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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kagaya, H. Miura, M. Satoh, S. Inoue, K. Saito, M. Inoue, T. Habuchi, T. Suzuki, T. |
| Description | Country affiliation: Japan Author Affiliation: Kagaya H ( Department of Pharmacy, Akita University Hospital, Akita, Japan.) |
| Abstract | OBJECTIVE: The aim of this study was to investigate drug interactions between mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF) and tacrolimus, as well as the impact of CYP3A5 and UGT2B7 genetic polymorphisms on these drug interactions in 71 Japanese renal transplant recipients. METHODS: Recipients received combination immunosuppressive therapy consisting of tacrolimus and MMF. On day 28 after transplantation, the concentrations of MPA and tacrolimus were measured by high-performance liquid chromatography and microparticle enzyme immunoassay respectively. RESULTS: Acute rejection was over twice more common in recipients with a total area under the observed plasma concentration-time curve (AUC(0-12)) of MPA <70 microg x h/mL than in those with higher values AUC(0-12) values (17% vs. 7%). Using this cut-off AUC value, sensitivity was 70.6% and specificity 55.6% for acute rejection (AR). There was no change in AUC(0-12), maximum plasma concentration, trough plasma concentration, or oral clearance of tacrolimus with variation in dosage or AUC of MPA. There were also no significant differences in the MPA pharmacokinetic parameters among three tacrolimus C(0) groups: 5 < or = C(0) < 10, 10 < or = C(0) < 15 and 15 < or =C(0) < 20 ng/mL. Furthermore, there were no significant differences in MPA pharmacokinetic parameters between the UGT2B7*1/*1 and *1/*2 genotype groups having the CYP3A5*1 allele or the CYP3A5*3/*3 genotype. CONCLUSION: Therapeutic dosages of MMF, do not significantly influence tacrolimus pharmacokinetics, and vice versa. Consequently, MPA and tacrolimus can be safely combined; however, it is necessary to monitor the plasma concentrations of each immunosuppressive agent to minimize acute rejection. |
| File Format | HTM / HTML |
| ISSN | 02694727 |
| Issue Number | 2 |
| Volume Number | 33 |
| e-ISSN | 13652710 |
| Journal | Journal of Clinical Pharmacy and Therapeutics |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2008-04-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Subscribed |
| Subject Keyword | Discipline Therapeutics Discipline Pharmacology Immunosuppressive Agents Pharmacokinetics Kidney Transplantation Mycophenolic Acid Analogs & Derivatives Blood Prodrugs Tacrolimus Adult Area Under Curve Asian Continental Ancestry Group Genetics Cytochrome P-450 Cyp3a Cytochrome P-450 Enzyme System Drug Interactions Female Genotype Glucuronosyltransferase Humans Therapeutic Use Male Polymorphism, Genetic Clinical Trial Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology Pharmacology (medical) |
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