Pharmacokinetic-pharmacodynamic modeling of metoprolol stereoisomers in spontaneously hypertensive rat
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.
Keywords:
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.