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Population pharmacokinetics and Bayesian estimation of cyclosporine in a Tunisian population of hematopoietic stem cell transplant recipient
- Source :
- European Journal of Clinical Pharmacology. 68:1517-1524
- Publication Year :
- 2012
- Publisher :
- Springer Science and Business Media LLC, 2012.
-
Abstract
- Therapeutic drug monitoring of cyclosporine minimizes the risk of toxicity and acute rejection after transplantation. Areas under the curve (AUCs) rather than trough concentration-based monitoring are recommended. Population pharmacokinetics (PopPK) modeling and Bayesian estimation seem to be the best way to predict cyclosporine disposition and dose requirements to achieve the therapeutic target in an individual patient because of the possibility of predicting cyclosporine AUC using only a few blood samples. Our objectives were to build a PopPk model for cyclosporine in a Tunisian population of HSCT patients and to develop a Bayesian method for the estimation of individual cyclosporine AUC. The PopPk of cyclosporine was studied using nonlinear mixed effects modeling (NONMEM) in 30 patients (index group) receiving cyclosporine on a twice-daily basis. Ten blood samples were collected after steady-state morning cyclosporine dose. Bayesian estimation of individual AUC was made on the basis of three blood concentration measurements in an independent group of 30 patients (test group). A two-compartment model with first-order absorption and a lag time provided the best fitting. The population mean estimate and interindividual variability from the final model for CL, Ka, Tlag, V1, V2, and Q were 25.4 L/h (CV = 38.72 %), 0.214 h−1(CV = 28.5 %), 0.382 h, 10.9 L (85.73 %), 496 L, and 5 L/h, respectively. Covariates had no discernible effects on cyclosporine pharmacokinetics in our population. Bayesian estimation provided an accurate estimation of AUC, although a bias was observed leading to slight underprediction of AUC (bias −1.03 %). A very satisfactory precision was observed (RMSE 12.07 %). We report a PopPK model for cyclosporine in Tunisian HSCT patients. Bayesian estimation using only three concentrations provides good prediction of cyclosporine exposure. These tools allow us to routinely estimate cyclosporine AUC in a clinical setting.
- Subjects :
- Adult
Male
medicine.medical_specialty
Tunisia
Adolescent
Metabolic Clearance Rate
medicine.medical_treatment
Population
Urology
Graft vs Host Disease
Hematopoietic stem cell transplantation
Pharmacology
Models, Biological
Intestinal absorption
Young Adult
Bayes' theorem
Pharmacokinetics
medicine
Humans
Pharmacology (medical)
Child
education
education.field_of_study
medicine.diagnostic_test
business.industry
Hematopoietic Stem Cell Transplantation
Reproducibility of Results
Bayes Theorem
General Medicine
Middle Aged
NONMEM
Transplantation
Intestinal Absorption
Therapeutic drug monitoring
Cyclosporine
Female
Drug Monitoring
business
Immunosuppressive Agents
Half-Life
Subjects
Details
- ISSN :
- 14321041 and 00316970
- Volume :
- 68
- Database :
- OpenAIRE
- Journal :
- European Journal of Clinical Pharmacology
- Accession number :
- edsair.doi.dedup.....d33b6de77cc75ed25ef7ccc789eb6d91