Pankaj K Sethi1,2, Catherine A White1, Brian S Cummings1, Ronald N Hines3,4,5, Srinivasa Muralidhara1, James V Bruckner1. 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.
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.
Authors: Sevasti B Koukouritaki; Jason R Manro; Sandra A Marsh; Jeffrey C Stevens; Allan E Rettie; D Gail McCarver; Ronald N Hines Journal: J Pharmacol Exp Ther Date: 2003-11-21 Impact factor: 4.030
Authors: Stephanie Laeer; Willi Cawello; Bjoern B Burckhardt; László Ablonczy; Milica Bajcetic; Johannes M P J Breur; Michiel Dalinghaus; Christoph Male; Saskia N de Wildt; Jörg Breitkreutz; Muhammed Faisal; Anne Keatley-Clarke; Ingrid Klingmann; Florian B Lagler Journal: Pharmaceutics Date: 2022-05-30 Impact factor: 6.525
Authors: Pankaj K Sethi; Catherine A White; Brian S Cummings; Ronald N Hines; Srinivasa Muralidhara; James V Bruckner Journal: Pediatr Res Date: 2015-11-16 Impact factor: 3.756
Authors: Pankajini Mallick; Marjory Moreau; Gina Song; Alina Y Efremenko; Salil N Pendse; Moire R Creek; Thomas G Osimitz; Ronald N Hines; Paul Hinderliter; Harvey J Clewell; Brian G Lake; Miyoung Yoon Journal: Toxicol Sci Date: 2020-01-01 Impact factor: 4.849
Authors: Elisa A M Calvier; Elke H J Krekels; Pyry A J Välitalo; Amin Rostami-Hodjegan; Dick Tibboel; Meindert Danhof; Catherijne A J Knibbe Journal: Clin Pharmacokinet Date: 2017-03 Impact factor: 6.447