Manuscript for Drug Metabolism and Disposition Title Developmental changes in hepatic OCT1 protein expression from neonates to children

Abstract

Abstract Organic cation transporter 1 (OCT1) plays an important role in the disposition of clinicallyimportant drugs, and the capacity of OCT1 activity is presumed to be proportional to the protein expression level in organ tissues. Presently, knowledge of OCT1 protein expression in children is very limited, especially among neonates and small infants. Here, we report on the characterization of OCT1 protein expression in neonatal, infant and pediatric liver samples performed by Immunoblot analysis. OCT1 protein expression was detected in liver samples from neonates as early as postnatal day 1 -2. This youngest group showed significantly lower OCT1 expression normalized by GAPDH (0.03 ±0.02 arbitrary unit (AU), mean ± SD, N=7) compared to samples aged 3 -4 weeks (0.08 ±0.03 AU, N=5, **P< 0.01), 3 -6 months (0.23 ± 0.15 AU, N=7, **P< 0.01), 11 months -1 year (0.42 ± 0.32 AU, N=6, **P< 0.01), and 8 -12 years (1.00 ± 0.44 AU, N=7, **P< 0.01). These data demonstrate an age-dependent increase in OCT1 expression from birth up to 8-12 years of age, and the findings of this study contribute to the understanding of OCT1 functional capacity and their effect of the disposition of OCT1 substrates in neonates and small infants

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