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2016, Number 6

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Gac Med Mex 2016; 152 (6)

Rheumatoid arthritis (RA) disease activity predicts function of ABCB1 (P-gp) and ABCG2 (BCRP1) drug-efflux transporters

Pascual-Ramos V, Atisha-Fregoso Y, Lima G, Fragoso-Loyo H, Jákez-Ocampo J, Contreras-Yáńez I, Llorente L

Language: Spanish
References: 49
Page: 741-754
PDF size: 299.60 Kb.


ABSTRACT

Background: P-gp and BCRP1 are transporter proteins that may confer drug resistance. Objective: To compare P-gp and BCRP1 function in rheumatoid arthritis patients with active and inactive disease and to define their relation with disease activity. Methods: We included 17 active patients paired (age, gender, disease duration) to 17 inactive patients. All had baseline evaluations and 27 had additional six-month follow-up. P-gp and BCRP1 functional activity was measured in peripheral mononuclear cells by flow cytometry. Percentage of lymphocytes able to extrude substrates for P-gp and BCRP1 were recorded in the presence/absence of selective inhibitors. Informed consent was obtained. Descriptive statistics and linear regression model were applied. Results: Active patients had higher efflux function of both transporters than inactive patients: median (25-75 IQR) P-gp of 7.1% (1.4-29.3) vs. 1.6% (0.7-3.5), p = 0.02 and BCRP1 of 6.2% (1.3-22.4) vs. 1.3% (0.7-2), p = 0.007. At baseline, disease activity was the only predictor of both transporter functions. At follow-up, changes in disease activity correlated with shift in P-gp (r = 0.35, p = 0.07) and BCRP1 (r = 0.33, p=0.09) function. Conclusions: Patients with active rheumatoid arthritis had a higher efflux function of P-gp and BCRP1 compared to inactive patients. The behavior of P-gp and BCRP1 appeared to be conditioned by disease activity.


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