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Concentration-effect relationships and implications for trough-to-peak ratio
1University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow, Scotland.
American Journal of Hypertension
|October 1, 1996
Summary
The trough-to-peak ratio of antihypertensive drugs can be dose-dependent, particularly with sigmoid-Emax concentration-effect relationships. Linear relationships ensure dose-independent ratios and longer duration of action for better antihypertensive effects.
Area of Science:
- Pharmacology
- Clinical Pharmacy
Background:
- Trough-to-peak ratio (TPR) is an index for antihypertensive drug duration of action.
- Guidelines aim to prevent inappropriate dosing to extend apparent drug action.
- TPR may exhibit dose-dependency in certain scenarios.
Purpose of the Study:
- To analyze the contribution of concentration-effect relationships to TPR dose-dependency.
- To compare antihypertensive drug duration of action based on concentration-effect models.
Main Methods:
- Examination of the underlying concentration-antihypertensive effect relationship.
- Analysis of dose-dependency of TPR based on linearity or sigmoid-Emax models.
Main Results:
- Linear concentration-effect relationships result in dose-independent TPR.
- Sigmoid-Emax concentration-effect relationships typically lead to dose-dependent TPR.
- Linear drugs demonstrate superior duration of action compared to Emax drugs.
Conclusions:
- The nature of the concentration-effect relationship is critical for TPR dose-dependency.
- Linear drugs offer greater persistence of antihypertensive effect beyond the dosage interval.
- Understanding these relationships optimizes antihypertensive drug selection and dosing.