Mycophenolate Pharmacokinetics And Association With Response To Acute Graft vs Host Disease (GVHD) Treatment

Jacobson, Pamala A.; Juang, Jyuhn Huarng; Wu, Juan; Kim, M.; Logan, Brent R.; Alousi, Amin M.; Grimley, Michael; Bolaños-Meade, Javier; Ho, Vincent T.; Levine, John E.; Weisdorf, Daniel J.

doi:10.1016/j.bbmt.2009.12.430

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“…Combination regimens that include MMF have shown that it permits a reduction in dose of cyclosporine, tacrolimus, or corticosteroid without increasing the chances of acute rejections [7][8][9] . The systemic exposure of MPA is unpredictable and wide variations in pharmacokinetics have been reported 2,[10][11][12][13] . Thus, therapeutic drug monitoring (TDM) of MMF is routinely practiced in solid organ transplants to target a specified area under the concentration-time curve (AUC) based on exposure-effect relationship.…”

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confidence: 99%

A Limited Sampling Strategy for Therapeutic Drug Monitoring of Mycophenolate Mofetil for Prophylaxis of Acute Graft-Versus-Host Disease in Allogeneic Stem Cell Transplantation

et al. 2020

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A universally accepted strategy for therapeutic drug monitoring (TDM) of mycophenolate mofetil (MMF) in the prevention of acute graft-versus-host disease (aGVHD) in allogenic hematopoietic stem cell transplantation (alloHSCT) does not exist. We explored the feasibility of developing a limited sampling strategy (LSS) for TDM of MMF in this setting. Patients undergoing alloHSCT received standard MMF-cyclosporine prophylaxis, with MMF administered twice daily (BD) for matched transplant recipients or thrice daily (TID) in haploidentical transplantation. Intensive blood sampling was carried out on day 7 and area under the concentration–time curve (AUC) of mycophenolic acid (MPA), the active metabolite, was estimated using noncompartmental analysis. The ability of MPA exposure defined by AUC0-12 to discriminate between responders (patients who did not develop GVHD) and nonresponders (patients who developed GVHD) was determined by receiver operating characteristic curve analysis. Patients were divided into training and validation sets within BD and TID groups. Mathematical equations were developed from the training set to predict AUC0-12 from an abbreviated AUC involving a limited number of sampling points. The equations were validated in the validation set by comparing the MPA AUC0-12 predicted from LSS with the observed AUC0-12. It was observed that patients with AUC0-12 ≤18.99 mg*h/L had a higher risk of developing aGVHD [odds ratio (OR) = 2.63 (1.17 to 5.87), P = 0.06]. The benefit was more in matched transplant recipients [OR = 3.5 (1.30 to 9.49), P = 0.05] as compared to haploindentical transplant [OR = 2.8 (0.49 to 15.91), P = NS]. Using the mathematical equations, the observed AUC0-12 was predicted with 92.31% accuracy in the BD subset and 100% accuracy in the TID subset for a combined accuracy of 94.76%. A set of just three samples that constituted the abbreviated AUC1-4 was used to develop the predictive models. The LSS could be employed for the therapeutic monitoring of MMF particularly in patients undergoing matched hematopoietic stem cell transplantation.

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