Determination of mycophenolate area under the curve by limited sampling strategy

Yeung, S; Tong, Kwok Lung; Tsang, Wing Pui; Tang, Hongying; Fung, Samuel; Chan, HH; Chan, Angus C.W.; Chan, Laurence

doi:10.1016/s0041-1345(00)02326-5

Cited by 42 publications

(21 citation statements)

References 7 publications

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“…This issue needs to be resolved. Limited sampling strategies for AUC monitoring of mycophenolate have shown varying agreement with full 12-to 14-point AUC measurements of total MPA (85)(86)(87)(88)(89)(90). Table 2 summarizes some limited sampling strategies that have been proposed.…”

Section: Will the Results Of The Drug Assay Make A Significant Differmentioning

confidence: 99%

Mycophenolate Mofetil for Solid Organ Transplantation: Does the Evidence Support the Need for Clinical Pharmacokinetic Monitoring?

Cox

Ensom²

2003

Therapeutic Drug Monitoring

111

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The need for clinical pharmacokinetic monitoring (CPM) of the immunosuppressant mycophenolate mofetil (MMF) has been debated. Using a previously developed algorithm, the authors reviewed the evidence to support or refute the utility of CPM of MMF. First, MMF has proven efficacy for prevention of organ rejection in renal and cardiac transplant populations. In addition, the pharmacologically active form of MMF, mycophenolic acid (MPA), can be measured readily in plasma, and relationships between the incidence of rejection and MPA predose concentrations and MPA area under the curve (AUC) have been reported. A lower limit of the therapeutic range (MPA predose concentrations >1.55 microg/mL, as measured by enzyme multiplied immunoassay technique [EMIT], or MPA AUC >30 or 40 microg. h/mL, as measured by high-performance liquid chromatography [HPLC]) has been suggested to prevent rejection in renal allograft patients. Similarly, in cardiac transplant patients, decreased incidences of organ rejection have been reported in patients with MPA concentrations >2 or 3 microg/mL (using EMIT) and total AUC values >42.8 microg. h/mL (using HPLC). However, the relationship between pharmacokinetic parameters and adverse events in renal and cardiac transplant patients remains unclear. Due to the nature of antirejection therapy, the pharmacologic response of MMF is not readily assessable, and therapy is life-long. MPA pharmacokinetics exhibit large inter- and intrapatient variability and may be altered in specific patient populations due to changes in protein binding, concomitant disease states, or interactions with concurrent immunosuppressants. Therefore, on the basis of current evidence, CPM can provide more information regarding efficacy of MMF than clinical judgment alone in select patient populations. However, further randomized, prospective trials are required to clarify unresolved issues. Specifically, an upper limit of the therapeutic range, above which the risk of side effects is increased, needs to be elucidated for MMF therapy. Other future directions for research include determining a practical limited sampling strategy for MPA AUC; clarifying the relationship between free MPA concentrations, efficacy, and toxicity; and defining the pharmacodynamic relationship between activity of inosine monophosphate dehydrogenase (the enzyme inhibited by MPA) and risk of rejection or adverse effects.

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Section: Will the Results Of The Drug Assay Make A Significant Differmentioning

confidence: 99%

Mycophenolate Mofetil for Solid Organ Transplantation: Does the Evidence Support the Need for Clinical Pharmacokinetic Monitoring?

Cox

Ensom²

2003

Therapeutic Drug Monitoring

111

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“…The target C2 level in the first 2 months is 1700-2100 ng/mL. A 12-h MPA AUC (AUC [0][1][2][3][4][5][6][7][8][9][10][11][12] …”

Section: Pharmacokinetic Analysis and Laboratory Methodsmentioning

confidence: 99%

Early Adequate Mycophenolic Acid Exposure is Associated with Less Rejection in Kidney Transplantation

Kiberd¹,

Lawen²,

Fraser³

et al. 2004

American Journal of Transplantation

126

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“…The other minor, yet important metabolite of MPA is mycophenolic acid acyl glucuronide (AcMPAG, Fig. 1), which could inhibit IMPDH in vitro in a concentration-dependent manner (Yeung et al, 2001). Whether it has EHC is still undetermined and needs further research in order to solidify its involvement.…”

Section: Introductionmentioning

confidence: 99%

simultaneous determination of mycophenolic acid and its metabolites by HPLC and pharmacokinetic studies in rat plasma and bile

Gao

Peng

et al. 2011

Arch. Pharm. Res.

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In this study, we determined the pharmacokinetics of mycophenolic acid (MPA) and its metabolites mycophenolic acid glucuronide (MPAG) and acyl glucuronide (AcMPAG) in rat plasma and bile, using a newly developed HPLC method. Protein precipitation and liquid-liquid extraction were employed in sample preparation of plasma and bile, respectively. The HPLC methods included a gradient elution consisting of acetonitrile and phosphate buffer at a flow rate of 1.2 mL/min, with UV detection at 254 nm. The HPLC method was found to be sensitive and linear (r(2) ≥ 0.9991, 1.0-128.0 and 0.25-32.0 mg/L for MPA; 1.0-128.0 and 0.5-64.0 mg/L for MPAG; 0.25-32.0 and 1.0-128.0 mg/L for AcMPAG in rat plasma and bile, respectively), precise (both the intra- and inter-day variability were ≤ 6.8%), and accurate (both the intra- and inter-day accuracy were between 92.2% and 105.4%). The average extraction efficiencies for MPA, MPAG and AcMPAG were 85.3%, 100.1%, and 94.7% in plasma, and 88.0%, 67.3%, and 68.3% in bile, respectively. The method was successfully employed for pharmacokinetic studies in plasma and bile after oral administration of mycophenolate mofetil (prodrug of MPA) in rats.

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Determination of mycophenolate area under the curve by limited sampling strategy

Cited by 42 publications

References 7 publications

Mycophenolate Mofetil for Solid Organ Transplantation: Does the Evidence Support the Need for Clinical Pharmacokinetic Monitoring?

Mycophenolate Mofetil for Solid Organ Transplantation: Does the Evidence Support the Need for Clinical Pharmacokinetic Monitoring?

Early Adequate Mycophenolic Acid Exposure is Associated with Less Rejection in Kidney Transplantation

simultaneous determination of mycophenolic acid and its metabolites by HPLC and pharmacokinetic studies in rat plasma and bile

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