Ambulatory blood pressure profiles in essential hypertensives after treatment with a new once daily nifedipine formulation.

The antihypertensive efficacy of a new controlled-release preparation of nifedipine developed for once daily administration was investigated in comparison with a standard therapy with sustained-release nifedipine given twice daily in a randomised, open crossover trial. Twenty-two patients with mild to moderate essential hypertension were enrolled. Ambulatory blood pressure monitoring (ABPM) was performed after a wash-out period and after a 3 weeks treatment with 40 mg controlled-release nifedipine once daily and 20 mg sustained-release nifedipine twice daily, respectively. ABPM data were evaluated by conventional linear analysis and by rhythm analysis. Both once daily and twice daily administration of nifedipine significantly reduced systolic blood pressure during the daytime and during the night when compared with baseline. The 24-h diastolic blood pressure was significantly decreased by both treatments, but only the once daily regimen significantly lowered both diastolic daytime and night-time means. Comparing systolic and diastolic blood pressures after both treatments, however, no significant differences were obtained. Both nifedipine treatments did neither greatly modify the circadian blood pressure pattern nor reflexly increase heart rate. In conclusion, once daily application of the controlled-release formulation of nifedipine resulted in a consistent and significant blood pressure reduction. Once daily and twice daily medications of nifedipine were about equally effective in lowering the elevated blood pressures.

Morning versus evening amlodipine treatment: effect on circadian blood pressure profile in essential hypertensive patients.

OBJECTIVE: To determine the antihypertensive efficacy and the potential impact on circadian blood pressure pattern of morning versus evening administration of amlodipine to essential hypertensive patients. METHODS: Twelve mild-to-moderate essential hypertensives were investigated in this open, randomized cross-over study. Blood pressure and heart rate were measured by use of ambulatory blood pressure monitoring after a wash-out period of 1 week and after treatment schedules with 5 mg amlodipine once a day either at 0800 h or at 2000 h for 3 weeks. Effects were evaluated by linear and rhythm analysis using the ABPM-FIT program. RESULTS: Both morning and evening administrations of amlodipine significantly (P < 0.01) reduced the elevated systolic and diastolic blood pressures during daytime. However, due to baseline values being lower during night-time, a significant (P < 0.05) reduction was observed only in systolic, not in diastolic, blood pressure. Maximal blood pressure values were significantly (P

Effects of age on circadian blood pressure and heart rate rhythms in patients with primary hypertension.

To evaluate whether circadian rhythms in blood pressure and heart rate are influenced by age, we analyzed 24-h ambulatory blood pressure and heart rate recordings from 31 patients with primary hypertension. Data were collected during hospitalization, after a drug-free run-in period. Set times were administered for lights-on, meals, and lights-off. Daytime napping was prohibited. The patients were divided into sex-matched groups of young (group I: 25-45 years, n = 9), middle-aged (group II: 47-57 years, n = 11), and old (group III: 57-74 years, n = 11) subjects. Hourly data were analysed by fitting a two-component cosine function (24- and 12-h periods). Amplitudes of the circadian rhythms in systolic blood pressure and heart rate were significantly reduced with age. This finding could be partly attributed to the recording of higher nocturnal values in older patients. Elderly hypertensives also evidenced a significantly greater ultradian component (12-h period) in the systolic blood pressure rhythm than did young patients, with the secondary afternoon decline in blood pressure being more pronounced in groups II and III. The 24-h acrophase of heart rate was found to occur approximately 1.6 h earlier than that of systolic blood pressure in the young group (p < 0.01). This phase advance of heart rate compared with systolic blood pressure was reduced to 1 h in group II (p < 0.05) and was not evident in group III (p > 0.1). These results indicate that circadian blood pressure and heart rate profiles of primary hypertensives change with age. Since measures were obtained in a typical clinical setting, these findings have implications for the diagnosis and treatment of hypertension in the elderly. The marked afternoon decline in blood pressure for the elderly patients may also render conventional cosinor analysis inappropriate for accurate description of the circadian rhythms of geriatric hypertensives.

Circadian changes in estimated hepatic blood flow in healthy subjects.

Intravenous injections of indocyanine green (ICG) were given to 10 healthy supine subjects at 02.00, 08.00, 14.00 and 20.00 h. ICG plasma half-life, plasma clearance and estimated hepatic blood flow (EHBF), but not volume of distribution, varied significantly with time of day with EHBF being greatest at 08.00 h. This circadian rhythm in EHBF should be considered when evaluating the kinetics of high-clearance drugs at different times of day.

Chronopharmacokinetics and cardiovascular effects of nifedipine.

Circadian phase dependency in pharmacokinetics and hemodynamic effects on blood pressure and heart rate of different galenic formulations of nifedipine (immediate-release, sustained-release, and i.v. solution) were studied in healthy subjects or in hypertensive patients. Pharmacokinetics of immediate-release but not sustained-release and i.v. nifedipine were dependent on time of day: immediate-release nifedipine had higher Cmax (peak concentration) and shorter tmax (time-to-peak concentration) after morning than evening application, and bioavailability in the evening was reduced by about 40%. Circadian rhythm in estimated hepatic blood flow as determined by indocyanine green kinetics may contribute to these chronokinetics. A circadian time dependency was also found in nifedipine-induced effects on blood pressure and heart rate as monitored by 24-h ambulatory blood pressure measurements. In conclusion, the dose response relationship of oral nifedipine is influenced by the circadian organization of the cardiovascular system as well as by the galenic drug formulation.