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PMCID: PMC5017908 DOI: 10.1002/cpt.409


Protein expression of major hepatic uptake and efflux drug transporters in human pediatric (n = 69) and adult (n = 41) livers was quantified by liquid chromatography / tandem mass spectroscopy (LC-MS/MS). Transporter protein expression of OCT1, OATP1B3, P-gp, and MRP3 was age-dependent. Particularly, significant differences were observed in transporter expression (P < 0.05) between the following age groups: neonates vs. adults (OCT1, OATP1B3, P-gp), neonates or infants vs. adolescents and/or adults (OCT1, OATP1B3, and P-gp), infants vs. children (OATP1B3 and P-gp), and adolescents vs. adults (MRP3). OCT1 showed the largest increase, of almost 5-fold, in protein expression with age. Ontogenic expression of OATP1B1 was confounded by genotype and was revealed only in livers harboring SLCO1B1*1A/*1A. In livers >1 year, tissues harboring SLCO1B1*14/*1A showed 2.5-fold higher (P < 0.05) protein expression than SLCO1B1*15/*1A. Integration of these ontogeny data in physiologically based pharmacokinetic (PBPK) models will be a crucial step in predicting hepatic drug disposition in children.

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Clinical pharmacology and therapeutics





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MeSH Keywords

ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily G, Member 2; Adolescent; Aging; Child; Child, Preschool; Genotype; Humans; Infant; Infant, Newborn; Liver; Liver-Specific Organic Anion Transporter 1; Multidrug Resistance-Associated Proteins; Neoplasm Proteins; Organic Anion Transporters, Sodium-Independent; Organic Cation Transporter 1; Polymorphism, Single Nucleotide; Proteomics; Solute Carrier Organic Anion Transporter Family Member 1B3