Relationships between plasma drug level and inhibitory effect
| Model | In Vivo Assessment of AngII Blockade | ||
|---|---|---|---|
| Tasosartan 100 mg p.o.1-a | Tasosartan 50 mg i.v.1-a | Enoltasosartan 2.5 mg i.v. | |
| Log/linear | r = 0.662 | r = 0.617 | r = 0.050 |
| E= A + B·log(C) | P < .0001 | P = .0002 | P > .5 |
| E max = 67.8 ± 7.5% | E max = 69.5 ± 9.1% | E max = 44.1 ± 6.5% | |
| Hill sigmoid | EC50 = 12.0 ± 7.7 ng/ml | EC50 = 11.0 ± 6.7 ng/ml | EC50 = 18.3 ± 47.5 ng/ml |
| χ2 = 0.0928 | χ2 = 0.0803 | χ2 = 0.498 | |
| In Vitro Assessment of AngII Blockade | |||
|---|---|---|---|
| Log/linear | r = 0.938 | r = 0.957 | r = 0.214 |
| E= A + B·log(C) | P < .0001 | P < .0001 | P = .143 |
| E max = 88.6 ± 3.4% | E max = 86.2 ± 5.1% | E max = 46.3 ± 4.6% | |
| Hill sigmoid | EC50 = 9.2 ± 2.1 ng/ml | EC50 = 11.1 ± 3.0 ng/ml | EC50 = 48.3 ± 20.5 ng/ml |
| χ2 = 0.0199 | χ2 = 0.0029 | χ2 = 0.0167 | |
E, effect expressed in percentage inhibition (respectively AngII response in vivo and 125I-AngII in vitro binding displaced in the RRA); C, plasma concentration of drug (ng/ml). In log/linear model, A and B, respectively, represent the intercept and the slope of the constructed regression line, and r is the correlation coefficient of this line. In the Hill sigmoid model, Emaxrepresents the theoretical maximal inhibition; EC50 = concentration of drug at 50% of EC50.
↵1-a Restricted to the first 8 h of the time-course profiles.