Concentration/Effect Analysis of Antihypertensive Drugs

Area of Science:

• Pharmacology
• Cardiovascular Medicine
• Clinical Pharmacy

Background:

• Antihypertensive agents, including calcium antagonists and alpha(1)-blockers, exhibit a concentration-effect relationship.
• Variability in study designs and methodologies complicates the analysis and comparison of these relationships.

Purpose of the Study:

• To review and analyze the concentration/effect relationship of antihypertensive agents.
• To evaluate different methodologies used in concentration/effect studies.
• To assess the applicability of these findings for drug development and hypertension treatment.

Main Methods:

• Review of existing studies on antihypertensive agents.
• Analysis of concentration/effect data using linear and E(max) models.
• Evaluation of pharmacokinetic/pharmacodynamic (PK/PD) modeling and blood pressure measurement techniques.

Main Results:

• A close correlation exists between plasma concentrations of antihypertensives and blood pressure reduction.
• Methodological heterogeneity (linear vs. E(max) models, PK/PD modeling, placebo correction, blood pressure measurement) prevents definitive conclusions.
• Significant inter-subject variability in responsiveness limits the utility of derived threshold levels.

Conclusions:

• A more integrated protocol is needed for future concentration/effect studies in antihypertensive drug development.
• Individualized dose adjustment based on concentration/effect analysis is effective after single-dose administration.
• This approach is currently inadequate for the conventional, long-term treatment of hypertension.