[Pharmacokinetic model for the enterohepatic circulation of mycophenolic acid].
OBJECTIVE
To develop a pharmacokinetic model for the enterohepatic circulation of mycophenolic acid (MPA).


METHODS
Twenty healthy volunteers were orally given a single dose of 500 mg mycophenolate mofetil. Plasma samples were collected during 48 hours and MPA concentration was measured by HPLC method. Pharmacokinetic (PK) model was established based on physiological and biopharmaceutical consideration and PK parameters were obtained using nonlinear mixed effect model.


RESULTS
The proposed model included an intestinal compartment and gall bladder compartment in addition to the central compartment. The predicted time-concentration curve and AUC0-t, Cmax, Tmax estimated by the established model were in agreement with the observations.


CONCLUSIONS
The established model was well defined for the MPA disposition and could afford a useful approach for the further clinical investigation.
Jiao
Zheng
Z
Clinical Pharmacy Laboratory, Huashan Hospital, Fudan University, Shanghai, China. jiaozhen@online.sh.cn
Shen
Jie
J
Zhong
Long-jin
LJ
Yu
Yun-qiu
YQ
Zhong
Ming-kang
MK
D000328:Adult; D019540:Area Under Curve; D004764:Enterohepatic Circulation / Q000502:physiology*; D020719:Glucuronides / Q000493:pharmacokinetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*
D020719:Glucuronides; D007166:Immunosuppressive Agents; C113145:mycophenolic acid glucuronide; D009173:Mycophenolic Acid