Abstract
Background: Hypertension is a common acute presentation that requires effective medication for control. Few comparative effectiveness trials exist to guide which agents offer the most efficient response. Our objective was to perform a design simulation to determine if a future study comparing the effect of intravenous (IV) nicardipine or labetalol was warranted.
Methods: We created a predictive model using known clinical responses to currently recommended dosing of nicardipine and labetalol. For nicardipine, we used a three-compartment, weight-normalized pharmacokinetic nonlinear mixed-effects model. For labetalol, BP and HR changes were modeled as a function of time, group (pretreated or untreated within 24 hours), and total dose. Clinically relevant BP and HR changes were defined as >15% and >20% of baseline, respectively. At least 500 patients were simulated and results compared to known clinical data.
Results: Our models demonstrated that the rate of clinically relevant blood pressure drop within 30 minutes of initiation in the nicardipine group would be 61% versus 14-19%, without with a >20% HR decrease, for labetalol.
Conclusions: BP and HR models of antihypertensives can be designed to predict the published data reasonably well. In this fashion the need for comparative effectiveness trials can be assessed.
W. Frank Peacock, Earvin Liang, Long Kwei, Robert J. Korsan, Michelle L. Green, Bill Poland, Meina T. Tang, Joseph Varon
