Effect of long-term coadministration of compound glycyrrhizin tablets on the pharmacokinetics of mycophenolic acid in rats

1. Mycophenolic acid (MPA), having high-protein affinity, is an immunodepressant and the genuine-active ingredient of enteric-coated mycophenolate sodium (EC-MPS) tablet that has been widely used in combination with tacrolimus or cyclosporine to prevent acute rejection after organ transplantation. Moreover, MPA mainly experiences glucuronidation and its metabolites are partly transported by multidrug resistance-associated protein (Mrp) 2 into bile then reforms MPA via enterohepatic circulation. 2. Glycyrrhizin (GL), having high-protein affinity, is the main active ingredient of compound glycyrrhizin tablet, which is often prescribed with EC-MPS, tacrolimus or cyclosporine to prevent drug-induced hepatitis. In addition, GL can inhibit Mrp2 and selectively induce CYP3A and UGTs; and it also undergoes enterohepatic circulation. 3. After 14 days of coadministration of compound GL tablets with the capsules of EC-MPS tablets, the AUC_{0-48 h} of total and free MPA was dramatically increased, and the clearance of total and free MPA was apparently decreased. It would seem reasonable that our data appear to support further investigation of this drug-drug interactions in the clinic and more careful monitoring of drug levels as well as clinical effect and toxicity in patients receiving the combination of these two agents.