Concentration-effect relationships were characterized in individual hypertensive patients treated with single and multiple doses of ketanserin. There were significant changes in the concentration-effect parameters during continued treatment, and overall there was a reduction in antihypertensive responsiveness, from -0.47 to -0.25 mmHg/ng per ml. The nature of the changes, however, raises the possibility that there were associated changes in the site and mechanism of the underlying antihypertensive action. It is possible that a peripheral mechanism, perhaps alpha 1-adrenoceptor antagonism, is relatively more pronounced after the first dose whereas a central mechanism, perhaps related to serotonergic antagonism, is relatively more important during chronic treatment. We conclude that this technique of concentration-effect analysis may be useful in exploring mechanisms of action and identifying issues which require further clarification.
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