#2047 Trough-level guided dosing is reliable for mycophenolate mofetil but not for enteric-coated mycophenolic sodium

Abstract Background and Aims While trough level (TL) guided dosing is usus for calcineurin inhibitors, mycophenolic acid (MPA) was marketed as a one-size-fits-all drug. TL has been reported to be a poor surrogate marker of MPA exposure by reason of complex pharmacokinetics. Measurement of area under the curve (AUC) remains the gold-standard for MPA dosing. Method We measured MPA TL and AUC in 299 KTRs at the University Hospital of Zurich. KTRs with agreement between TL and AUC target range of 40-60 mg/Lxh were compared to KTRs with missing agreement between TL and AUC for differences regarding baseline characteristics and co-medication. Results For mycophenolate mofetil (MMF, n = 218) a high correlation between TL and AUC was observed, p < 0.0001, r = 0.85, while correlation was only low for enteric-coated mycophenolate sodium (EC-MPS, n = 81), p = 0.002, r = 0.34, Fig. 1. However, a high correlation between MPA level 4 hours after EC-MPS intake (C4L) and AUC was found, p < 0.0001, r = 0.94. ROC analysis defined an MMF-TL range of >2.05 mg/l (sensitivity 68%, specificity 89%) and <3.05 mg/l (sensitivity 70%, specificity 81%) correlating with an AUC of 40-60 mg/Lxh. Lack of proton pump inhibitors (PPI) use was significantly associated with incorrect classification (n = 71/218). For EC-MPS C4L a range of >1.25 mg/l (sensitivity 98, specificity 100) and <4.4 mg/l (sensitivity 93, specificity 91) was defined for an AUC of 40-60 mg/Lxh. Here, non-tacrolimus-based immunosuppression was significantly associated with incorrect classification (n = 7/81). Conclusion MMF dosing according to TL highly correlates with AUC especially in KTRs treated with PPI. In contrast, EC-MPS dosing according to C4L is preferred especially in context of tacrolimus-based immunosuppression.