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Comparative effects of amlodipine and nifedipine GITS during treatment and after missing two doses

Hernández Hernández, Rafaela; Armas-Hernández, Mar´a José; Chourio, José Antonio Colinab; Armas-Padilla, Mar´a Cristina; López, Luisc; Álvarez, Migueld; Pacheco, Beatriza

Clinical Pharmacology
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Objective To compare the antihypertensive efficacy of amlodipine and nifedipine gastrointestinal therapeutic system (GITS) measured by office and ambulatory blood pressure monitoring (ABPM) during treatment and, after patients have missed two doses.

Method After a single blind run-in 4-week placebo period, 58 patients were randomly allocated to amlodipine (5 mg/daily, n =  30) or nifedipine GITS (30 mg/daily;n  = 28) in a double-blind, double dummy fashion. Patients received active medication for 4 weeks. Then, to simulate failure of compliance, patients received two single blinded doses of placebo. Ambulatory blood pressure monitoring was carried out at the end of run-in placebo phase, the first day, the last day of active treatment and up to 72 h after the last active dose.

Results Diastolic blood pressure was controlled in 61.9% patients on amlodipine and 52.9% on nifedipine GITS. Reductions in blood pressure were similar in both groups. ABPM showed significant reduction in blood pressure from the first day in the nifedipine GITS group, while amlodipine group had marginal effect. Peak reduction in systolic/diastolic blood pressure was 26/15 mmHg at 5–6 h after ingestion of amlodipine tablets. The trough reduction was 22/13 mmHg; with a trough-to-peak ratio of 84.61% for systolic and 86.67% for diastolic blood pressure. Peak reduction in systolic/diastolic blood pressure with nifedipine GITS was 19/15 mmHg and the trough reduction was 21/17 mmHg, giving a trough-to-peak ratio of 100% for both systolic and diastolic blood pressure.

When patients received placebo after 4 weeks of active treatment, simulating a compliance failure, amlodipine maintained reduction in systolic and diastolic blood pressure for at least up to 72 h after the last active dose, maintaining 57.71% of the effect for systolic blood pressure and 60.00% for diastolic blood pressure. In contrast, nifedipine GITS effect was rapidly lost during this study phase, with a reduction in systolic and diastolic blood pressure of only 14–16%, 72 h after the last active dose.

Conclusion This study showed that amlodipine and nifedipine GITS reduce blood pressure to about the same extent during chronic treatment. In the case of compliance failure, such as missing one or two doses, amlodipine maintained significant and important antihypertensive effect with the trough-to-peak ratio still over 50% 72 h after the last active dose. On the other hand, the coverage of nifedipine GITS was limited to about 36 h after the last active dose.

a Clinical Pharmacology Unit, Hypertension Clinic, School of Medicine. Universidad Centroccidental Lisandro Alvarado, Barquisimeto, Venezuela b Department of Physiological Sciences, Section of Pharmacology, School of Medicine. University of Zulia, Maracaibo, Venezuela c Policlı´nica “Santiago de León”, Caracas, Venezuela d Cardiovascular Center “Dr Mariano Alvarez” Maturı´n, Venezuela.

Correspondence and requests for reprints to Rafael Hernández Hernández MD, Unidad de Terapia Médica, Calle 55 entre Ave. PL Torres y Carrera 21, Edif. El Bosque. Apto. A01, Barquisimeto, Venezuela. Fax: +58 51 551 098; e-mail: rhernan@cantv.net

