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Pediatr Res. 2016 Mar;79(3):409-15. doi: 10.1038/pr.2015.237. Epub 2015 Nov 16.

Ontogeny of plasma proteins, albumin and binding of diazepam, cyclosporine, and deltamethrin.

Author information

1
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia.
2
Current address: National Exposure Research Laboratory, U.S. Environmental Protection Agency, Athens, Georgia.
3
Department of Pediatrics, Medical College of Wisconsin, and Children's Research Institute, Children's Hospital and Health Systems, Milwaukee, Wisconsin.
4
Department of Pharmacology and Toxicology, Medical College of Wisconsin, and Children's Research Institute, Children's Hospital and Health Systems, Milwaukee, Wisconsin.
5
Current address: National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC.

Abstract

BACKGROUND:

To characterize the ontogeny of plasma albumin and total proteins, due to the lack of a comprehensive pediatric database. Secondly, to establish the magnitude and duration of maturational changes in binding of highly-bound drugs/chemicals.

METHODS:

Anonymized plasma samples from 296 donors were pooled in 6 age brackets from birth to adolescence. Total protein and albumin levels were measured in each age group, as was the age-dependency of plasma binding of diazepam (DZP), cyclosporine (CYC), and deltamethrin (DLM), a pyrethroid insecticide.

RESULTS:

Plasma levels of albumin and total proteins steadily increased for the first 1-3 y of life. Unbound DZP and CYC fractions were elevated three- to fourfold in neonates, but decreased to adult levels after 1 and 3 y, respectively. Unbound DLM levels exceeded those in adults for just 1 mo.

CONCLUSION:

Neonates and infants under 1-3 y may be at risk from increased amounts of free drug, when given standard doses of some highly-bound drugs. Pyrethroid insecticides might be anticipated to pose increased risk for 1 mo.

PMID:
26571224
DOI:
10.1038/pr.2015.237
[Indexed for MEDLINE]

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