Timing for administration of an antihypertensive drug in the treatment of essential hypertension.

Abstract

To find the best timing for administration of long-acting antihypertensive drugs, we gave nitrendipine, a calcium antagonist of the dihydropyridine group, once a day to six hospitalized and drug-free patients with essential hypertension, changing the time of administration and studying the effects on the circadian rhythm of blood pressure. After control values of 24-hour blood pressure variations were taken with patients on placebo, a 10-mg tablet of nitrendipine was given for 3 days on three occasions -at 6 AM on awakening, at 8:30 AM after breakfast, and at 6 PM after supper; 24-hour blood pressure values for each period were recorded on the third day. The 24-hour blood pressure values during the control period showed a biphasic circadian rhythm, with higher values during wakefulness and lower values during sleep. The control period was also characterized by a rapid rise in blood pressure on awakening, the so-called morning surge of blood pressure, and a gradual decline during sleep at night. Although the morning surge was not completely suppressed by nitrendipine given after breakfast, it was diminished by the drug given on awakening or after supper, the latter brought a deeper decline in blood pressure during sleep compared with other times. The average of 24-hour blood pressure values obtained by nitrendipine given on awakening was the lowest among the three occasions. Thus, administration of long-acting calcium antagonists with a rapid onset of action on awakening in the early morning seems to be a more rational and beneficial alternative than the conventional administration after breakfast. The earlier administration may prevent dangerous cardiovascular catastrophes, including stroke, myocardial infarction, and sudden death, known to occur often during the morning surge of blood pressure. 91214 have been shown to increase between the hours of 6 and 9 AM compared with the rest of the day. A number of precipitating factors may be involved in these early morning catastrophes, but the marked rise in blood pressure almost certainly is a major factor, perhaps by causing a rupture of atherosclerotic plaques whereby thrombus is formed. 9 Antihypertensive drugs that are given once a day have come into common use in the treatment of essential hypertension. Nitrendipine is one of the long-acting calcium antagonists of the dihydropyridine group whose clinical usefulness in the treatment of essential hypertension has been established either as monotherapy 1517 or in combination with /J-blockers. 18 Nitrendipine has a rapid onset of action and is usually given once or twice From the Department of Internal Medicine III, Kumamoto (Japan) University Medical School.Correspondence to Teruhisa Umeda, MD, Department of Internal Medicine III, Kumamoto University Medical School, 1-1-1 Honjo, Kumamoto 860, Japan. a day. Pharmacokinetic studies on dihydropyridine calcium antagonists performed in hypertensive patients 19 ' 20 have also found a relatively straight correlation between the logarithmic value of the pla...

Dose‐ And Administration Time‐Dependent Effects Of Nifedipine Gits On Ambulatory Blood Pressure In Hypertensive Subjects

“…Several trials have investigated the differential effects of morning versus evening administration of CCB, including amlodipine (Lemmer et al, 2003;Mengden et al, 1992;Nold et al, 1998;Qiu et al, 2003), cilnidipine (Kitahara et al, 2004), diltiazem (Kohno et al, 1997), isradipine (Fogari et al, 1993;Portaluppi et al, 1995), nifedipine (Greminger et al, 1994), nisoldipine (White et al, 1999), and nitrendipine (Meilhac et al, 1992;Umeda et al, 1994). Dihydropyridine derivatives seem to reduce BP homogeneously during the day and night independent of dosing time (Hermida & Smolensky, 2004;Hermida et al, 2005).…”

The importance of biological rhythms in drug treatment of hypertension and sex-dependent modifications

“…*P morning versus evening at least ,0.05; profile remained unaffected or slightly changed after evening dosing. [120][121][122][123] Most interestingly, the greatly disturbed BP profile in secondary hypertensives (nondippers) due to renal failure was normalized after evening but not after morning dosing of isradipine. 119,123,124 Similarly, amlodipine ( Figure 5) and nisoldipine extended release transformed nondippers into dippers, but after both evening and morning dosing, 38,119,124,125 which might be due to the longer "apparent" half-life of these drugs.…”

Chronobiology and Chronotherapy of Hypertension – A Review

“…A single morning dose of a sustained-release verapamil showed a good 24-hour BP control 44. Dihydropyridine derivatives [DHP] differing in pharmacokinetics, seem to reduce BP to a varying degree during day and night, drug formulation and dosing interval may play an additional role. In eight studies in essential hypertensives using a cross-over design, DHP did not differently affect the 24-hour BP profile after once morning or once evening dosing [45][46][47][48][49][50][51][52][53] . Most interestingly, the greatly disturbed BP profile in secondary hypertensives due to renal failure was only normalized after evening but not after morning dosing of isradipine 54 .…”

“…For chronopharmacodynamics of calcium channel blockers (CCB) several trials have investigated the differential effects of morning vs. evening administration of CCB, including amlodipine, cilnidipine, diltiazem, isradipine, nifedipine, nisoldipine, and nitrendipine in diurnally active subjects [63][64][65][66][67][68][69][70][71][72][73][74][75] . A sustained-release formulation of diltiazem was found to be more effective in controlling the 24-hour BP mean when administered at night, while also reducing the diurnal/nocturnal BP ratio towards a more nondipper profile.…”