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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2004, Vol. 9 ›› Issue (8): 868-871.

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Study on quantitative structures-pharmacokinetic relationship of dipyridines calcium ion antagonists

LIU You-Ping1, 2, SONG Nai-Ning1, 3, LIU Chang-Xiao1   

  1. 1National Key Laboratory of Pharmacokinetics and Pharmacodynamics, Tianjin Institute of Pharmaceutical Research,Tianjin 300193, China;
    2Laboratory of Drug Metablism and Pharmacokinetics, Shenyang Pharmaceutical University,Shenyang 110016, Liaoning, China;
    3Department of Pharmacology, Tianjin Medical University, Tianjin 300070, China
  • Received:2004-04-16 Revised:2004-06-30 Online:2004-08-26 Published:2020-11-20

Abstract: AIM: To study on the quantitative structures-pharmacokinetic relationship of dipyridines calcium ion antagonists to provide the theoretic method to screen new drugs in early period.METHODS: The structures of calcium ion antagonists were conversed from two to three dimensional structure by Insight Ⅱ Program. The conversed structures were optimized to the minimum energy by the steepest descent and conjugate gradient methods. The physico-chemical parameters of the optimized structures, including Log P, surface area, volume, hydration energy, refractivity and polarizability, were calculated by HyperChem Program.The interrelation between structures and pharmacokinetic parameters for calcium ionantagonists was analyzed.RESULTS: There was a good correlation between the hydrophobicity constants (Log P) and the reached peak time (Tmax) after extravenous administration of the calcium ion antagonists to the subjects. The correlation coefficient was over 0.9.CONCLUSION: The correlation between the chemical structure and its pharmacokinetic parameters can provide instructions to new drug design for calcium ion antagonists.

Key words: dipyridines, calcium ion antagonists, molecular mechanics and dynamics, pharmacokinetic parameters

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