Wing L M
Department of Clinical Pharmacology, Flinders Medical Centre, Bedford Park, Adelaide, Australia.
J Hypertens Suppl. 1994 Nov;12(8):S85-90.
EFFECT OF ELIMINATION HALF-LIFE ON TROUGH:PEAK RATIO IN BETA-BLOCKERS: Maximal beta-adrenoceptor blockade and peak blood pressure reduction are achieved with plasma concentrations that are below the peak postdose concentrations observed when therapeutic doses are given. As a result, any trough:peak variation in the blood pressure response is likely to depend on the proportion of the dose interval during which maximal beta-blockade is maintained, and on the relationship between the elimination half-life of the drug, the dose and the dose interval. Acceptable trough:peak ratios (> 70%) for the blood pressure response to beta-blockade with a single daily dose are usually found with drugs that have an elimination half-life of over 6 h or when slow-release preparations are used for drugs with a shorter half-life. OTHER FACTORS THAT INFLUENCE THE TROUGH:PEAK RATIO: The interpretation of trough:peak ratios when beta-blockers are used may be complicated by circadian variations in the blood pressure response, with low blood pressure levels during sleep and an early morning rise upon waking. The blood pressure response-time relationships for beta-blockers with vasodilator properties appear to be similar to those for 'plain' beta-blockers, although there may be greater attenuation of the rise in blood pressure upon waking when multiple-action agents are used. Furthermore, the blood pressure of elderly patients with systolic hypertension may show an attenuated response to beta-blockers, resulting in a less favourable trough:peak ratio.
It is not clear whether blood pressure 'responders' to beta-blockers have a pattern of response that is different from the mean of a heterogeneous group. Further studies with appropriate designs are required to clarify these issues.
消除半衰期对β受体阻滞剂谷峰比的影响：给予治疗剂量时，血浆浓度低于给药后峰值浓度即可实现最大β肾上腺素能受体阻滞和最大血压降低。因此，血压反应中的任何谷峰变化可能取决于维持最大β受体阻滞的给药间隔比例，以及药物消除半衰期、剂量和给药间隔之间的关系。对于每日单次给药的β受体阻滞血压反应，当药物消除半衰期超过6小时，或半衰期较短的药物使用缓释制剂时，通常可获得可接受的谷峰比（>70%）。影响谷峰比的其他因素：使用β受体阻滞剂时，谷峰比的解释可能会因血压反应的昼夜变化而复杂化，睡眠期间血压水平较低，醒来时血压会在清晨升高。具有血管舒张特性的β受体阻滞剂的血压反应时间关系似乎与“普通”β受体阻滞剂相似，尽管使用多作用药物时，醒来时血压升高的衰减可能更大。此外，老年收缩期高血压患者的血压对β受体阻滞剂的反应可能减弱，导致谷峰比不太理想。
尚不清楚对β受体阻滞剂有血压“反应”的患者是否具有与异质性群体平均值不同的反应模式。需要进行适当设计的进一步研究来阐明这些问题。
