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Factors determining the response to calcium antagonists in hypertension
R Donnelly1, J L Reid, P A Meredith
1University Department of Materia Medica, Stobhill Hospital, Glasgow, Scotland.
Insights
Individual responses to calcium channel blockers like nifedipine and verapamil vary significantly. This study used a kinetic-dynamic model to show that patient blood pressure response to these antihypertensives can be predicted and potentially optimized.
Area of Science:
- Pharmacology
- Cardiovascular Medicine
- Clinical Pharmacy
Background:
- Interindividual variability in antihypertensive response to calcium antagonists is significant.
- Pharmacokinetic and pharmacodynamic factors contribute to this variability.
- Understanding individual responses is crucial for effective hypertension management.
Purpose of the Study:
- To characterize acute and chronic antihypertensive responses to nifedipine and verapamil in individual patients.
- To evaluate the relationship between pretreatment blood pressure and drug responsiveness.
- To explore the utility of an integrated kinetic-dynamic model for optimizing calcium antagonist therapy.
Main Methods:
- Utilized an integrated kinetic-dynamic model to analyze data from 28 hypertensive patients (14 on nifedipine, 14 on verapamil).
- Measured blood pressure response (fall in mmHg) per unit drug concentration.
- Assessed both acute (first dose) and chronic (4-6 weeks) responses.
Main Results:
- Nifedipine showed higher responsiveness (-0.48 to -0.49 mmHg/ng/ml) compared to verapamil (-0.13 to -0.12 mmHg/ng/ml).
- Initial drug responsiveness strongly correlated with pretreatment blood pressure and long-term responsiveness (p < 0.001).
- Individualized concentration-effect parameters were derived.
Conclusions:
- Integrated kinetic-dynamic modeling provides a basis for understanding and optimizing individual patient responses to calcium antagonists.
- The findings highlight the potential for personalized drug therapy in hypertension.
- Responsiveness to nifedipine and verapamil is patient-specific and influenced by baseline blood pressure.
Abstract:
Pharmacokinetic and pharmacodynamic variability account for the large interindividual differences in the antihypertensive response to treatment with a calcium antagonist. Using an integrated kinetic-dynamic model, the acute and chronic (4-6 weeks) responses to nifedipine (n = 14) and verapamil (n = 14) were characterized for individual hypertensive patients in terms of fall in blood pressure per unit drug concentration. The responsiveness to nifedipine, as the mean of the group, was -0.48 mm Hg/ng/ml following the first dose and -0.49 mm Hg/ng/ml after chronic dosing. The corresponding values for verapamil were -0.13 and -0.12 mm Hg/ng/ml, respectively. For nifedipine and verapamil, the responsiveness to the first dose was significantly correlated both with the height of the pretreatment blood pressure (p less than 0.001) and the responsiveness after 4-6 weeks of treatment (p less than 0.001). Parameters derived from an individual approach to concentration-effect analysis are useful for evaluating the determinants of response to calcium antagonists and form a potential basis for optimizing drug therapy in individual patients.