Elliott H L, Meredith P A
University Department of Medicine and Therapeutics, Stobhill General Hospital, Glasgow, UK.
J Hypertens Suppl. 1990 Sep;8(4):S69-71.
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.
在接受单剂量和多剂量酮色林治疗的个体高血压患者中，对浓度-效应关系进行了表征。在持续治疗期间，浓度-效应参数发生了显著变化，总体上抗高血压反应性有所降低，从-0.47降至-0.25 mmHg/ng每毫升。然而，这些变化的性质增加了潜在抗高血压作用的部位和机制存在相关变化的可能性。有可能在首剂给药后外周机制（可能是α1-肾上腺素能受体拮抗作用）相对更显著，而在长期治疗期间中枢机制（可能与5-羟色胺能拮抗作用有关）相对更重要。我们得出结论，这种浓度-效应分析技术可能有助于探索作用机制并识别需要进一步阐明的问题。
