Comparison Of Pharmacokinetics And Gastrointestinal Symptoms Among Different Formulations Of Mycophenolate Applied To Recipients After Renal Transplantation On Early Period

Objective: To investigate the pharmacokinetics and gastrointestinal side-effects of three mycophenolate formulations applied to early recipients after kidney transplantation.Methods: 130 renal transplant recipients who underwent kidney transplantation at the Organ Transplantation Division of Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology from January of 2016 to October of 2018 were selected as subjects and divided according to three dosage forms of mycophenolic acid drugs.130 patients were respectively administrated with enteric-coated mycophenolate sodium tablet(60 cases),mycophenolate mofetil capsules(27 cases)and mycophenolate mofetil dispersible tablets(43 cases)within 24 hours after surgery.On the 7th day after surgery,multiple plasma samples were taken after the morning dose during a 12 hour dosing interval(before dosing and 0.5,1,1.5,2,3,4,6,8,10,and 12 hours after administration).Predose concentrations(C0),maximum plasma concentration(Cmax),time to Cmax(Tmax),and area under the concentration-time curve(AUC0-12h),as well as gastrointestinal adverse events were compared within 1 week after surgery.Results: All of three dosage forms of MPA drugs show large between-and within-subject pharmacokinetic variability.In terms of curve stability,mycophenolate mofetil capsules is superior to the other two.The Tmax values of the drugs were(1.65�1.51)h(MMF),(2.52�2.19)h(MPA-DT),and(3.7�2.35)h(EC-MPS),respectively.P=0.000 was considered significant among the three individual groups.The difference between MMF group and EC-MPS group was statistically significant(P=0.000),and also the difference between MPA-DT group and EC-MPS group was statistically significant(P=0.004).There was no significant difference in peak time between MMF group and MPA-DT group(P=0.153).There was no statistically significant difference among the three dosage forms of MPA-C0,MPA-Cmax,MPA-AUC0-12 h,and gastrointestinal side effects within 7 days after operation(P>0.05).The gastrointestinal symptoms of all of three dosage forms of MPA drugs were mainly abdominal distension,diarrhea and reflux.Conclusion: In the early stage after kidney transplantation,all of three mycophenolate formulations display greater within-patient variability.In terms of the stability of the concentration-time curve,MMF is more stable than EC-MPS and MPA-DT.Thus,routine monitoring should be performed after kidney transplantation to facilitate dosing adjustment.In the early postoperative period after kidney transplantation,it is not recommended to estimate the area under the concentration-time curve of patients by the limited sampling strategy.There were no statistically significant differences among three formulations of mycophenolate in the MPA plasma concentration and the short-term efficacy.It was safe and effective.