Evaluation of Multiple Linear Regression Limited Sampling Strategies for Enteric-Coated Mycophenolate Sodium in Adult Kidney Transplant Recipients
1Pharmacy, University of Queensland, Brisbane, QLD, Australia
2Department of Nephrology, Princess Alexandra Hospital, Brisbane, QLD, Australia
3Department of Pathology, The Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
Meeting: 2018 American Transplant Congress
Abstract number: C99
Keywords: Area-under-curve (AUC), Immunosuppression
Session Information
Session Name: Poster Session C: Kidney Immunosuppression: Novel Regimens and Drug Minimization
Session Type: Poster Session
Date: Monday, June 4, 2018
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall 4EF
Background: Although multiple linear regression-based limited sampling strategies (LSS) have been published for enteric-coated mycophenolate sodium none have been evaluated for prediction of subsequent mycophenolic acid (MPA) exposure. This study aimed to examine the predictive performance of published LSS for estimation of future MPA area under the concentration-time curve from 0-12 hours (AUC0-12) in renal transplant recipients.
Methods: Total MPA plasma concentrations were measured in twenty adult renal transplant patients on two occasions a week apart. Subjects were approximately one-month post-transplant and receiving concomitant tacrolimus. Samples were taken at 0, 0.33, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4 and 8 hours and 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on the first and second sampling occasion, respectively. Predicted MPA AUC0-12 were calculated using nineteen published LSS and data from the first or second sampling occasion for each patient, and compared to the second occasion full MPA AUC0-12 calculated using the linear trapezoidal rule. Bias (median percentage prediction error [MPPE]) and imprecision (median absolute prediction error [MAPE]) were determined.
Results: MPPE and MAPE for prediction of full MPA AUC0-12 were <15% for four LSS, using the data from the same (second) occasion. One equation (1.583C1 + 0.765C2 + 0.369C2.5 + 0.748C3 + 1.518C4 + 2.158C6 +3.292C8 + 3.6690) achieved bias and imprecision <15% for prediction of a future MPA AUC0-12, where the predicted AUC0-12 from the first occasion was compared to the full AUC0-12 from the second. All LSS with acceptable predictive performance included concentrations taken at least 6 hours after the dose.
Conclusions: Only one LSS had acceptable bias and precision for future estimation. Accurate dosage prediction using a multiple linear regression-based LSS was not possible without concentrations at least 6 hours after the dose.
CITATION INFORMATION: Staatz C., Brooks E., Isbel N., McWhinney B., Tett S. Evaluation of Multiple Linear Regression Limited Sampling Strategies for Enteric-Coated Mycophenolate Sodium in Adult Kidney Transplant Recipients Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Staatz C, Brooks E, Isbel N, McWhinney B, Tett S. Evaluation of Multiple Linear Regression Limited Sampling Strategies for Enteric-Coated Mycophenolate Sodium in Adult Kidney Transplant Recipients [abstract]. https://atcmeetingabstracts.com/abstract/evaluation-of-multiple-linear-regression-limited-sampling-strategies-for-enteric-coated-mycophenolate-sodium-in-adult-kidney-transplant-recipients/. Accessed May 12, 2025.« Back to 2018 American Transplant Congress