Antihypertensive effectiveness of the valsartan and its influence on morning surge in patients with mild to moderate arterial hypertension

AJH–May 2003–VOL. 16, NO. 5, PART 2

chronotherapeutic formulation of propranolol designed for nighttime dosing, had appropriate pharmacokinetics to provide maximum effect in the morning. Beta-blockers may be well-suited for the purpose of chronotherapy since they attenuate sympathetic activity and thereby decrease the increase in heart rate and contractility that are seen upon waking. Methods: Pharmacokinetics of propranolol CR and Inderal LA following single and multiple doses were determined in normal male volunteers in this open-label, two-period, crossover study. The drugs were dosed in the evening and serial blood samples were taken for determination of propranolol concentration the next 24 to 72 hours. Results: Following a single 160 mg dose of propranolol CR administered at 10 PM, absorption was delayed by about 4 hrs, after which plasma concentration rose steadily, reaching a peak at about 10 AM. In contrast, after dosing with Inderal LA, plasma levels of propranolol began to rise almost immediately, reaching a plateau between 4 AM and 10 AM. During multiple dosing, steady-state trough plasma concentrations were achieved after 2 days with either drug. Following the final dose, the changes in plasma concentration were similar to those observed in the single dose study. Bioavailability was similar for both formulations of propranolol. In conclusion, Propranolol CR exhibited appropriate pharmacokinetics for the chronotherapeutic treatment of hypertension; moreover, the higher peak plasma levels and the slightly greater bioavailability observed after dosing with propranolol CR offer potential advantages over Inderal LA.

POSTERS: Antihypertensive Drugs

129A

and ambulatory blood pressure monitoring (ABPM). The smoothness index (SI) was calculated as ration of the average BP decreasing to its standard deviation. The amplitude of the morning SBP and DBP increasing was calculated according to formula: BPmax. (during 4 hr after awaking) – BPmin (at night). The velocity (MV) of the morning SBP and DBP increasing was calculated as ration of the its amplitude to time between measurements. All patients wrote the diary with awaking time fixation. Valsartan was administered in initial dose 80 with up-titration to 160 mg. Duration of treatments was 3 months. Results: the average office SBP/DBP decreasing was 23 and 13 mmHg. 24-hour, day-time and night-time SBP/DBP diminishing were 17/10, 18/10 and 10/8 mm Hg respectively. Also we noted significant decreasing of the time and pressure load indices. The SI was 0.93⫾0.06 for SBP and 1.03⫾0.06 for DBP. The amplitude of the morning SBP increasing diminished from 69.3⫾5.8 to 43.8⫾5.6 mm Hg. The MV for SBP and DBP declined from 13.9⫾2.2/12.8⫾1.2 to 7.2⫾1.1/7.4⫾1.1 mmHg/hr. Conclusion: in patients with mild to moderate arterial hypertension valsartan was effective and safe antihypertensive drug, that provided smooth 24-hour blood pressure control and decreased the degree of the blood pressure increasing in early morning time. Key Words: valsartan, morning surge, antihypertensive effectiveness

P-254 BLOOD PRESSURE AND PULSE PRESSURE LOWERING EFFECTS, TROUGH: PEAK RATIO AND SMOOTHNESS INDEX OF TELMISARTAN COMPARED TO LISINOPRIL George S. Stergiou, Stamatis P. Efstathiou, Leonidas G. Roussias, Theodore D. Mountokalakis. Hypertension Center, Third University Dept of Medicine, Sotiria Hospital, Athens, Greece.

Key Words: propranolol, chronotherapy, circadian rhythm

P-253 ANTIHYPERTENSIVE EFFECTIVENESS OF THE VALSARTAN AND ITS INFLUENCE ON MORNING SURGE IN PATIENTS WITH MILD TO MODERATE ARTERIAL HYPERTENSION Yuriy N Sirenko, Ganna D Radchenko, Vlodimir N Granich, Sergey A Polischuk, Petro I Sidorenko. Secondary Hypertension, Institute of Cardiology, Kiyv, Ukraine. Objective: to evaluate antihypertensive effectiveness of the valsartan and its influence on the morning surge in mild to moderate hypertensive patients. Patients and Methods: in study there were included 42 patients with average systolic (SBP) and diastolic (DBP) 159.7⫾3.4 and 100.3⫾2.7 mmHg. Average age was 50.3⫾2.7 yr., duration of hypertension – 6.2⫾0.3 yr. All patients were done office blood pressure measurement

The objective of the study was to compare the angiotensin converting enzyme inhibitor lisinopril with the angiotensin receptor blocker telmisartan, in regard to their effect on blood pressure (BP) and pulse pressure (PP), and the duration and the homogeneity of their antihypertensive effect. Thirty-two untreated hypertensives with elevated ambulatory BP were randomized to receive lisinopril 20 mg o.d. or telmisartan 50 mg o.d. for 5 weeks, and were subsequently crossed-over to the alternative treatment for a second 5-week period. Measurements of clinic and 24-hour ambulatory BP were performed before randomization and at the end of each randomized treatment period. Trough: peak ratio (TPR) and smoothness index (SI) were calculated for each drug for the responders only (subjects with ⱖ6 mmHg fall in diastolic 24-hour ambulatory BP at peak). Using both measurement techniques no difference was detected between the two drugs in their effects neither on BP (mean difference in clinic BP -0.1⫾11.1/0.7⫾6.3 mmHg, for systolic/diastolic, and in 24hour ambulatory BP 1.2⫾7.1/0.7⫾5.1 mmHg) nor on PP (mean difference in clinic PP -0.8⫾8.5 mmHg, and in 24-hour ambulatory PP 0.5⫾3.5 mmHg). Furthermore, there was no difference between the TPR and the SI values of telmisartan (TPR 0.85/0.61 for systolic/diastolic BP and SI 1.46/1.2) and lisinopril (TPR 0.74/0.64 and SI 1.3/1.17). These data suggest that telmisartan is as effective as lisinopril in reducing BP and PP. Both drugs seem to provide smooth and sustained effects throughout the full 24-hour period. Key Words: pulse pressure, smoothness index, trough: peak ratio