Pharmacokinetics and Bioavailability of Mycophenolic Acid After Intravenous Administration and Oral Administration of Mycophenolate Mofetil to Heart Transplant Recipients

Armstrong, Victor W.; Shipkova, Maria; Tenderich, Gero; Parsa, Amin; Schröder, Heike; Oellerich, Michael

doi:10.1097/00007890-200407271-01229

Cited by 9 publications

(10 citation statements)

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“…The oral bioavailability of MPA after MMF administration is reported to be 80.7 to 94% (Bullingham et al, 1998;Pescovitz et al, 2000;Staatz and Tett 2007), such that MMF is essentially completely hydrolyzed to MPA by esterases (Bullingham et al, 1998). Because MMF was almost completely absent in plasma from patients with renal transplants (Bullingham et al, 1996;Armstrong et al, 2005), the conversion from MMF to the active form MPA is considered to occur rapidly in the blood, intestine, and liver, after gastrointestinal absorption (Lee et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Involvement of Carboxylesterase 1 and 2 in the Hydrolysis of Mycophenolate Mofetil

Fujiyama¹,

Miura²,

Kato³

et al. 2010

Drug Metab Dispos

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ABSTRACT:Mycophenolate mofetil (MMF) is the ester prodrug of the immunosuppressant agent mycophenolic acid (MPA) and is rapidly activated by esterases after oral administration. However, the role of isoenzymes in MMF hydrolysis remains unclear. Although human plasma, erythrocytes, and whole blood contain MMF hydrolytic activities, the mean half-lives of MMF in vitro were 15.1, 1.58, and 3.20 h, respectively. Thus, blood esterases seemed to contribute little to the rapid MMF disappearance in vivo. In vitro analyses showed that human intestinal microsomes exposed to 5

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Section: Introductionmentioning

confidence: 99%

Involvement of Carboxylesterase 1 and 2 in the Hydrolysis of Mycophenolate Mofetil

Fujiyama¹,

Miura²,

Kato³

et al. 2010

Drug Metab Dispos

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“…Mycophenolate mofetil administration, MMF undergoes near complete pre-systemic metabolism to MPA by widely distributed esterases [12]. Two studies [10,13] have demonstrated MMF plasma concentrations below the limit of assay detection at all times following oral administration. According to manufacturer information, gastrointestinal absorption of EC-MPS is 93% and bioavailability is 72% [5].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Monitoring of Mycophenolate in Transplantation: Is It Justified?

Barraclough¹,

Staatz²,

Isbel³

et al. 2009

CDM

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Mycophenolate mofetil (MMF) is the preferred antimetabolite in solid organ transplantation. It is a prodrug that undergoes pre-systemic metabolism to mycophenolic acid (MPA), the active drug moiety. MMF is typically administered as a fixed dose without routine monitoring of MPA concentrations. However, a role for therapeutic drug monitoring (TDM) of MPA has been suggested based on the drug's narrow therapeutic window and considerable between-subject variability. Dose-normalized MPA area under the concentration-time curve (AUC) has been observed to vary >/=10-fold. Some of this variability may be accounted for by patient variability in renal and liver function, serum albumin and haemoglobin levels, body mass, concomitant medication exposure and genetic polymorphisms in enzymes responsible for drug metabolism and transport, but much is unexplained. Widespread adoption of MPA TDM has been limited by the impracticality of full 0 to 12 hour AUC measurement (AUC(0-12)), poor correlation between pre-dose MPA concentration and AUC(0-12), ongoing questions regarding the utility of free versus total MPA measurements and lack of evidence correlating MPA exposure with clinical outcomes. Two recent randomized studies evaluating the role of MPA TDM in renal transplant recipients have reported conflicting results. Promising areas of ongoing study include use of Bayesian forecasting to predict MPA dosage and measurement of inosine monophosphate dehydrogenase activity. This review provides an overview of the pharmacokinetics of MMF in solid organ transplantation, and discusses the benefits and limitations of MPA monitoring. Areas that require additional research are identified.

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“…After ingestion, MMF is rapidly hydrolyzed to the active metabolite mycophenolic acid (MPA) (2,3). MPA is glucuronidated (4) in the liver, kidney, and gastrointestinal tract to the inactive MPA 7-O-glucuronide (MPAG), mainly by UDP-glucuronosyltransferase 1A9 (UGT1A9), but also by other enzymes of the UGT1A superfamily (5)(6)(7)(8).…”

mentioning

confidence: 99%

Multidrug Resistance Protein 2 Genetic Polymorphisms Influence Mycophenolic Acid Exposure in Renal Allograft Recipients

Verbeke²,

2006

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Pharmacokinetics and Bioavailability of Mycophenolic Acid After Intravenous Administration and Oral Administration of Mycophenolate Mofetil to Heart Transplant Recipients

Cited by 9 publications

References 0 publications

Involvement of Carboxylesterase 1 and 2 in the Hydrolysis of Mycophenolate Mofetil

Involvement of Carboxylesterase 1 and 2 in the Hydrolysis of Mycophenolate Mofetil

Therapeutic Monitoring of Mycophenolate in Transplantation: Is It Justified?

Multidrug Resistance Protein 2 Genetic Polymorphisms Influence Mycophenolic Acid Exposure in Renal Allograft Recipients

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