Population pharmacokinetics of mycophenolic acid during the first week after renal transplantation.

https://arctichealth.org/en/permalink/ahliterature173599
Source
Eur J Clin Pharmacol. 2005 Aug;61(7):507-16
Publication Type
Article
Date
Aug-2005
Author
Christine E Staatz
Stephen B Duffull
Bryce Kiberd
Albert D Fraser
Susan E Tett
Author Affiliation
School of Pharmacy, University of Queensland, Brisbane, QLD, 4072, Australia. chris@pharmacy.uq.edu.au
Source
Eur J Clin Pharmacol. 2005 Aug;61(7):507-16
Date
Aug-2005
Language
English
Publication Type
Article
Keywords
Adult
Aged
Female
Humans
Immunosuppressive Agents - pharmacokinetics
Kidney Transplantation
Male
Middle Aged
Mycophenolic Acid - pharmacokinetics
Nova Scotia
Population Surveillance
Abstract
To investigate the population pharmacokinetics of mycophenolic acid (MPA) in adult kidney transplant recipients during the crucial first week after transplantation.
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 NONMEM. 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 boot strapped samples from the original data. Bias and precision were determined through comparison of observed and predicted concentrations.
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 l/h (5%) and apparent volume of the central compartment of 65 l (7%). CL/F decreased significantly with increasing serum albumin (1.42 l/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 boot strapped and final model parameter estimates (all differences
PubMed ID
16049701 View in PubMed
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