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Abstract: PO2366

A Single Time Point Plasma Concentration of Mycophenolic Acid Predicts Enteric-Coated Mycophenolate Sodium Exposure in Thai Renal Transplant Recipients

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1800 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Tanathitipuwarat, Napatsanan, Chulalongkorn University Faculty of Medicine, Bangkok, Thailand
  • Chariyavilaskul, Pajaree, Chulalongkorn University Faculty of Medicine, Bangkok, Thailand
  • Townamchai, Natavudh, Chulalongkorn University Faculty of Medicine, Bangkok, Thailand
  • Wittayalertpanya, Supeecha, Chulalongkorn University Faculty of Medicine, Bangkok, Thailand

Group or Team Name

  • Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Chulalongkorn University
Background

Enteric-coated mycophenolate sodium (EC-MPS) is a salt form of mycophenolate widely used in renal transplantation. The area under the concentration-time curve (AUC) of an active form of EC-MPS, mycophenolic acid (MPA) of ≥30 µg.h/L is highly associated with drug efficacy. However, this technique is impractical in clinical setting. Little is known regarding metabolites' AUC.

This study determined the relationships of a single time point of plasma MPA level and the optimum MPA-AUC and assessed the cut off plasma levet of that single time point to predict AUC. The full profiles of active (7-O-MPA-glucuronide; MPAG) and inactive (acyl mycophenolic acid glucuronide; AcMPAG) metabolites, both free and total form are also measured and related to its AUC.

Methods

Twenty renal transplant recipients with EC-MPS were studied. On day 3 post transplantation, plasma samples were collected at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, and 12 hours post dose. Total and free form levels of MPA and metabolites were measured using a fully validated LC-MS/MS. Receiver operating curve (ROC) was carried out.

Results

The AUC of the MPA total form moderately correlated with a single time point plasma MPA concentration at C4 (r2 = 0.50) with the concentration cut off 2.5 µg/ml (sensitivity 87%, specificity 80%, area ROC = 0.83). The AUC of the MPA free form poorly correlated with a single time point concentration. The AUCs of total and free forms of MPAG and AcMPAG highly correlated with a single time point concentration at C6 (r2 = 0.97) and C8 (r2 = 0.95) for MPAG and C4 (r2 = 0.59) and C8 (r2 = 0.81) for AcMPAG. high variability in metabolites concentrations were observed, suggesting inter-individual variability in drug metabolizing enzyme activity.

Conclusion

At the early stage post transplantation, in renal transplant recipients who received EC-MPS, a single time point of the total form plasma MPA concentration is best monitored at 4 hours post dose. The MPA level of 2.5 µg/ml at that time point predicts optimum AUC. Further studies required for the use of metabolites’ AUCs to assess drug efficacy and to evaluate a single time point concentration that predicts drug exposure.

Funding

  • Government Support - Non-U.S.