Gender Differences in Pharmacokinetics of Tacrolimus and Their Clinical Significance in Kidney Transplant Recipients

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The possible influence of gender on tacrolimus disposition and response in kidney transplant recipients is an issue of medical importance. The aim of this study was to detect interpatient pharmacokinetic variability of tacrolimus due to patients' gender and to assess the predictability of individual tacrolimus concentrations using abbreviated AUC measurements. The secondary objective was to find the best sampling time to predict the exposure of tacrolimus in kidney transplant recipients. Gender-related first oral dose tacrolimus pharmacokinetics studies were conducted in 20 Serbian kidney transplant recipients (10 men/10 women) on quaternary immunosuppressive therapy. The first tacrolimus oral dose (0.05 mg/kg) was given on day 5 post-transplant. Blood concentrations were measured by microparticle enzyme immunoassay method. Associations between each sampling time point of concentrations and 12 hours after the administration AUC (AUC(0-12)) were evaluated by Pearson correlation coefficients. Abbreviated sampling equations were derived by multiple stepwise regression analyses. AUC(0-12) showed remarkable interindividual variations after the first tacrolimus oral dose. There were significantly lower values of AUC in women than men (P < 0.05). The most important time point influencing AUC(0-12) was the concentration of tacrolimus measured 2 hours after administration(C(2)) in women, whereas in men the most important time points were the concentrations at 1 (C(1)), 4 (C(4)), and 12 (C(12)) hours as an abbreviated AUC. Our results show significant differences between men and women. C(2) seems to be indicator of total body exposure to tacrolimus in the early period after kidney transplant in women. The three-point sampling method seems to be a good indicator of abbreviated AUC for a tacrolimus monitoring strategy in men.