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Becquemont, L. et al.

Becquemont, Camus, Eschwege, Barbu, Rey, Funck-Brentano, Jaillon,

Lymphocyte P-glycoprotein expression and activity before and after rifampicin in man.

It has recently been shown that P-glycoprotein (P-gp) is inducible by rifampicin in the human gut as shown in intestinal biopsies. The present study was performed in order to test the hypothesis that human peripheral lymphocytes can be used to assess such an inducibility. We also assessed inter- and intra-individual variability of P-gp expression and activity in peripheral lymphocytes. Blood samples from 13 healthy volunteers were collected 1.7, 14 and 19 days after inclusion. Rifampicin treatment (600 mg/day) was administered from day 15 to day 18. Lymphocyte P-gp expression was measured at the messenger RNA level by semi-quantitative RT-PCR and at the protein level by immunostaining flow cytometry. P-gp activity was determined by flow cytometry with rhodamine 123 efflux. Cytochrome P4503A4 (CYP3A4) inducibility was measured by comparing the urinary metabolic ratio of 6beta-hydroxycortisol/cortisol on day 14 and 19, Lymphocyte P-gp expression and activity was not induced by rifampicin, while it increased CYP3A4 activity from 5.0 +/- 4.0 to 22.9 +/- 16.6 (P < 0.001). There was a 3 - 4-fold inter-individual variability and a 3 - 44 % intra-individual variability of lymphocyte P-gp expression and activity. Peripheral lymphocytes are not an appropriate material to assess P-gp inducibility in humans. P-gp shows significant inter- and intra-individual variability in human lymphocytes.[1]

References

Lymphocyte P-glycoprotein expression and activity before and after rifampicin in man. Becquemont, L., Camus, M., Eschwege, V., Barbu, V., Rey, E., Funck-Brentano, C., Jaillon, P. Fundamental & clinical pharmacology. (2000) [Pubmed]

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