High intra-patient variability (IPV) of tacrolimus levels is associated with poor long-term outcome after transplantation. We aimed to evaluate whether the number of regularly prescribed medications is associated with the tacrolimus IPV. We have studied 152 kidney transplant recipients (KTRs) with mean post-transplant time of 6.0 ± 3.1 years. The coefficient of variation (CV) as a measure of IPV was calculated in each individual patient. Data concerning the type and number of currently prescribed medications were collected. The participants were divided into four groups, based on the number of regularly prescribed drugs (≤3, 4-6, 7-9, ≥10 drugs, respectively). There was an increasing trend for median CV, proportional to the increasing number of medications [group 1: 0.11 (interquartile range, 0.08-0.14), group 2: 0.14 (0.01-0.17), group 3: 0.17 (0.14-0.23), group 4: 0.17 (0.15-0.30); p value for trend = 0.001]. Stepwise backward multivariate regression analysis revealed that the number of medications [partial correlation coefficient (rpartial) = 0.503, p < 0.001] independently influenced the tacrolimus IPV. Concomitant steroid or diuretics use increased IPV only in Advagraf-treated KTRs, whereas proton-pump inhibitor or statin use increased IPV in the Prograf group but not in the Advagraf group. A large number of concomitant medications significantly increases the tacrolimus IPV in stable KTRs.
Keywords: chronic kidney disease; co-medication; coefficient of variation; drug interactions; extended-release tacrolimus; number of medications; tacrolimus formulation.