Metabolising enzymes and transport proteins are largely expressed in human tissues. They have major impact on drug disposition and effects. We studied mRNA expression of phase I and II metabolising enzymes and transporters in fetal tissues at different development stages. Hepatic, duodenal, renal and neurological fetal tissues were studied at 15, 27 and 42 weeks gestation and mRNA expression of 84 enzymes and transporters was analysed by with the RT(2) Profiler PCR array system. There was wide variability in gene expression between different samples. Independently from age, the highest expression levels were observed in the liver and the lowest in the brain for the majority of genes tested. There was significant increase in gene expression with age in duodenal and hepatic tissues.

Pharmacogenetic polymorphisms that change the amino acid sequences in coding regions only account for part of the interindividual differences in disease susceptibility and drug response. Additional pharmacogenomic and epigenetic factors are also involved. In children, pharmacogenetic studies are limited, although it has been clear for many years that the interactions between developmental patterns of drug-metabolizing enzymes and transporters have a major impact on dose exposure with age-specific dosage requirements. This article will analyze the factors affecting variability in drug response in children and focus on the pharmacogenetic polymorphisms of immunosuppressants, antidepressants, anticancer and anti-inflammatory drugs. Additional pharmacogenetic and epigenetic studies should be performed to allow the individualization of therapy in children.

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