Choosing the right dose for beta-blocker treatment of hypertension: experience with tertatolol.
The determination of the optimum dosage for antihypertensive therapy, i.e. the unit dose and the administration frequency, remains one of the least discussed subjects. For beta-blockers as well as for other drugs, this determination is mainly based on the dose-effectiveness curve, the top of which corresponds to the right dose. Thus, a wide range of doses should be tested, and this as early as possible during drug development. The first step is to assess the optimum beta-blocking dose in healthy volunteers during phase I studies. These dose-response studies are usually performed according to a cross-over design. Among the many techniques proposed for assessing the effects of beta-blockers in man, isoprenaline and dynamic exercise tests are the most commonly used. The second step is to make use of the previous results to find the right dose for hypertensive patients in phase II studies. However, many individual factors which can influence the blood pressure response should be kept in mind, especially the initial blood pressure level. The choice of the design is generally based on the need to have repeated administration in order to obtain optimum control of the hypertension. Therefore, the cross-over design, although theoretically the best one, is rarely used on account of its practical and ethical problems. In contrast, the parallel design, with random assignment of treatments, is suitable to most experimental situations. Very different in nature, the stepped dose design stems from an ethical and practical approach of dose finding and thus is also widely used. Finally, correct measurement techniques of blood pressure are required.(ABSTRACT TRUNCATED AT 250 WORDS)
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008875:Middle Aged; D011412:Propanolamines / Q000008:administration & dosage*; D013876:Thiophenes
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D013876:Thiophenes; C005632:tertatolol