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Population pharmacokinetics of tacrolimus in adult kidney transplant recipients.
Clin Pharmacol Ther. 2002 Dec; 72(6):660-9.CP

Abstract

OBJECTIVES

The aims of this study were to investigate the population pharmacokinetics of tacrolimus in adult kidney transplant recipients and to identify factors that explain variability.

METHODS

Population analysis was performed on retrospective data from 70 patients who received oral tacrolimus twice daily. Morning blood trough concentrations were measured by liquid chromatography-tandem mass spectrometry. Maximum likelihood estimates were sought for apparent clearance (CL/F) and apparent volume of distribution (V/F), with the use of NONMEM (GloboMax LLC, Hanover, Md). Factors screened for influence on these parameters were weight, age, gender, postoperative day, days of tacrolimus therapy, liver function tests, creatinine clearance, hematocrit fraction, corticosteroid dose, and potential interacting drugs.

RESULTS

CL/F was greater in patients with abnormally low hematocrit fraction (data from 21 patients only), and it decreased with increasing days of therapy and AST concentrations (P <.01). Average parameter estimates were as follows: CL/F = 31.8 L/h (hematocrit <0.33), CL/F = 24.2 L/h (hematocrit >0.33), and V/F = 2080 L. Marked interindividual variability (42% to 111%) and residual random error (3.7 ng/mL) were observed. On the basis of the derived model, a patient with normal AST (20 U/L) or high AST (200 U/L) concentrations 7 days after commencement of therapy would require a tacrolimus dose of 4.6 mg or 4.0 mg, respectively, to achieve a steady-state trough concentration of 10 ng/mL.

CONCLUSIONS

The population pharmacokinetics of tacrolimus in adult kidney transplant recipients showed wide variability. Thus it is not possible to use a standard tacrolimus dose as an empiric predictor of concentration in this population. An understanding of factors that influence the pharmacokinetics of tacrolimus may assist in drug dosage decisions.

Authors+Show Affiliations

School of Pharmacy, University of Queensland, Brisbane, Australia. c.staatz@pharmacy.uq.edu.auNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Validation Study

Language

eng

PubMed ID

12496747

Citation

Staatz, Christine E., et al. "Population Pharmacokinetics of Tacrolimus in Adult Kidney Transplant Recipients." Clinical Pharmacology and Therapeutics, vol. 72, no. 6, 2002, pp. 660-9.
Staatz CE, Willis C, Taylor PJ, et al. Population pharmacokinetics of tacrolimus in adult kidney transplant recipients. Clin Pharmacol Ther. 2002;72(6):660-9.
Staatz, C. E., Willis, C., Taylor, P. J., & Tett, S. E. (2002). Population pharmacokinetics of tacrolimus in adult kidney transplant recipients. Clinical Pharmacology and Therapeutics, 72(6), 660-9.
Staatz CE, et al. Population Pharmacokinetics of Tacrolimus in Adult Kidney Transplant Recipients. Clin Pharmacol Ther. 2002;72(6):660-9. PubMed PMID: 12496747.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Population pharmacokinetics of tacrolimus in adult kidney transplant recipients. AU - Staatz,Christine E, AU - Willis,Charlene, AU - Taylor,Paul J, AU - Tett,Susan E, PY - 2002/12/24/pubmed PY - 2003/1/22/medline PY - 2002/12/24/entrez SP - 660 EP - 9 JF - Clinical pharmacology and therapeutics JO - Clin Pharmacol Ther VL - 72 IS - 6 N2 - OBJECTIVES: The aims of this study were to investigate the population pharmacokinetics of tacrolimus in adult kidney transplant recipients and to identify factors that explain variability. METHODS: Population analysis was performed on retrospective data from 70 patients who received oral tacrolimus twice daily. Morning blood trough concentrations were measured by liquid chromatography-tandem mass spectrometry. Maximum likelihood estimates were sought for apparent clearance (CL/F) and apparent volume of distribution (V/F), with the use of NONMEM (GloboMax LLC, Hanover, Md). Factors screened for influence on these parameters were weight, age, gender, postoperative day, days of tacrolimus therapy, liver function tests, creatinine clearance, hematocrit fraction, corticosteroid dose, and potential interacting drugs. RESULTS: CL/F was greater in patients with abnormally low hematocrit fraction (data from 21 patients only), and it decreased with increasing days of therapy and AST concentrations (P <.01). Average parameter estimates were as follows: CL/F = 31.8 L/h (hematocrit <0.33), CL/F = 24.2 L/h (hematocrit >0.33), and V/F = 2080 L. Marked interindividual variability (42% to 111%) and residual random error (3.7 ng/mL) were observed. On the basis of the derived model, a patient with normal AST (20 U/L) or high AST (200 U/L) concentrations 7 days after commencement of therapy would require a tacrolimus dose of 4.6 mg or 4.0 mg, respectively, to achieve a steady-state trough concentration of 10 ng/mL. CONCLUSIONS: The population pharmacokinetics of tacrolimus in adult kidney transplant recipients showed wide variability. Thus it is not possible to use a standard tacrolimus dose as an empiric predictor of concentration in this population. An understanding of factors that influence the pharmacokinetics of tacrolimus may assist in drug dosage decisions. SN - 0009-9236 UR - https://www.unboundmedicine.com/medline/citation/12496747/Population_pharmacokinetics_of_tacrolimus_in_adult_kidney_transplant_recipients_ L2 - https://doi.org/10.1067/mcp.2002.129304 DB - PRIME DP - Unbound Medicine ER -