Influence of Metal Cations on Plasma Trough Concentration of Mycophenolic Acid and Its Glucuronide in Tacrolimus-Treated and Cyclosporine-Treated Kidney Transplant Recipients
| Autor: | Takafumi Naito, Atsushi Otsuka, Junichi Kawakami, Yasuaki Mino, Tomomi Ushiyama, Seiichiro Ozono, Yoshiyuki Kagawa |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Metabolite Urology Pharmaceutical Science Pharmacology Mycophenolate Tacrolimus Mycophenolic acid chemistry.chemical_compound Glucuronides Pharmacokinetics medicine Humans Drug Interactions Biotransformation Aged Antibiotics Antineoplastic General Medicine Middle Aged Mycophenolic Acid Drug interaction Kidney Transplantation Calcineurin stomatognathic diseases chemistry Metals Concomitant Cyclosporine Regression Analysis Female Immunosuppressive Agents medicine.drug |
| Zdroj: | Biological and Pharmaceutical Bulletin. 31:1292-1296 |
| ISSN: | 1347-5215 0918-6158 |
| DOI: | 10.1248/bpb.31.1292 |
| Popis: | The aim of this study was to evaluate the plasma trough concentrations (C(0)) of mycophenolic acid (MPA) and its major metabolite MPA 7-O-glucuronide (MPAG) in metal cation (MC)(-) (non-treated) and MC(+) (co-treated) patients who received tacrolimus (Tac) or cyclosporine (CyA). Fifty-nine Japanese stable kidney transplant recipients receiving immunosuppressive regimens containing mycophenolate mofetil (MMF) and a calcineurin inhibitor (CNI) were included in this study. Seven in the 25 patients receiving Tac and 8 in the 34 patients receiving CyA were treated with concomitant MCs administration. Multiple regression analysis revealed that concomitant MCs and CyA administration influenced MPA C(0). Their standardized partial regression coefficients were -0.29 and -0.41, respectively. Stratified analysis based on CNI treatment revealed that MPA C(0) decreased significantly by 56% with concomitant MCs administration in Tac-treated patients. There was no significant difference in MPA C(0) between the MC(-) and MC(+) groups in CyA-treated patients. With respect to MPAG C(0), MC(+) group tended to be lower by 26% than MC(-) group in Tac-treated patients. There was no significant difference in MPAG C(0) between the MC(-) and MC(+) groups in CyA-treated patients. Concomitant MCs administration did not affect the C(0) ratio of MPAG to MPA in either Tac- or CyA-treated patients. In conclusion, MCs co-administration decrease MPA C(0) in patients receiving Tac and may cause lower MPA exposure. There are little pharmacokinetic interactions between MMF and concomitant MCs in CyA-treated patients. |
| Databáze: | OpenAIRE |
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