Causes and Consequences of Variability in Drug Transporter Activity in Pediatric Drug Therapy.

摘要: Drug transporters play a key role in mediating the uptake of endo- and exogenous substances into cells as well their efflux. Therefore, variability drug transporter activity can influence pharmaco- toxicokinetics be determinant safety efficacy. In children, particularly neonates young infants, contribution tissue-specific to absorption, distribution, excretion may differ from that adults. this review 5 major factors interdependence children are discussed: developmental differences, genetic polymorphisms, pediatric comorbidities, interacting comedication, environmental factors. Even if data sparse, altered due those have been associated with clinically relevant differences disposition, efficacy, patients. Single nucleotide polymorphisms transporter-encoding genes were most studied source children. However, age group where has reported adults, namely hardly any studies performed. Longitudinal population required investigate age- disease-dependent genotype-phenotype relationships relevance drug-drug interactions. Physiologically based pharmacokinetic modeling approaches integrate drug- patient-specific parameters, including ontogeny, further improve silico predictions pediatric-specific pharmacokinetics.