title: Synergistic effects of clopidogrel and fufang danshen dripping pills by modulation of the metabolism target and pharmacokinetics.
abstract: Background and Objective. The aim was to evaluate the synergistic effects of clopidogrel and FDDP by modulating the metabolism target and the pharmacokinetics. Methods. The inhibition effect of FDDP on the CES1 was first investigated by the molecular simulation method, and the synergistic effects on the pharmacokinetics of CPGS were studied as follows: SD rats were treated with oral clopidogrel alone at a dosage of 30 mg/kg or the combination of clopidogrel and FDDP at dosages of 30 mg/kg and 324 mg/kg, respectively, for 21 days. The concentrations of CPGS in the blood plasma samples were determined and the calculated concentrations were used to determine the pharmacokinetic parameters. Results. 20 compounds in FDDP potentially interacted with CES1 target. The CPGS showed a two-compartment model pharmacokinetic profile. The concentration-time course of CPGS was not changed by FDDP, but FDDP decreased the peak plasma concentration and area under the curve of CPGS. Conclusion. The CES1's activity could be partly inhibited by FDDP through the molecular simulation investigation. The concentration-time course of CPGS was altered slightly by FDDP. The results demonstrated the synergistic effects of clopidogrel and FDDP by modulating both the pharmacokinetics and the target metabolism.
authors.affiliation: College of Pharmacy, Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, China ; Food and Drug College, Anhui Science and Technology University, Fengyang, Anhui, China ; Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, No. 155 Hanzhong Road, Baixia District, Nanjing, Jiangsu 210029, China.
authors.forename: Shitang
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, No. 155 Hanzhong Road, Baixia District, Nanjing, Jiangsu 210029, China.
authors.forename: Wenzheng
authors.initials: W
authors.lastname: Ju
authors.affiliation: Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, No. 155 Hanzhong Road, Baixia District, Nanjing, Jiangsu 210029, China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Dai
authors.affiliation: College of Pharmacy, Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, China.
authors.forename: Wenzhu
authors.initials: W
authors.lastname: Zhao
authors.affiliation: College of Pharmacy, Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, China.
authors.forename: Xiaogui
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Cardiology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, China.
authors.forename: Zhuyuan
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Clinical Pharmacology, General Hospital of Nanjing Military Area Command, Nanjing, China.
authors.forename: Hengshan
authors.initials: H
authors.lastname: Tan
authors.affiliation: Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, No. 155 Hanzhong Road, Baixia District, Nanjing, Jiangsu 210029, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Wang