title: The influence of comedication on tacrolimus blood concentration in patients subjected to kidney transplantation: a retrospective study.
abstract: Tacrolimus is an immunosuppressant used for the prevention of kidney allograft rejection. The effects of comedication on tacrolimus trough concentrations (TTC) in kidney transplant recipients, subjected to basic immunosuppressant regime consisting of tacrolimus, corticosteroids and mycophenolate mofetil were investigated. This retrospective case series study involved 208 of these patients, with the outpatient examination recorded in the database of patients, at the unit of monitoring, with a total of 5,011 such examinations. Binary logistic regression analysis has shown that calcium channel blockers, diuretics and proton pump inhibitors (PPIs) significantly affected TTC (p < 0.001). PPIs significantly increased the number of examinations in which the TTC were in the recommended therapeutic range (from 5 to 15 ng/ml), as well as over the therapeutic range (p < 0.0001). When calcium channel blockers were added to PPIs, even more pronounced effect was obtained in comparison to triple-drug therapy only (p < 0.0001). In case a diuretic was given with a PPI, a significantly increased number of examinations with subtherapeutic TTC was observed when compared with PPI only (p = 0.0203). The combination of calcium channel blockers, diuretics and PPIs resulted in the number of examinations with TTC in the recommended therapeutic range not being different from the number of examinations with TTC in the triple-drug therapy only (p = 0.3829). β-adrenergic antagonists can be administered without fear of affecting the tacrolimus optimal therapeutic concentrations. This was confirmed with all combinations of the examined drugs used in patients subjected to kidney transplantation concomitantly with β blockers.
authors.affiliation: Centre for Transplantation of Solid Organs, Military Medical Academy, Belgrade, Serbia.
authors.forename: Neven
authors.initials: N
authors.lastname: Vavic
authors.forename: Nemanja
authors.initials: N
authors.lastname: Rancic
authors.forename: Viktorija
authors.initials: V
authors.lastname: Dragojevic-Simic
authors.forename: Biljana
authors.initials: B
authors.lastname: Draskovic-Pavlovic
authors.forename: Dubravko
authors.initials: D
authors.lastname: Bokonjic
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Ignjatovic
authors.forename: Momir
authors.initials: M
authors.lastname: Mikov
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016559:Tacrolimus / Q000097:blood*
chemical_list: D007166:Immunosuppressive Agents; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D016559:Tacrolimus