Dynamics of beta‐adrenoceptor blockade with cetamolol.

Coelho, Jaime B.; Schnelle, K; Joubert, L; Ventura, Daniel; Mullane, John F.

doi:10.1111/j.1365-2125.1985.tb02663.x

Cited by 7 publications

(1 citation statement)

References 5 publications

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“…They are usually performed in young healthy subjects according to a cross-over design [18][19][20][21][22] which appears to be the most sensitive way to detect between dose differences. The practical approach to this methodology has been recently reviewed in detail [23], Only 2 major conditions re quired for ensuring both its effectiveness and reliability will be recalled: a sufficient wash-out period to avoid a carry-over effect and a random assignment of treat ments.…”

Section: Phase I Studiesmentioning

confidence: 99%

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

et al. 1986

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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.

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Section: Phase I Studiesmentioning

confidence: 99%

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

et al. 1986

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Antihypertensive Efficacy of Cetamolol: A Dose‐Titrated Study

Klausner¹,

Sanghvi²,

Mullane³

et al. 1988

The Journal of Clinical Pharma

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This double-blind, placebo-controlled, randomized multicenter study evaluated the antihypertensive efficacy and safety of cetamolol hydrochloride in 108 patients diagnosed as having mild to moderate hypertension. After a placebo lead-in period, patients received either cetamolol 5-10-15 mg/d (low dose), cetamolol 15-25-50 mg/d (high dose), or placebo, once daily for four weeks. Patients began at the lowest dose and were titrated to higher doses based on the first two assessments of diastolic blood pressure and heart rate, which were conducted each week after double-blind treatment was dispensed. After four weeks of treatment 82.4%, 81.3%, and 93.3% of the low-dose group, high-dose group, and placebo group, respectively, were titrated to the maximum dose level. After four weeks of treatment and 24 hours since the patient's last dose, both cetamolol groups showed a significantly greater (P less than or equal to .05) reduction in supine systolic/diastolic blood pressure (-18.1 +/- 2.3/-9.2 +/- 1.5 mm Hg [low dose] and -17.3 +/- 2.3/-8.3 +/- 1.6 mm Hg [high dose]) than the placebo group (-9.9 +/- 2.5/-3.5 +/- 1.7 mm Hg). In general, the changes in standing (stabilized) systolic and diastolic blood pressure were similar to those seen in supine measurements. Significantly more patients receiving cetamolol than those receiving placebo showed a "good response" (a decrease in diastolic blood pressure of 10 mm Hg or more or measuring less than 90 mm Hg with a decrease of at least 4 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

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Cardioselectivity of Cetamolol Compared With Atenolol and Nadolol

Klausner¹,

Ventura²,

Coelho³

et al. 1988

The Journal of Clinical Pharma

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The selectivity of the beta-adrenoceptor blockade produced by single oral doses of cetamolol, atenolol, and nadolol was compared in normal male subjects. Study 1 established the dose at which each drug provides equivalent beta-1 blockade. Beta-1 blockade was estimated using the degree of inhibition of the increased heart rate (HR) response to graded exercise. Cetamolol (30 mg), atenolol (100 mg), and nadolol (80 mg) all attenuated the HR response to a comparable extent. This result established that the dose ratio of cetamolol:atenolol:nadolol of 1.00:3.33:2.67 provides equipotent beta-1 blockade. This ratio of doses was used in Studies 2 and 3 to evaluate the antagonism of beta-2-mediated responses to titrated doses of intravenous isoproterenol (ISO) by low and high doses of each drug. Beta-2 blockade was assessed using the attenuation of ISO-induced reductions in diastolic blood pressure (DBP) in Study 2 and ISO-induced increases in specific airway conductance (sGAW) in Study 3. For within drug comparisons, antagonism of the HR increase induced by ISO (a response mediated by both beta-1 and beta-2 receptors) was also examined. Treatments included cetamolol (15 and 60 mg), atenolol (50 and 200 mg), and nadolol (40 and 160 mg in Study 2; 40 mg only in Study 3). All drugs tested suppressed the HR, DBP, and sGAW responses to ISO, and this blockade was dose dependent. Cetamolol and nadolol produced approximately equipotent beta-1 blockade, whereas cetamolol at both doses produced a less potent beta-2 blockade. Atenolol antagonized ISO effects on all parameters less than either cetamolol or nadolol. Quantitative cardioselectivity indices revealed that cetamolol 60 mg was the most cardioselective and nadolol 40 mg the least. Data from the three studies demonstrate that cetamolol is cardioselective relative to nadolol and that, in contrast to atenolol, cardioselectivity appears to increase at the higher dose.

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Dynamics of beta‐adrenoceptor blockade with cetamolol.

Cited by 7 publications

References 5 publications

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

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

Antihypertensive Efficacy of Cetamolol: A Dose‐Titrated Study

Cardioselectivity of Cetamolol Compared With Atenolol and Nadolol

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