:
31
12
2019
entrez:
4
10
2018
Statut:
ppublish
Résumé
Infection-induced inflammation is associated with adverse long-term outcomes in preterm infants. Pentoxifylline (PTX) is a candidate for adjunct immunomodulatory therapy in preterm infants with late-onset sepsis (LOS) and necrotizing enterocolitis (NEC), but pharmacokinetic data in this population are extremely limited. This study aims to characterize the pharmacokinetic properties of intravenous PTX and its metabolites in preterm infants. An open label pilot clinical study of intravenous PTX as an adjunct therapy in preterm infants (gestation <32 weeks) with suspected LOS or NEC was undertaken. PTX was infused for 12 h for two days (60 mg kg The preterm infants (n = 26) had a median (range) gestation of 24.8 weeks (23.3-30.4) and birthweight of 689 g (370-1285). PTX was well tolerated and without treatment-limiting adverse effects. Changes in size (weight) and maturation were successfully modelled for PTX and metabolites. After allometric scaling, clearance increased with postmenstrual age, increasing by approximately 30% per week for PTX and M1 (lisofylline) and simulations of current dosing demonstrated a six-fold difference in exposure between 24 and 35 weeks postmenstrual age. The developed model can be used to explore dosing strategies based on size and maturation for preterm infants.
Identifiants
pubmed: 30281170
doi: 10.1111/bcp.13775
pmc: PMC6303212
doi:
Substances chimiques
Phosphodiesterase Inhibitors
0
Pentoxifylline
SD6QCT3TSU
Types de publication
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
147-159Informations de copyright
© 2018 The British Pharmacological Society.
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