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OBJECTIVE To study the combined pharmacokinetic-pharmacodynamic (PK-PD) model of metoprolol stereoisomers, and compare their inhibitory effects on cardiovascular system in the spontaneously hypertensive rats (SHR). METHODS The drug concentration in plasma was measured by the reversed phase HPLC and the drug effects were recorded by polygraph. The pharmacokinetic parameters and the PK-PD model parameters were calculated. RESULTS The plasma concentration-time profiles were adequately described by two-compartment model. Differences of Vd between (+)-Met and (-)-Met were found. The relationships between effects and concentration of effect compartment were represented by the sigmoid-Emax model. The Css50 of Vmax, dp/dtmax, and HR inhibitory effects of (+)-Met were larger than those of (-)-Met. CONCLUSIONS Stereo-selective drug distribution and different potencies of the inhibitory effects of (+)-Met and (-)-Met existed in SHR.
X X Yin, and
Y D Zhang, and
J P Luo, and
X P Huang, and
J P Shen, and
Y Ding, and
D K Huang
July 2006,
Naunyn-Schmiedeberg's archives of pharmacology,
X X Yin, and
Y D Zhang, and
J P Luo, and
X P Huang, and
J P Shen, and
Y Ding, and
D K Huang
January 2007,
Journal of pharmacological and toxicological methods,
X X Yin, and
Y D Zhang, and
J P Luo, and
X P Huang, and
J P Shen, and
Y Ding, and
D K Huang
May 2007,
Acta pharmacologica Sinica,
X X Yin, and
Y D Zhang, and
J P Luo, and
X P Huang, and
J P Shen, and
Y Ding, and
D K Huang
May 2017,
Naunyn-Schmiedeberg's archives of pharmacology,
X X Yin, and
Y D Zhang, and
J P Luo, and
X P Huang, and
J P Shen, and
Y Ding, and
D K Huang
December 1976,
Clinical science and molecular medicine. Supplement,
X X Yin, and
Y D Zhang, and
J P Luo, and
X P Huang, and
J P Shen, and
Y Ding, and
D K Huang
March 2007,
Clinical and experimental pharmacology & physiology,
X X Yin, and
Y D Zhang, and
J P Luo, and
X P Huang, and
J P Shen, and
Y Ding, and
D K Huang
January 2000,
Archives of medical research,
X X Yin, and
Y D Zhang, and
J P Luo, and
X P Huang, and
J P Shen, and
Y Ding, and
D K Huang
January 2012,
Critical reviews in biomedical engineering,
X X Yin, and
Y D Zhang, and
J P Luo, and
X P Huang, and
J P Shen, and
Y Ding, and
D K Huang
January 1996,
Methods and findings in experimental and clinical pharmacology,
X X Yin, and
Y D Zhang, and
J P Luo, and
X P Huang, and
J P Shen, and
Y Ding, and
D K Huang
May 2005,
Journal of pain and symptom management,
