Clinical Pathology: Clinical Chemistry

• Blood samples for therapeutic drug monitoring (TDM) are usually collected before the next dose; these are called “trough levels.” Sometimes blood sampling will occur soon after drug intake, leading to higher drug levels than expected.

• Mycophenolate mofetil is a prodrug, which is rapidly hydrolyzed to its active compound, MPA. MPA can be further metabolized, and its most predominant metabolite is the glucuronide (MPAG). MPAG is excreted into urine but also into the bile. After biliary secretion and deglucuronidation, free MPA can be taken up again, thereby forming an enterohepatic cycle, which contributes significantly to circulating levels of MPA. The enterohepatic cycle also causes a second peak in the MPA serum concentration time profile. This peak, which takes place approximately 8 hours after drug intake, is observed in most, but not all, patients.

• Although many immunosuppressive drugs, such as cyclosporine, tacrolimus, everolimus, and sirolimus, are measured in whole blood, MPA is measured in serum or plasma.

• The necessity for TDM of MPA is a subject of ongoing debate. However, TDM could provide the clinician with certainty about the systemic exposure to MPA, which shows significant interpatient variability.

• Some amount of the variability in drug levels is also caused by the imprecision of the assay.

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