Sites for absorption, distribution, metabolism, enterohepatic recycling (EHC), and elimination of mycophenolic acid (MPA). Sites for absorption, distribution, metabolism, enterohepatic recycling (EHC), and elimination of mycophenolic acid (MPA). The gastrointestinal tract (G.I.), presumably the stomach and upper small intestine, is the site where mycophenolate mofetil (MMF) is spontaneously hydrolyzed to produce MPA, the active drug, which is absorbed into the circulation (together with interstitial fluid, the circulation constitutes the central compartment). From the central compartment, MPA distributes throughout the body into organs and tissues, including liver, kidney, heart, lung, and others in the peripheral compartment. The glucuronide metabolites including the primary inactive mycophenolic acid glucuronide (MPAG) and the acyl glucuronide, are produced by uridine diphosphate glucuronyltransferases (UGT) in liver, GI, tract and possibly kidney. The glucuronide metabolites produced by the liver are transported, likely via the MDR1-related protein 2 (Mrp2) transporter, into bile. After excretion into bile, MPAG is hydrolyzed back to MPA via glucuronidases shed by GI tract bacteria. MPA thus formed in the GI tract reenters the circulation, thereby completing the EHC pathway. MPAG also appears in the circulation after its production from MPA in various tissues. Elimination of MPAG from the circulation occurs via renal excretion. The inhibitory effect of cyclosporine (CsA) on MPAG transport into bile is symbolized by the ⊗ symbol. Leslie M. Shaw et al. CJASN 2007;2:1062-1072 ©2007 by American Society of Nephrology