Time dependent expression of MDR-1 in stable male renal transplant recipients

Abstract

Background/Aim Multi‐drug resistance (MDR‐1) expression during immunosuppressive therapy (IT) may influence individual drug response in renal transplant patients (RTR). However, no data exist that quantitate MDR‐1 in peripheral mononuclear cells (PBMCs) over IT interval. This was a pilot study in stable RTR to assess MDR‐1 expression in PBMCs before and after IT. Methods An observational study was done in 30 male RTR (ages 24–68 yrs) from a transplant clinic who were stable, > 6 months post‐transplant and receiving cyclosporine (trough: 50 ‐ 300 ng /ml), mycophenolate mofetil and prednisone. At time 0 (prior to IT) & 4 hours after IT, PBMCs were collected for analysis of MDR‐1 by quantitative real time‐polymerase chain reaction (QRT‐PCR). The target MDR‐1 PCR product was cloned, and verified by sequencing. The cloned MDR‐1 was used to establish standard curves (linearr2=0.996)and PCR efficiencies. QRT‐PCR data were normalized using the mean of 3 housekeeping genes: B‐actin, cyclophilin, GAPDH. Results In RTR (15 African American; 15 Caucasian), MDR‐1 expression ranged at time 0 from 11 to 613×10 6 copies (2 orders of magnitude difference) and at 4 hours from 6.6 to 1700×106 copies (3 orders of magnitude difference). MDR‐1 expression differed between time (0 hr= 129.8±132.97×106 vs. 4 hr= 188.7±424.0×10 6 copies; p<0.0001) with no racial difference. Conclusion Notable interpatient variability exists for MDR‐1 expression on PBMCs in RTR with differential expression prior to and following IT. Clinical Pharmacology & Therapeutics (2005) 77, P62–P62; doi: