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Research ArticleSpecial Section on Pediatric Drug Disposition and Pharmacokinetics

Expression Patterns of Organic Anion Transporting Polypeptides 1B1 and 1B3 Protein in Human Pediatric Liver

Margaret M. S. Thomson, Ronald N. Hines, Erin G. Schuetz and Bernd Meibohm
Drug Metabolism and Disposition July 2016, 44 (7) 999-1004; DOI: https://doi.org/10.1124/dmd.115.069252
Margaret M. S. Thomson
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee (M.M.S.T., B.M.); Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin (R.N.H.); and Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital Memphis, Tennessee (E.G.S.)
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Ronald N. Hines
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee (M.M.S.T., B.M.); Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin (R.N.H.); and Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital Memphis, Tennessee (E.G.S.)
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Erin G. Schuetz
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee (M.M.S.T., B.M.); Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin (R.N.H.); and Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital Memphis, Tennessee (E.G.S.)
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Bernd Meibohm
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee (M.M.S.T., B.M.); Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin (R.N.H.); and Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital Memphis, Tennessee (E.G.S.)
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    Fig. 1.

    Representative Western blot analysis of OATP1B1 and OAT1B3 in pediatric liver specimens. Lane 1, positive control for OATP1B3; lane 2, molecular ladder; lane 3, positive control for OATP1B1; lanes 4–6, pediatric liver specimens.

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    Fig. 2.

    Relative OATP1B protein expression (normalized to GAPDH) in pediatric liver for different age groups (group A, <3 months; group B, 3 months to <2 years; group C, 2 to <6 years; group D, 6–12 years), as follows: highly glycosylated OATP1B3 (A); core-glycosylated OATP1B3 (B); total (highly glycosylated and core-glycosylated) OATP1B3 (C); and OATP1B1 (D). Boxes represent the interquartile range, whiskers represent the 10th and 90th percentiles. The solid horizontal line in the box denotes the median, and the dotted line represents the mean of the data.

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    Fig. 3.

    Relative OATP1B protein expression (normalized to GAPDH) in pediatric liver versus postnatal age. The x-axis is discontinuous, with ages less than 1 year shown as a fraction. Highly glycosylated OATP1B3 (A), core-glycosylated OATP1B3 (B), total (highly glycosylated and core-glycosylated) OATP1B3 (C), and OATP1B1 (D).

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    TABLE 1

    Demographic information of study individuals

    Demographic InformationValues
    Postnatal Age (N)80
    Age Range9 days – 12 yr
    Mean Age (SD)3.53 yr (3.86 yr)
    Sex (N)
     Male43
     Female27
     Unknown10
    Race (N)
     Caucasian43
     African-American20
     Other5
     Unknown12
    Source (N)
     Living Donor32
     Post Mortem48
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    TABLE 2

    Relative OATP1B protein expression in different age groups investigated in this study

    Age Groups
    ABCD
    Postnatal Age Range<3 mo3 mo to <2 yr2 to <6 yr6–12 yr
    N20211722
    Mean age (yr)0.1280.7153.739.14
    S.D. (yr)0.0670.4121.131.67
    Highly Glycosylated OATP1B3
     Geometric Mean1.49**B,*C0.210*D0.3200.637
     25th to 75th percentile0.801–2.790.028–1.050.267–0.7630.223–3.31
     Relative to Group D235%33%50%100%
    Core-Glycosylated OATP1B3
     Geometric Mean3.59**B,**C,*D0.4950.3990.710
     25th to 75th percentile2.41–5.110.240–2.170.319–1.110.471–2.08
     Relative to Group D505%70%56%100%
    Total OATP1B3
     Geometric Mean5.31**B,**C,*D0.9560.8731.49
     25th to 75th percentile3.33–7.860.412–3.370.720–2.210.671–4.95
     Relative to Group D357%64%59%100%
    OAPT1B1
     Geometric Mean0.05350.04450.02770.139
     25th to 75th percentile0.0045–0.2960.0107–0.1960.0155–0.09470.0275–0.871
     Relative to Group D38%32%20%100%
    • Statistically significant differences are marked with asterisks (*P ≤ 0.05 and **P < 0.01); superscript letters denote the comparison group.

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Drug Metabolism and Disposition: 44 (7)
Drug Metabolism and Disposition
Vol. 44, Issue 7
1 Jul 2016
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Research ArticleSpecial Section on Pediatric Drug Disposition and Pharmacokinetics

Ontogeny of Organic Anion Transporting Polypeptide in Liver

Margaret M. S. Thomson, Ronald N. Hines, Erin G. Schuetz and Bernd Meibohm
Drug Metabolism and Disposition July 1, 2016, 44 (7) 999-1004; DOI: https://doi.org/10.1124/dmd.115.069252

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Research ArticleSpecial Section on Pediatric Drug Disposition and Pharmacokinetics

Ontogeny of Organic Anion Transporting Polypeptide in Liver

Margaret M. S. Thomson, Ronald N. Hines, Erin G. Schuetz and Bernd Meibohm
Drug Metabolism and Disposition July 1, 2016, 44 (7) 999-1004; DOI: https://doi.org/10.1124/dmd.115.069252
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