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Population pharmacokinetic estimation of tacrolimus apparent clearance in adult liver transplant recipients.
Ther Drug Monit. 2005 Aug; 27(4):422-30.TD

Abstract

The goal was to study the factors affecting tacrolimus apparent clearance (CL/F) in adult liver transplant recipients. Tacrolimus dose and concentration data (n = 694) were obtained from 67 liver transplant recipients (22 female and 45 male), and the data were analyzed using a nonlinear mixed-effect modeling (NONMEM) method. A 1-compartment pharmacokinetic model with first-order elimination, an absorption rate constant fixed at 4.5 hours, and first-order conditional estimation was used to describe tacrolimus disposition. The predictive performance of the final model was evaluated using data splitting and assessing bias and precision of the estimates. The population estimate of tacrolimus CL/F and apparent volume of distribution (V/F) were found to be 21.3 L/h (95% confidence interval, CI, 18.0-24.6 L/h) and 316.1 L (95% CI 133-495 L), respectively. Neither patient's age, weight, gender, nor markers of liver function influenced tacrolimus CL/F. The final model was TVCL = 21.3 + 9.8 x (1 - HEM) + 3.4 x (1 - ALB) - 2.1 x (1 - DIL) - 7.4 x (1 - FLU), where TVCL, typical estimate of apparent clearance, HEM = 0 if hematocrit <35%, otherwise 1; ALB = 0 if albumin <3.5 g/dL, otherwise 1; DIL = 0 if diltiazem is coadministered, otherwise 1; FLU = 0 if fluconazole is coadministered, otherwise 1. This study identified the factors that significantly affect tacrolimus disposition in adult liver transplant recipients during the early posttransplantation period. This information will be helpful to clinicians for dose individualization of tacrolimus in liver transplant recipients with different clinical conditions including anemia or hypoalbuminemia or in those patients receiving diltiazem or fluconazole.

Authors+Show Affiliations

Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island 02881, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

16044097

Citation

Zahir, Hamim, et al. "Population Pharmacokinetic Estimation of Tacrolimus Apparent Clearance in Adult Liver Transplant Recipients." Therapeutic Drug Monitoring, vol. 27, no. 4, 2005, pp. 422-30.
Zahir H, McLachlan AJ, Nelson A, et al. Population pharmacokinetic estimation of tacrolimus apparent clearance in adult liver transplant recipients. Ther Drug Monit. 2005;27(4):422-30.
Zahir, H., McLachlan, A. J., Nelson, A., McCaughan, G., Gleeson, M., & Akhlaghi, F. (2005). Population pharmacokinetic estimation of tacrolimus apparent clearance in adult liver transplant recipients. Therapeutic Drug Monitoring, 27(4), 422-30.
Zahir H, et al. Population Pharmacokinetic Estimation of Tacrolimus Apparent Clearance in Adult Liver Transplant Recipients. Ther Drug Monit. 2005;27(4):422-30. PubMed PMID: 16044097.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Population pharmacokinetic estimation of tacrolimus apparent clearance in adult liver transplant recipients. AU - Zahir,Hamim, AU - McLachlan,Andrew J, AU - Nelson,Ameeta, AU - McCaughan,Geof, AU - Gleeson,Margaret, AU - Akhlaghi,Fatemeh, PY - 2005/7/27/pubmed PY - 2006/4/28/medline PY - 2005/7/27/entrez SP - 422 EP - 30 JF - Therapeutic drug monitoring JO - Ther Drug Monit VL - 27 IS - 4 N2 - The goal was to study the factors affecting tacrolimus apparent clearance (CL/F) in adult liver transplant recipients. Tacrolimus dose and concentration data (n = 694) were obtained from 67 liver transplant recipients (22 female and 45 male), and the data were analyzed using a nonlinear mixed-effect modeling (NONMEM) method. A 1-compartment pharmacokinetic model with first-order elimination, an absorption rate constant fixed at 4.5 hours, and first-order conditional estimation was used to describe tacrolimus disposition. The predictive performance of the final model was evaluated using data splitting and assessing bias and precision of the estimates. The population estimate of tacrolimus CL/F and apparent volume of distribution (V/F) were found to be 21.3 L/h (95% confidence interval, CI, 18.0-24.6 L/h) and 316.1 L (95% CI 133-495 L), respectively. Neither patient's age, weight, gender, nor markers of liver function influenced tacrolimus CL/F. The final model was TVCL = 21.3 + 9.8 x (1 - HEM) + 3.4 x (1 - ALB) - 2.1 x (1 - DIL) - 7.4 x (1 - FLU), where TVCL, typical estimate of apparent clearance, HEM = 0 if hematocrit <35%, otherwise 1; ALB = 0 if albumin <3.5 g/dL, otherwise 1; DIL = 0 if diltiazem is coadministered, otherwise 1; FLU = 0 if fluconazole is coadministered, otherwise 1. This study identified the factors that significantly affect tacrolimus disposition in adult liver transplant recipients during the early posttransplantation period. This information will be helpful to clinicians for dose individualization of tacrolimus in liver transplant recipients with different clinical conditions including anemia or hypoalbuminemia or in those patients receiving diltiazem or fluconazole. SN - 0163-4356 UR - https://www.unboundmedicine.com/medline/citation/16044097/Population_pharmacokinetic_estimation_of_tacrolimus_apparent_clearance_in_adult_liver_transplant_recipients_ L2 - https://doi.org/10.1097/01.ftd.0000170029.36573.a0 DB - PRIME DP - Unbound Medicine ER -