title: Effect of mycophenolate mofetil on hematological side effects incidence in renal transplant recipients.
abstract: Mycophenolate mofetil (MMF), an immunosuppressant administered after solid organ transplantation, is generally well tolerated; however, it frequently causes hematological toxicity. In this study, we aimed to assess the relation between the pharmacokinetic parameters of MMF metabolites (mycophenolic acid [MPA] and 7-O-MPA glucuronide [MPAG]) and the adverse effects on the hematopoietic system in renal transplant recipients. The four-h pharmacokinetic profiles of MPA and MPAG were determined using the HPLC method for MMF-treated patients (n = 61) among 106 renal transplant recipients (during the late post-transplant period) participating in the study. Anemia was more frequently observed in the study group compared with the control group (30.7% vs. 20.0%) and although the difference was insignificant, plasma iron concentrations were significantly higher in patients treated with MMF (32.9 ± 9.4 μmol/L vs. 28.7 ± 9.4 μmol/L; p = 0.032). Iron supplementation was more frequently applied to patients with anemia (48.2%) compared with patients with hemoglobin within the norm (20.3%; p = 0.005). As all MPAG pharmacokinetic parameters correlated negatively with hemoglobin and hematocrit, and MPAG pharmacokinetic parameters were higher in patients with anemia, MPAG may be the predicting factor of MMF side effects. In renal transplant recipients, especially with deteriorated renal function, extensive iron supplementation may be ineffective as anemia was associated with declined renal function and was not caused by low iron concentration.
authors.affiliation: Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Sobiak
authors.forename: Jolanta
authors.initials: J
authors.lastname: Kamińska
authors.forename: Maciej
authors.initials: M
authors.lastname: Głyda
authors.forename: Grażyna
authors.initials: G
authors.lastname: Duda
authors.forename: Maria
authors.initials: M
authors.lastname: Chrzanowska
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced / Q000453:epidemiology*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006413:Hematopoietic System / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives*; D011379:Prognosis; D012307:Risk Factors; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid
keywords: hematological side effects; mycophenolate mofetil; pharmacokinetics; post-transplantation anemia; renal transplantation