Integration of genetic and clinical data to analyze pharmaco | 16880
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International Research Journal of Pharmacy and Pharmacology

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Integration of genetic and clinical data to analyze pharmacokinetic profile of mycophenolic acid in a population of Chinese patients with glomerular disease


Qian Xiang, Feng Yu, Ji-cheng LV, Xia Zhao, Jing Han, Ying Zhou, Si-qian Du, Ming-hui Zhao, Hong Zhang, Yi-min Cui1 and Hai-yan Wang.

We measured the free and plasma concentrations of total Mycophenolic acid (MPA) after single and multiple oral doses of Mycophenolate mofetil (MMF) in 24 glomerular disease patients with different renal function. Clinical characteristics and genetic polymorphisms of UGTs, MRP2, MDR1 and OATP8 were further investigated. After a single oral dose, those patients carrying the MDR1 3435CC allele had a 40.81% higher mean AUC0-24 of total MPA compared to MDR1 3435T carriers, and the difference was more significant in patients with anestimated glomerular filtration rate (eGFR) less than 60mL/min/1.73m2. After repeat doses, MDR1 C3435T genotype in coordination with the MRP2C-24T allele elevated the total MPA level, and serum albumin level were positively correlated with free MPA exposure.Furthermore, there were strong negative correlations between eGFR and AUC6–12/AUC0–12for both free and total MPA. In conclusion, these factors should be evaluated to keep drug safety and guide proper therapy of MMF in patient with glomerular diseases.

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