Effect of Morning and Bedtime Dosing with Cilnidipine on Blood Pressure, Heart Rate, and Sympathetic Nervous Activity in Essential Hypertensive Patients

Abstract

Cilnidipine has a blocking action against N-type calcium channels as well as L-type calcium channels. We studied the effect of morning and bedtime dosing on circadian variation of blood pressure (BP), heart rate (HR), and activity of the autonomic nervous system, using an open randomized crossover study in 13 essential hypertensive patients. An automated device allowed 24-hour monitoring of ambulatory BP and HR and the power spectrum of the R-R interval, at the observation period, the morning dosing regimen, and the bedtime dosing regimen. Morning dosing and bedtime dosing with cilnidipine reduced the average systolic BP over 24 hours, during daytime, and during nighttime. The average HR and the average LF/HF ratio over 24 hours, during daytime, and during nighttime, were similar for the three periods. Both morning and bedtime dosing reduced the maximum systolic BP in the early morning and suppressed the morning rise of BP, which were accompanied by partial inhibition of the increase in LF/HF ratio. Our results show that cilnidipine administered once daily is an efficient antihypertensive drug regardless of the time of dosing, without reflex tachycardia and increase in sympathetic nervous activity, and with partial inhibition of the morning activation of the sympathetic nervous system.

Fixed-combination of amlodipine and diuretic chronotherapy in the treatment of essential hypertension: improved blood pressure control with bedtime dosing—a multicenter, open-label randomized study

“…However, not all calcium-channel blockers exhibit different efficacies with different dosing-times. Kitahara et al 18 did not find a differential dosing-time effect on cilnidipine during an open, randomized cross-over study. 18 A loop diuretic (torasemide) given in the morning or at bedtime was found to be more efficacious when administered at bedtime.…”

“…Kitahara et al 18 did not find a differential dosing-time effect on cilnidipine during an open, randomized cross-over study. 18 A loop diuretic (torasemide) given in the morning or at bedtime was found to be more efficacious when administered at bedtime. The time-response curves also indicated complete 24-h therapeutic coverage only when torasemide was administered at bedtime.…”

“…[10][11][12][13] Studied CCBs include amlodipine, 10,17 diltiazem, 11 and cilnidipine. 18 Portaluppi et al 19 explored the relative advantage of evening vs. morning once-a-day treatment with a conventional sustained-release isradipine formulation in non-dipper hypertensive patients with chronic renal failure and found that an evening dosing schedule best reduces and normalizes nocturnal SBP and DBP. However, not all calcium-channel blockers exhibit different efficacies with different dosing-times.…”

“…[17][18][19][20]31,32 The retrospective Syst-Eur 25 and HOPE 33 outcome trials show that evening administration of nitrendipine and ramipril impacts sleep-time blood pressure by converting the 24-h blood pressure pattern to a dipper pattern and decreasing CVD risk in the HOPE study. The CONVINCE trial 34,35 did not show a chronotherapy benefit, but the MAPEC trial 36 results suggest that night time dosing is beneficial.…”

Non-dipping morning blood pressure and isolated systolic hypertension in elderly

“…The specifi c T-and N-type calcium antagonist, who inhibits catecholamine release, is a possible candidate (24). Azelnidipine, another calcium antagonist, lowers the heart rate signifi cantly when compared to amlodipine.…”