title: Tacrolimus as a part of immunosuppressive treatment in kidney transplantation patients: sex differences.
abstract: BACKGROUND
  Metabolism interaction between corticosteroids and tacrolimus (Tac) exists and can be an important factor in providing rational pharmacotherapy in kidney transplantation patients. Both Tac and corticosteroids can induce adverse metabolic effects, such as hyperglycemia, post-transplantation diabetes mellitus, and dyslipidemia.
  
  
  OBJECTIVE
  The main goal of this study was to detect corticosteroid dose influence on Tac level within the first 6 months of immunosuppressive therapy. The secondary goal of this research was to investigate sex differences on Tac-corticosteroid interaction. We also monitored biochemical-parameter changes, which are related to immunosuppressive treatment.
  
  
  METHODS
  This retrospective pharmacokinetic study included 30 Serbian patients after kidney transplantation. Patients received a quaternary immunosuppressive regimen including Tac, mycophenolate, mofetil, basiliximab, and corticosteroids. To compare dose-normalized level and dose of Tac in different days after transplantation, we performed the Friedman test and Wilcoxon matched-pairs signed rank sum test. Mann-Whitney test was performed to compare differences in dose of Tac, level of Tac, and dose-normalized level of Tac between male and female patient groups. We used the Friedman test to compare biological and clinical data.
  
  
  RESULTS
  Obtained results show statistical significance between dose of Tac on day 180 post transplantation and dose on days 7, 14, 21, and 60 post transplantation. There was a statistical difference in dose-normalized level of Tac between days 7 and 21 post transplantation (P < 0.01), days 7 and 60 (P < 0.01), and between days 7 and 180 (P < 0.05). There is a statistical significance between male and female levels of Tac on day 21 after transplantation (P < 0.01). Significance also exists on day 60 after transplantation between male and female dose-normalized levels (P < 0.05). There is also a statistical difference in glucose, cholesterol, triglyceride, serum creatinine, and urea level and activity of alanine aminotransferase and alkaline phosphatase before and after operation.
  
  
  CONCLUSIONS
  Our study shows that dose of corticosteroid affects Tac level in kidney transplantation patients. Tac dose and level changes showed that corticosteroid-Tac interaction has more influence on male than female patients. According to biochemical monitoring, the immunosuppressive therapy used at present is quite well tolerated.
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Nis, Bulevar dr Zorana Djindjica 81, Nis, Serbia. farmakoterapija@yahoo.com
authors.forename: Radmila
authors.initials: R
authors.lastname: Velickovic-Radovanovic
authors.forename: Momir
authors.initials: M
authors.lastname: Mikov
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Catic-Djordjevic
authors.forename: Nikola
authors.initials: N
authors.lastname: Stefanovic
authors.forename: Mariola
authors.initials: M
authors.lastname: Stojanovic
authors.forename: Milan
authors.initials: M
authors.lastname: Jokanovic
authors.forename: Tatjana
authors.initials: T
authors.lastname: Cvetkovic
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000627:therapeutic use; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D056808:Biostatistics; D001786:Blood Glucose; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012737:Sex Factors; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood; D014508:Urea / Q000097:blood
chemical_list: D000305:Adrenal Cortex Hormones; D001786:Blood Glucose; D007166:Immunosuppressive Agents; D014280:Triglycerides; D014508:Urea; D002784:Cholesterol; D003404:Creatinine; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D016559:Tacrolimus