Article

I011: Angiotensin II levels are elevated at peak and trough with once daily dosing of valsartan

01/2000; DOI: 10.1016/S0895-7061(00)01158-4
Source: OAI

ABSTRACT Angiotensin II (Ang II) levels are increased as a function of blockade of the AT1 receptor, thus it is an important pharmacodynamic parameter in patients taking angiotensin receptor blockers (ARBs). The
purpose of this study is to determine the effects of multiple doses of valsartan, an ARB, on Ang II levels in healthy subjects.
Fourteen healthy volunteers had baseline Ang II levels drawn in the fasting state, between 6 and 8 AM. These subjects then
received valsartan 80 mg QD for 7 days. Ang II levels were again drawn on day 7 prior to valsartan dosing (trough) and 6 h
after dosing (peak). Ang II levels were determined from plasma using a highly specific monoclonal antibody after solid phase
extraction (crossreactivity with other angiotensin peptides <0.1%). Day 7 predose (trough) Ang II levels were significantly
higher than at baseline (13.8 ± 11.7 pg/ml vs 6.9 ± 2.4 pg/ml, p < 0.01). Day 7, 6 h postdose (peak) Ang II levels were significantly
higher than day 7 predose (51.2 ± 35.1 pg/ml vs 13.8 ± 11.7 pg/ml, p < 0.001) and baseline levels (51.2 ± 35.1 pg/ml vs 6.9
± 2.4 pg/ml, p < 0.001). These results show that Ang II levels remain elevated 24 h after multiple doses of valsartan 80 mg
QD in healthy subjects. This suggests that the pharmacodynamic effects of AT1 receptor blockade with valsartan persist 24 h after dosing.

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