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- Title
Population pharmacokinetics of mycophenolic acid during the first week after renal transplantation.
- Authors
Staatz, Christine E.; Duffull, Stephen B.; Kiberd, Bryce; Fraser, Albert D.; Tett, Susan E.
- Abstract
Objective: To investigate the population pharmacokinetics of mycophenolic acid (MPA) in adult kidney transplant recipients during the crucial first week after transplantation. Methods: Data were collected from 117 patients. MPA plasma concentrations were determined at t= 0, 1, 2, 3 and 4 h after mycophenolate mofetil dosing on days 3, 5 and 7. Population analysis was performed using NON- MEM. Covariates screened were sex, age, body weight, serum creatinine, creatinine clearance, serum albumin, days of therapy, diabetes mellitus, organ source (live or cadaveric) and co-therapy (tacrolimus or cyclosporine). Final model validity was evaluated using 200 bootstrapped samples from the original data. Bias and precision were determined through comparison of observed and predicted concentrations. Results: Individual concentration-time profiles showed evidence of an absorption lag time and enterohepatic recirculation of MPA in some patients on some occasions. The best base model had bi-exponential elimination with a typical population (SE%) apparent clearance (CL/F) of 29 1/h (5%) and apparent volume of the central compartment of 65 1 (7%). CL/F decreased significantly with increasing serum albumin (1.42 1/h reduction in total plasma CL/F with each 1 g/l increase in albumin) and was 27% greater in patients receiving cyclosporine than in those receiving tacrolimus. Evaluation of the final model showed close agreement between pairs of bootstrapped and final model parameter estimates (all differences <7%). Predictions were non- biased (0.11 mg/l) but imprecise (2.8 mg/l). Conclusion: Population pharmacokinetic parameters for MPA were determined. These can be used to achieve specific target MPA concentrations or areas under the concentration-time curve.
- Subjects
PHARMACOKINETICS; DRUG metabolism; TRANSPLANTATION of organs, tissues, etc.; BLOOD plasma; THERAPEUTICS; BODY weight
- Publication
European Journal of Clinical Pharmacology, 2005, Vol 61, Issue 7, p507
- ISSN
0031-6970
- Publication type
Article
- DOI
10.1007/s00228-005-0927-4