High Levels of P-Glycoprotein Activity in Human Lymphocytes in the First 6 Months of Life

P-glycoprotein (P-gp) is an efflux transporter that controls the intracellular concentrations of drugs. Human development may modulate P-gp function. We investigated the effect of age on P-gp activity and MDR1 gene expression in lymphocytes. We also assessed the influence of human immunodeficiency virus (HIV) infection. We used 3,3′-diethyloxacarbocyanin iodide (DiOC6) efflux, estimated by flow cytometry, to quantify P-gp activity in 94 children (age range, 0–18 years) and 25 adults. MDR1 gene expression was quantified using reverse transcription–PCR (RT-PCR). In T and natural killer (NK) cell populations, P-gp activity peaked at birth, decreased between the ages of 0 and 6 months, and stabilized between the ages of 6 months and 2 years (P < 10−6). These maturation profiles were also strongly correlated (r = 0.67, P < 10−6). HIV infection did not affect P-gp activity in the lymphocytes of children. MDR1 gene expression was not influenced by age, nor was it correlated with P-gp activity. The high levels of P-gp activity observed in the lymphocytes of children ~6 months of age may affect the efficacy of intracellular drugs. Clinical Pharmacology & Therapeutics (2009); 85, 3, 289–295 doi:10.1038/clpt.2008.221