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Pharmacokinetic-pharmacodynamic modeling of metoprolol stereoisomers in spontaneously hypertensive rat

  
@article{APS6546,
	author = {Xiao-Xing Yin and Yin-Di Zhang and Jian-Ping Luo and Xiao-Ping Huang and Jian-Ping Shen and Yong Ding and Da-Kuang Huang},
	title = {Pharmacokinetic-pharmacodynamic modeling of metoprolol stereoisomers in spontaneously hypertensive rat},
	journal = {Acta Pharmacologica Sinica},
	volume = {18},
	number = {2},
	year = {2016},
	keywords = {},
	abstract = {AIM: 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.
CONCLUSION: Stereo-selective drug distribution and different potencies of the
inhibitory effects of (+)-Met and (-)-Met existed in SHR.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/6546}
}