A limited sampling strategy for the simultaneous estimation of tacrolimus, mycophenolic acid and unbound prednisolone exposure in adult kidney transplant recipients

• Published in: Nephrology (Carlton, Vic.) Vol. 17; no. 3; pp. 294 - 299
• Main Authors: BARRACLOUGH, KATHERINE A, ISBEL, NICOLE M, JOHNSON, DAVID W, HAWLEY, CARMEL M, LEE, KATIE J, MCWHINNEY, BRETT C, UNGERER, JACOBUS P, CAMPBELL, SCOTT B, LEARY, DIANA R, STAATZ, CHRISTINE E
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Publishing Asia 01.03.2012
• Subjects: Adult; Area Under Curve; area under the concentration-time curve; Drug Monitoring; Female; Humans; Immunosuppressive Agents - blood; Kidney Transplantation; limited sampling strategy; Linear Models; Male; Middle Aged; mycophenolic acid; Mycophenolic Acid - blood; prednisolone; Prednisolone - blood; tacrolimus; Tacrolimus - blood
• ISSN: 1320-5358; 1440-1797
• DOI: 10.1111/j.1440-1797.2011.01560.x

Aim:  The aim of this study was to develop a limited sampling strategy (LSS) for the simultaneous estimation of exposure to tacrolimus, mycophenolic acid and unbound prednisolone in adult kidney transplant recipients. Methods:  Tacrolimus, mycophenolic acid and unbound prednisolone area under the concentration–time curve profiles from 0 to 12 h post dose (AUC0‐12) were collected from 20 subjects. Multiple linear regression analyses were performed to develop a LSS enabling the simultaneous estimation of exposure to all three drugs. Median percentage prediction error and median absolute percentage prediction error were calculated via jackknife analysis to evaluate bias and imprecision. Results:  LSS showed superior ability to predict exposure compared with single concentration–time points. A LSS incorporating concentration measurements at 0.5 h (C0.5), 2 h (C2) and 4 h (C4) post dose displayed acceptable predictive ability for all three drugs. Conclusion:  This LSS may serve as a useful research tool for further investigation of the utility of concentration monitoring of these medications. In this study, the authors have examined the predictive performance indices for three immunosuppressive drugs (tacrolimus, mycophenolic acid and prednisolone) using limited sampling at 0.5, 2 and 4 h post dose. Measurements for all three drugs demonstrated an acceptable predictive ability, making this strategy a potentially useful tool for future research studies.