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 rifam picin in the human gut as shown in intestinal biopsies. The present study w as performed in order to test the hypothesis that human peripheral lymphocy tes 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 admi nistered from day 15 to day Is. Lymphocyte P-gp expression was measured at the messenger RNA level by semi-quantitative RT-PCR and at the protein leve l by immunostaining flow cytometry. P-gp activity was determined by flow cy tometry with rhodamine 123 efflux. Cytochrome P4503A4 (CYP3A4) inducibility was measured by comparing the urinary metabolic ratio of 6 beta -hydroxyco rtisol/cortisol on day 14 and 19. Lymphocyte P-gp expression and activity w as 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 ex pression and activity. Peripheral lymphocytes are not an appropriate materi al to assess P-gp inducibility in humans. P-gp shows significant inter- and intra-individual variability in human lymphocytes. (C) 2000 Editions scien tifiques et medicales Elsevier SAS.