Tacrolimus as a Part of Immunosuppressive Treatment in Kidney Transplantation Patients: Sex Differences

• Published in: Gender medicine 2012-12, Vol.9 (6), p.471-480
• Main Authors: Velickovic-Radovanovic, Radmila, PhD, Mikov, Momir, PhD, Catic-Djordjevic, Aleksandra, PharmD, Stefanovic, Nikola, PharmD, Stojanovic, Mariola, MD, Jokanovic, Milan, PhD, Cvetkovic, Tatjana, PhD
• Format: Article
• Language: English
• Subjects: Adrenal Cortex Hormones - administration & dosage; Adrenal Cortex Hormones - therapeutic use; Adult; Alanine Transaminase - blood; Alkaline Phosphatase - blood; biochemical monitoring; Biological and medical sciences; Biostatistics; Blood Glucose; Cholesterol - blood; corticosteroid; Creatinine - blood; Drug Interactions; Female; Humans; Immunosuppressive Agents - blood; Immunosuppressive Agents - pharmacokinetics; Immunosuppressive Agents - therapeutic use; Internal Medicine; Kidney Transplantation; Male; Medical sciences; Middle Aged; Miscellaneous; pharmacokinetic interaction; Public health. Hygiene; Public health. Hygiene-occupational medicine; Retrospective Studies; Sex Factors; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the urinary system; tacrolimus; Tacrolimus - blood; Tacrolimus - pharmacokinetics; Tacrolimus - therapeutic use; Triglycerides - blood; Urea - blood
• ISSN: 1550-8579; 1878-7398
• DOI: 10.1016/j.genm.2012.10.003

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. Conclusion 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.