Journal
DRUG METABOLISM AND DISPOSITION
Volume 44, Issue 7, Pages 999-1004Publisher
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/dmd.115.069252
Keywords
-
Categories
Funding
- National Institutes of Health National Cancer Institute [R01-CA-53106]
- American Lebanese Syrian Associated Charities (ALSAC)
Ask authors/readers for more resources
Determining appropriate pharmacotherapy in young children can be challenging due to uncertainties in the development of drug disposition pathways. With knowledge of the ontogeny of drug-metabolizing enzymes and an emerging focus on drug transporters, the developmental pattern of the uptake transporters organic anion transporting polypeptide (OATP) 1B1 and 1B3 was assessed by relative protein quantification using Western blotting in 80 human pediatric liver specimens covering an age range from 9 days to 12 years. OATP1B3 exhibited high expression at birth, which declined over the first months of life, and then increased again in the preadolescent period. In comparison with children 6-12 years of age, the relative protein expression of highly glycosylated (total) OATP1B3 was 235% (357%) in children < 3 months of age, 33% (64%) in the age group from 3 months to 2 years, and 50% (59%) in children 2-6 years of age. The fraction of highly glycosylated to total OATP1B3 increased with age, indicating ontogenic processes not only at the transcriptional level but also at the post-translational level. Similar to OATP1B3, OATP1B1 showed high interindividual variability in relative protein expression but no statistically significant difference among the studied age groups.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available