Choosing the Right Dose for Beta-Blocker Treatment of Hypertension: Experience with Tertatolol

Abstract

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 β-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 β-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 β-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. In this respect, accuracy of evaluation is markedly improved by automated noninvasive methods which allow a 24-hour recording of blood pressure and minimize the placebo effect by suppressing the subjective aspects of measurement. From this methodology applied to tertatolol, a new β-blocking drug, 5 mg was found to be the optimum dose in antihypertensive treatment. This dose caused an effective reduction in blood pressure both at rest and on exercise, a 24-hour antihypertensive activity and a high incidence of hypertension control both in short-term and long-term therapy. Thus, 5 mg tertatolol administered once daily may be recommended in the treatment of mild to moderate hypertension.

Antihypertensive Effects of Tertatolol: 3-Month Comparative Study against Acebutolol

“…As also shown in other papers on this issue [4][5][6], the average therapeutic dose of tertatolol is 5 nig, given as a single daily administration. However, it is important that the activity and acceptability of any molecule under development be compared not only with those of pla cebo but also, if possible, with those of other agents from the same therapeutic class.…”

“…In man, the dose of 5 mg once daily has been shown to exert an efficient antihypertensive effect all over the 24 h [4][5][6].…”

Long-Term Experience with Tertatolol in Hypertension

“…ß-blockers, introduced in 1964 by Prichard, are presently the most frequently used antihypertensive drugs because of their efficacy, good acceptability and simplicity of administration [3,4], In recent short-term studies [5][6][7], tertatolol, a new potent ß-blocking drug, was shown to be efficient and well accepted at the dose of 5 mg orally once daily. It was nevertheless necessary, since hypertension needs a long term therapy, to appraise its effects on a large range of patients and over a long period of time.…”