The pharmacokinetics of a single oral dose of mycophenolate mofetil in patients with varying degrees of renal function
| Autor: | Suzanne K. Swan, Heather J. Johnson, Andrew J. Nicholls, Karen L. Heim-Duthoy, Thomas Tarnowski, Irene Tsina |
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| Rok vydání: | 1998 |
| Předmět: |
Adult
Male Metabolic Clearance Rate medicine.medical_treatment Cmax Renal function Administration Oral Pharmacology Mycophenolate Mycophenolic acid Pharmacokinetics Oral administration Renal Dialysis medicine Humans Pharmacology (medical) Prodrugs Renal Insufficiency Analysis of Variance Chemistry Middle Aged Mycophenolic Acid Area Under Curve Toxicity Female Hemodialysis Immunosuppressive Agents medicine.drug Glomerular Filtration Rate Half-Life |
| Zdroj: | Clinical pharmacology and therapeutics. 63(5) |
| ISSN: | 0009-9236 |
| Popis: | Background The purpose of this study was to determine the effect of renal function on the elimination and disposition of mycophenolic acid and its glucuronide metabolite (MPAG) after oral administration of the pro-drug mycophenolate mofetil. In addition, this study sought to examine hemodialysis removal of mycophenolic acid and its MPAG. Methods Subjects were stratified into five groups on the basis of iohexol clearance. After an overnight fast, all subjects received a single 1 gm dose of mycophenolate mofetil. Plasma concentrations of mycophenolic acid and MPAG were measured from 0 to 96 hours after administration. Mycophenolic acid and MPAG maximum plasma concentration (Cmax) and the time to reach Cmax (tmax) for each group were determined from the mean plasma concentration-time profiles. Area under the plasma concentration-time curve values for mycophenolic acid and MPAG were calculated by the trapezoidal rule. The half-lives of mycophenolic acid and MPAG were calculated from the terminal portions of the concentration-time profiles. Results Mycophenolic acid clearance was not associated with changes in glomerular filtration rate (GFR). Cmax tended to increase as GFR declined. MPAG clearance correlated well with GFR (r2 = 0.905). Clearance of mycophenolic acid and MPAG were unaffected by hemodialysis. Conclusions Clearance of mycophenolic acid after a single 1 gm oral dose of mycophenolate mofetil is unaffected by renal function. Clearance of mycophenolic acid is unaffected by hemodialysis. Diminished renal function should not require preemptive adjustment of 1 gm doses of mycophenolate mofetil; however, dosage adjustment may be warranted on the basis of adverse effects or toxicity in individual patients. Mycophenolate mofetil can be administered irrespective of hemodialysis session without effect on mycophenolic acid exposure. Clinical Pharmacology & Therapeutics (1998) 63, 512–518; doi |
| Databáze: | OpenAIRE |
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