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- Title
High levels of P-glycoprotein activity in human lymphocytes in the first 6 months of life.
- Authors
Giraud, C; Declèves, X; Perrot, J Y; Manceau, S; Pannier, E; Firtion, G; Morini, J P; Chappuy, H; Batteux, F; Chouzenoux, S; Scherrmann, J M; Blanche, S; Tréluyer, J M
- Abstract
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 (DiOC(6)) 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.
- Publication
Clinical pharmacology and therapeutics, 2009, Vol 85, Issue 3, p289
- ISSN
1532-6535
- Publication type
Journal Article
- DOI
10.1038/clpt.2008.221