Developmental pharmacogenetics in pediatric rheumatology: utilizing a new paradigm to effectively treat patients with juvenile idiopathic arthritis with methotrexate.

Although methotrexate is widely used in clinical practice there remains significant lack of understanding of its mechanisms of action and the factors that contribute to the variability in toxicity and response seen clinically. In addition to differences in drug administration, factors that affect pharmacokinetics and pharmacodynamics such as genetic variation may explain individual differences in drug biotransformation. However, the pediatric population has an additional factor to consider, namely the ontogeny of gene expression which may result in variation throughout growth and development. We review the current understanding of methotrexate biotransformation and the concept of ontogeny, with further discussion of how to implement a developmental pharmacogenomics approach in future studies.