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Aim:To investigate the pharmacokinetic (PK) and the pharmacodynamic (PD)properties of telmisartan in spontaneously hypertensive (SH) rats using an indi-rect response and effect-compartment link models,and compare two PK-PD mod-els fitting quality.Methods:The SH rats received a single oral dose of 2,4,and 8mg/kg of telmisartan.The plasma concentrations of telmisartan were determinedby the liquid chromatography-mass spectrum method.The mean arterial bloodpressure was measured to characterize the pharmacodynamics of telmisartan bytail-cuff manometry.The relationship for the telmisartan concentration-hypoten-sive effect in the SH rats was characterized using an indirect response model.Results:The PK parameters showed dose proportionality,with a long terminalhalf-life of 16 h,a clearance of 0.15 L.kg~(-1)·h~(-1),and a volume of distribution of 5.36L·kg~(-1)in the study.For the indirect response PD model,the estimated K_(in) were 36.6,34.1,and 32.8%·h~(-1),K_(out) were 36.7,34.6,and 31.9·h~(-1);the IC_(50)values were 86.2,95.8,and 91.1 ng·mL~(-1);and the area under the effect curve (AUEC) were 762.8,1490.5,and 2086.2 mmHg·h at three doses,respectively.For the effect-compart-ment model,the K_(eo) were 29.4,33.8,and 28.7·h~(-1);the IC_(50)values were 78.2,85.7,and80.9 ng·mL~(-1),and the AUEC were 781.5,1602.8,and 2215.7 mmHg·h at three doses,respectively.Conclusion:According to Akaike’s information criterion values,theproposed indirect response model provided a more appropriate and good-fittingPK/PD characterization of telmisartan than the effect-compartment link model inSH rats.
Aim: To investigate the pharmacokinetic (PK) and the pharmacodynamic (PD) properties of telmisartan in spontaneously hypertensive (SH) rats using an indi-rect response and effect-compartment link models, and compare two PK-PD mod- els fitting quality. Methods: The SH rats received a single oral dose of 2,4, and 8 mg / kg of telmisartan. The plasma concentrations of telmisartan were determined by the liquid chromatography-mass spectrum method. The mean arterial blood pressure was measured to characterize the phantomodynamics of telmisartan bytail -cuff manometry.The relationship for the telmisartan concentration-hypoten-sive effect in the SH rats was characterized using an indirect response model. Results: The PK parameters showed dose proportionality, with a long terminal life-life of 16 h, a clearance of 0.15 L. kg -1 h -1 and a volume of distribution of 5.36 L kg -1 in the study. For the indirect response PD model, the estimated K in 36.6 , 34.1, and 32.8% · h ~ (-1), 36.7, 34.6, and 31.9 the IC 50 values were 86.2, 95.8, and 91.1 ng · mL -1; and the area under the effect curve (AUEC) were 762.8, 1490.5, and 2086.2 mmHg · h at three doses, respectively. for the effect-compartmental model, K_ (eo) were 29.4, 33.8, and 28.7 · h -1; IC 50 values were 78.2, 85.7, and 80.9 ng · mL ~ (-1), and the AUEC were 781.5, 1602.8, and 2215.7 mmHg · h at three doses, respectively. Conlusion: According to Akaike’s information criterion value, theproposed indirect response model provided a more appropriate and good-fittingPK / PD characterization of telmisartan than the effect-compartment link model in SH rats.