The Weight of Pharmacokinetic Parameters for Mycophenolic Acid in Prediction of Rejection Outcome: The Receiver Operating Characteristic Curve Analysis

Pawiński, Tomasz; Durlik, M.; Szlaska, Iwona; Urbanowicz, A.; Ostrowska, Joanna; Gralak, Beata; Majchrzak, Jadwiga

doi:10.1016/j.transproceed.2005.11.084

Cited by 13 publications

(9 citation statements)

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“…It is now well-established that CSA decreases MPA exposure by inhibiting the enterohepatic recirculation of the drug (13,14), and although we are unaware of any additional effects of antiretroviral medications on MMF pharmacokinetics, it may be that adequate MPA exposure is particularly critical in preventing AR in HIVϩ recipients, especially given the frequent presence of other high-risk factors, such as AA ethnicity. Moreover, the absence of clear support in the literature for a substantial clinical benefit of therapeutic drug monitoring of MPA (15), along with the demonstration that MPA trough values are more variable and less predictive for the risk of AR than is the area under the curve and that predose concentrations poorly correlate with area under the curve (15)(16)(17)(18)(19)(20), still do not negate the possibility that monitoring of MPA levels played a contributory role in preventing AR in our patients. Along these lines, several investigators have established trough level cutoffs below which the incidence of AR was felt to be significantly increased in adult renal transplant recipients on CSA in the early posttransplant period, ranging from 0.8 to 1.3 mg/L (17)(18)(19)21).…”

Section: Compared Outcomes In 38mentioning

confidence: 58%

“…Moreover, the absence of clear support in the literature for a substantial clinical benefit of therapeutic drug monitoring of MPA (15), along with the demonstration that MPA trough values are more variable and less predictive for the risk of AR than is the area under the curve and that predose concentrations poorly correlate with area under the curve (15)(16)(17)(18)(19)(20), still do not negate the possibility that monitoring of MPA levels played a contributory role in preventing AR in our patients. Along these lines, several investigators have established trough level cutoffs below which the incidence of AR was felt to be significantly increased in adult renal transplant recipients on CSA in the early posttransplant period, ranging from 0.8 to 1.3 mg/L (17)(18)(19)21). Without monitoring, most of our patients (and perhaps many of those in the prior studies mentioned) would have carried MPA levels below this threshold beyond the first posttransplant month, presumably increasing their risk for AR.…”

Section: Compared Outcomes In 38mentioning

confidence: 58%

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Preliminary Experience With Renal Transplantation in HIV+ Recipients: Low Acute Rejection and Infection Rates

et al. 2008

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Our findings suggest that HIV+ patients on highly active antiretroviral therapy can undergo successful renal transplantation with a low incidence of both AR and AIDS-associated and non-AIDS associated infections, despite associated risk factors for poorer outcome. Our encouraging but preliminary results with this protocol will need to be verified in larger numbers of HIV+ renal allograft recipients with longer follow-up.

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Section: Compared Outcomes In 38mentioning

confidence: 58%

Section: Compared Outcomes In 38mentioning

confidence: 58%

Preliminary Experience With Renal Transplantation in HIV+ Recipients: Low Acute Rejection and Infection Rates

et al. 2008

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“…Many retrospective studies found significant relationships between MPA AUC 0-12 h and BPAR or side effects in various types of populations [31][32][33][34][35], but the few prospective studies lead to diverging conclusions. The FDCC study found no statistically significant differences in outcome between the fixed-dose group and the dose-adjusted group [14], whereas the Apomygre trial did [13].…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in type I and II inosine monophosphate dehydrogenase genes and association with clinical outcome in patients on mycophenolate mofetil

Gensburger¹,

Schaik

Picard³

et al. 2010

Pharmacogenetics and Genomics

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“…Previous studies have demonstrated that MPA AUC may predict the risk of acute rejection and toxicity; however, single‐point sampling at particular trough levels has shown poor correlation with the risk of acute rejection and toxicity . The wide variability and clear concentration–effect relationship are thought to be the most compelling arguments favouring therapeutic drug monitoring (TDM) for MPA, and individualization of MMF dose using TDM based on the MPA AUC .…”

Section: Introductionmentioning

confidence: 99%

Systematic external evaluation of published population pharmacokinetic models of mycophenolate mofetil in adult kidney transplant recipients co‐administered with tacrolimus

Zhang

Sheng

Liu

et al. 2019

Brit J Clinical Pharma

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AIMSVarious mycophenolate mofetil (MMF) population pharmacokinetic (popPK) models have been developed to describe its PK characteristics and facilitate its optimal dosing in adult kidney transplant recipients co-administered with tacrolimus. However, the external predictive performance has been unclear. Thus, this study aimed to comprehensively evaluate the external predictability of published MMF popPK models in such populations and investigate the potential influencing factors. METHODSThe external predictability of qualified popPK models was evaluated using an independent dataset. The evaluation included prediction-and simulation-based diagnostics, and Bayesian forecasting. In addition, factors influencing model predictability, especially the impact of structural models, were investigated. RESULTSFifty full PK profiles from 45 patients were included in the evaluation dataset and 11 published popPK models were identified and evaluated. In prediction-based diagnostics, the prediction error within ±30% was less than 50% in most published models. The prediction-and variability-corrected visual predictive check and posterior predictive check showed large discrepancies between British Journal of Clinical Pharmacology Br J Clin Pharmacol (2019) 85 746-761 746 the observations and simulations in most models. Moreover, the normalized prediction distribution errors of all models did not follow a normal distribution. Bayesian forecasting demonstrated an improvement in the model predictability. Furthermore, the predictive performance of two-compartment (2CMT) models incorporating the enterohepatic circulation (EHC) process was not superior to that of conventional 2CMT models. CONCLUSIONSThe published models showed large variability and unsatisfactory predictive performance, which indicated that therapeutic drug monitoring was necessary for MMF clinical application. Further studies incorporating potential covariates need to be conducted to investigate the key factors influencing model predictability of MMF. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Population pharmacokinetic analyses are widely used to describe mycophenolate mofetil pharmacokinetic characteristics in adult kidney transplant recipients co-administered with tacrolimus and facilitate dose individualization. • Model transferability can be influenced by centre-related factors, and it is unclear whether these models can be appropriately extrapolated to other centres. WHAT THIS STUDY ADDS• We comprehensively evaluated the external predictability of published models using an independent dataset.• The published models performed unsatisfactorily in prediction-and simulation-based diagnostics.• The investigation of the impact of model structure did not show that incorporating the EHC process could improve predictive performance. External evaluation of MMF popPK models Br J Clin Pharmacol (2019) 85 746-761 747 External evaluation of MMF popPK models Br J Clin Pharmacol (2019) 85 746-761 749 External evaluation of MMF popPK models Br J Clin Pharmacol (2019) 85 746-761 759

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The Weight of Pharmacokinetic Parameters for Mycophenolic Acid in Prediction of Rejection Outcome: The Receiver Operating Characteristic Curve Analysis

Cited by 13 publications

References 13 publications

Preliminary Experience With Renal Transplantation in HIV+ Recipients: Low Acute Rejection and Infection Rates

Preliminary Experience With Renal Transplantation in HIV+ Recipients: Low Acute Rejection and Infection Rates

Polymorphisms in type I and II inosine monophosphate dehydrogenase genes and association with clinical outcome in patients on mycophenolate mofetil

Systematic external evaluation of published population pharmacokinetic models of mycophenolate mofetil in adult kidney transplant recipients co‐administered with tacrolimus

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