Population pharmacokinetics and bioavailability of tacrolimus in kidney transplant patients
- 10 April 2007
- journal article
- research article
- Published by Wiley in British Journal of Clinical Pharmacology
- Vol. 64 (6), 750-7
- https://doi.org/10.1111/j.1365-2125.2007.02895.x
Abstract
The use of tacrolimus is complicated by its narrow therapeutic index and wide intra- and interpatient variability. Tacrolimus population pharmacokinetics, including bioavailability, were investigated in an adult kidney transplant cohort to identify patient characteristics that influence pharmacokinetics. The database (drug monitoring data) included 83 adult kidney transplant recipients and analysis was performed by a population approach with NONMEM. Data were collected during the first months after transplantation. Patients were administered oral or intravenous tacrolimus as part of a triple immunosuppressive regimen that also included mycophenolate mofetil and corticosteroids. Subsequent doses were adjusted on the basis of clinical evidence of efficacy and toxicity as in routine therapeutic drug monitoring. A one compartment open model with linear absorption and elimination adequately described the data. The typical value of minimal clearance was 1.8 +/- 0.2 l h(-1). Clearance increased with time post transplantation to reach 50% of maximal value after 3.8 +/- 0.5 days, with a maximal value of 5.6 l h(-1). Moreover clearance increased by approximately 1.6 fold (range 0.5-1.6) if the dose of prednisone was >25 mg. The typical value for volume of distribution, V, (98 +/- 13 l kg(-1)) was similar to reported values in kidney transplant patients. The oral bioavailability of tacrolimus was poor and ranged from 11.2 to 19.1%. No covariates significantly influenced V or F. The number of days postoperation and corticosteroid dose were significant covariates influencing tacrolimus clearance.This publication has 27 references indexed in Scilit:
- Toward better outcomes with tacrolimus therapy: Population pharmacokinetics and individualized dosage prediction in adult liver transplantationLiver Transplantation, 2003
- Low tacrolimus concentrations and increased risk of early acute rejection in adult renal transplantationNephrology Dialysis Transplantation, 2001
- THE EFFECT OF GUT METABOLISM ON TACROLIMUS BIOAVAILABILITY IN RENALTRANSPLANT RECIPIENTS1,2Transplantation, 2001
- Influence of posttransplant time on dose and concentration of tacrolimus in liver transplant patientsTransplant International, 1998
- Human Cytochrome P450 Enzymes: A Status Report Summarizing Their Reactions, Substrates, Inducers, and InhibitorsDrug Metabolism Reviews, 1997
- RELATIONSHIP OF FK506 WHOLE BLOOD CONCENTRATIONS AND EFFICACY AND TOXICITY AFTER LIVER AND KIDNEY TRANSPLANTATIONTransplantation, 1996
- Analysis of Tacrolimus (FK 506) in Relation to Therapeutic Drug MonitoringTherapeutic Drug Monitoring, 1995
- Clinical Pharmacokinetics of TacrolimusClinical Pharmacokinetics, 1995
- Pharmacokinetics of FK506 After Intravenous and Oral Administration in Patients Awaiting Renal TransplantationThe Journal of Clinical Pharmacology, 1994
- FK506 TROUGH LEVELS IN WHOLE BLOOD AND PLASMA IN LIVER TRANSPLANT RECIPIENTSTransplantation, 1994