Document Detail


Population pharmacokinetics of intravenous caffeine in neonates with apnea of prematurity.
MedLine Citation:
PMID:  9209245     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The study the population pharmacokinetics of caffeine after intravenous administration to premature infants with apnea. METHODS: A prospective, blinded parallel study in which daily caffeine citrate doses of 30, 15, and 3 mg/kg were administered over 7 days by intermittent intravenous infusion. Arterial blood samples (three to six per patient) were assayed for caffeine content by means of HPLC. Population pharmacokinetic modeling was performed with NONMEM. RESULTS: Clearance (L/hr) = (0.00000399 . current weight [grams]) + (0.000128 . postnatal age [days]). For gestational age > 28 weeks, volume of distribution (L) = (0.000764 . weight [grams] + (0.0468 . postnatal age [days]); for gestational age < or = 28 weeks, volume of distribution (L) = (0.000755 . weight [grams]) + (0.0224. postnatal age [days]). Interpatient variability (coefficient of variation, in percent) was approximately 25% for clearance and approximately 11% for volume of distribution. Intrapatient error (standard deviation) was 3.9 mg/L. There was insignificant bias between observed and model-predicated serum caffeine concentrations in a separate group of 30 infants. CONCLUSIONS: Caffeine was well tolerated at all doses. Clearance was markedly lower and volume of distribution was higher than the values reported previously for term infants and adults. Both parameters were significantly influenced by postnatal age and current body weight, whereas volume of distribution in infants > 28 weeks' gestational age was higher than that in more premature babies. The predictive performance and the clinical application of the derived population models was satisfactorily shown.
Authors:
T C Lee; B Charles; P Steer; V Flenady; A Shearman
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Publication Detail:
Type:  Clinical Trial; Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical pharmacology and therapeutics     Volume:  61     ISSN:  0009-9236     ISO Abbreviation:  Clin. Pharmacol. Ther.     Publication Date:  1997 Jun 
Date Detail:
Created Date:  1997-07-15     Completed Date:  1997-07-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372741     Medline TA:  Clin Pharmacol Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  628-40     Citation Subset:  AIM; IM    
Affiliation:
School of Pharmacy, University of Queensland, St. Lucia, Australia.
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MeSH Terms
Descriptor/Qualifier:
Apnea / blood*
Caffeine / administration & dosage,  pharmacokinetics*
Chromatography, High Pressure Liquid
Female
Gestational Age
Humans
Infant, Newborn
Infant, Premature / blood*
Infusions, Intravenous
Male
Predictive Value of Tests
Prospective Studies
Reproducibility of Results
Single-Blind Method
Chemical
Reg. No./Substance:
58-08-2/Caffeine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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