Impact of Mycophenolate Mofetil Loading on Drug Exposure in the Early Posttransplant Period

Kiberd, Bryce A.; Puthenparumpil, J.J.; Fraser, Albert D.; Tett, S. E.; Lawen, Joseph

doi:10.1016/j.transproceed.2005.03.059

Cited by 8 publications

(3 citation statements)

References 19 publications

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“…Studies by Filler et al [44] and Kiberd et al [45] have outlined biliary excretion as a nonlinear process, suggesting that with higher MMF doses MPA will undergo additional enterohepatic recycling. Consequently, there is a more pronounced inhibitory effect by ciclosporin seen at higher MMF doses.…”

Section: Effect Of Concomitant Medicationsmentioning

confidence: 99%

The Evolution of Population Pharmacokinetic Models to Describe the Enterohepatic Recycling of Mycophenolic Acid in Solid Organ Transplantation and Autoimmune Disease

Sherwin

Fukuda

Brunner

et al. 2011

Clinical Pharmacokinetics

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With the increasing use of mycophenolic acid (MPA) as an immunosuppressant in solid organ transplantation and in treating autoimmune diseases such as systemic lupus erythematosus, the need for strategies to optimize therapy with this agent has become increasingly apparent. This need is largely based on MPA’s significant between-subject and between-occasion (within-subject) pharmacokinetic variability. While there is a strong relationship between MPA exposure and effect, the relationship between drug dose, plasma concentration and exposure (area under the concentration-time curve [AUC]) is very complex and remains to be completely defined. Population pharmacokinetic models using various approaches have been proposed over the past 10 years to further evaluate the pharmacokinetic and pharmacodynamic behaviour of MPA. These models have evolved from simple one-compartment linear iterations to complex multi-compartment versions that try to include various factors, which may influence MPA’s pharmacokinetic variability, such as enterohepatic recycling and pharmacogenetic polymorphisms. There have been major advances in the understanding of the roles transport mechanisms, metabolizing and other enzymes, drug-drug interactions and pharmacogenetic polymorphisms play in MPA’s pharmacokinetic variability. Given these advances, the usefulness of empirical-based models and the limitations of nonlinear mixed-effects modelling in developing mechanism-based models need to be considered and discussed. If the goal is to individualize MPA dosing, it needs to be determined whether factors which may contribute significantly to variability can be utilized in the population pharmacokinetic models. Some pharmacokinetic models developed to date show promise in being able to describe the impact of physiological processes such as enterohepatic recycling. Most studies have historically been based on retrospective data or poorly designed studies which do not take these factors into consideration. Modelling typically has been undertaken using non-controlled therapeutic drug monitoring data, which do not have the information content to support the development of complex mechanistic models. Only a few recent modelling approaches have moved away from empiricism and have included mechanisms considered important, such as enterohepatic recycling. It is recognized that well thought-out sampling schedules allow for better evaluation of the pharmacokinetic data. It is not possible to undertake complex absorption modelling with very few samples being obtained during the absorption phase (which has often been the case). It is important to utilize robust AUC monitoring which is now being propagated in the latest consensus guideline on MPA therapeutic drug monitoring. This review aims to explore the biological factors that contribute to the clinical pharmacokinetics of MPA and how these have been introduced in the development of population pharmacokinetic models. An overview of the processes involved in the enterohepatic recycling of MPA will be provided. ...

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Section: Effect Of Concomitant Medicationsmentioning

confidence: 99%

The Evolution of Population Pharmacokinetic Models to Describe the Enterohepatic Recycling of Mycophenolic Acid in Solid Organ Transplantation and Autoimmune Disease

Sherwin

Fukuda

Brunner

et al. 2011

Clinical Pharmacokinetics

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“…However, the safety profile of this approach is unknown. In addition, tacrolimus is now the most commonly used calcineurin inhibitor in the United States and there is limited information on MMF exposure when used in combination with tacrolimus (2,10).…”

Section: Ycophenolate Mofetil (Mmf Cellceptmentioning

confidence: 99%

The CLEAR Study

Gourishankar

Houde²,

Keown³

et al. 2010

Clinical Journal of the American Society of Nephrology

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“…The data were arranged in four different groups, depending on the type of CNI with which the patient was co‐treated (CsA or Tac) and depending on time after transplantation (<6 or >6 months post‐transplant). A detailed overview of MPA exposure data from the papers included in this review can be found in Tables a , b , a , and b . Overall, the dose‐normalized MPA‐AUC 0–12 was higher in Asian than in Caucasian/AA patients and similar for Caucasian and AA patients.…”

Section: Resultsmentioning

confidence: 96%

Do Asian renal transplant patients need another mycophenolate mofetil dose compared with Caucasian or African American patients?

Shuker

Hesselink

et al. 2014

Transpl Int

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Summary Mycophenolate mofetil (MMF) is used to prevent acute rejection following solid organ transplantation in transplant centers all over the world. Patients from different ethnic backgrounds are treated with this drug, for which therapeutic drug monitoring (TDM) has not become the standard of practice in most centers. Whether or not some ethnic groups require a different MMF dose has been a topic of debate in recent years. In this review, it is shown that Asian patients, compared with Caucasian patients, with a comparable MMF dose reach higher mycophenolic acid (MPA) exposure. Also clinical experience points toward more adverse events in case of treatment with 1 g MMF bid in Asian patients, and therefore, for this ethnic group, a lower maintenance dose seems justified. In contrast, African American patients reach similar drug concentrations as Caucasians patients receiving the same MMF dose, but due to immunological reasons, they require a higher MMF dose to reach comparable acute rejection incidences. When TDM is performed, clinicians can correct the dose and compensate for interethnic differences in drug exposure. Otherwise, it is important to choose the right dose. This optimal dose is 20–46% lower in Asian transplant recipients than in Caucasian or African American patients.

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Impact of Mycophenolate Mofetil Loading on Drug Exposure in the Early Posttransplant Period

Cited by 8 publications

References 19 publications

The Evolution of Population Pharmacokinetic Models to Describe the Enterohepatic Recycling of Mycophenolic Acid in Solid Organ Transplantation and Autoimmune Disease

The Evolution of Population Pharmacokinetic Models to Describe the Enterohepatic Recycling of Mycophenolic Acid in Solid Organ Transplantation and Autoimmune Disease

The CLEAR Study

Do Asian renal transplant patients need another mycophenolate mofetil dose compared with Caucasian or African American patients?

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