Received 8 August 2000

Revised 20 November 2000

Accepted 7 December 2000

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Introduction

Hypertension as a chronic disease requires continuous treatment to control blood pressure and avoid complications from the disease 1. Despite the availability of safe and effective antihypertensive agents, blood pressure continues to be poorly controlled in patients with hypertension, and only a minority of patients achieves recommended blood pressure control levels 2,3. The National Health and Nutrition Examination Survey (1988–1991) revealed that more than 70% of persons with hypertension in whom good blood pressure control is not achieved and termed ‘difficult hypertensives’ are really those who are non-adherent or non-compliant 1,4. Compliance with antihypertensive treatment is very important to protect from the cardiovascular and cerebrovascular complications of hypertension. With once-daily therapy, compliance is improved significantly when compared with two or more doses a day. However, some patients, even with a once-daily regimen do not take treatment on time, and many of them miss one or more doses, and this low compliance is a major cause of poor blood pressure control 5–8. Medication-taking behavior displays marked inter- and intra-subject variability over time. The most frequent deviation of therapy is the random occurrence of underdosing 9,10.

Moronde et al. 11, assessing compliance according to regular prescription refills, reported that partial compliers had a higher rate of re-hospitalization. Psaty 12 reported a higher rate of coronary events among hypertensive patients being treated with β-blockers, with a less than 80% compliance rate.

One alternative to avoid the adverse effect of partial compliance in patients with hypertension consists of using drugs which can be taken at 24 h intervals but with potential to last for a longer time, to compensate for the erratic medication-taking behavior 9. Considering the limitations in human behavior, it is apparent that antihypertensive drugs should not be evaluated only for the efficacy in lowering blood pressure when properly used, but also for the persistence of their antihypertensive effect during intermittent compliance 13.

Calcium channel blockers have been used in the treatment of hypertension for a long time. They show a good correlation between plasma concentration and blood pressure lowering effect 14,15. Verapamil, nifedipine and diltiazem are the first generation calcium channel blockers having in common the pharmacokinetic properties of being well absorbed after oral administration, and having low bioavailability and short half-life.

As a clinical consequence of this pharmacokinetic profile, these drugs have rapid onset and a short duration of action, and therefore they have to be used in three or four doses a day to maintain plasma level and pharmacodynamic effects as stable as possible 16. The first generation agents have been prepared in many slow-release formulations to maintain adequate plasma concentration, prolonging the duration of action, and thereby permitting once-daily dosing.

The dihydropyridine calcium channel blocker, nifedipine, has been formulated as the gastrointestinal therapeutic system (GITS) designed to release the drug into the gastrointestinal lumen at a steady rate for 16–18 h, delaying the release during the first few hours, and permitting once-daily dosing with uniform plasma concentration during the 24 h 17,18.

Amlodipine is a dihydropyridine calcium channel blocker that is absorbed from the gut when given orally. It has good bioavailability and a long half-life of 35–50 h, and is clinically effective when given once a day 19–21.

The aim of this study was to compare the antihypertensive efficacy of amlodipine and nifedipine GITS measured by office and ambulatory blood pressure monitoring (ABPM) during treatment and after the patients have missed two doses.

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Patients and methods

The present study was performed on 58 patients, each of whom was given containers with placebo or active drug. They initially took two placebo tablets, in a single-blind run in a 4-week period. The patients were then randomly allocated to one of the two groups, according to a pre-established computer-generated random table. Patients in the first group (n  = 30) received active 5 mg amlodipine tablets and placebo nifedipine GITS; the other group (n  = 28) received active 30 mg nifedipine GITS tablets and placebo amlodipine tablets, in a double-blind, double-dummy manner. The baseline characteristics of the two groups of patients are presented in Table 1

Table 1

Table 1

Patients who entered the study gave their informed consent. The study was approved by an ethical committee (Institutional Review Board).

Patients were instructed to take one tablet from each container every day at 0700 h, except on the day of their clinic visit. At each visit, new medication was dispensed. Treatment compliance was verified by counting returned tablets at each visit.

All patients included in the study had office sitting diastolic blood pressure between 95–115 mmHg, and ambulatory diastolic blood pressure ≥90 mmHg during the awake period (0600 h to 2200 h). Patients visited the Hypertension Clinic every week, and their blood pressure and heart rate were determined in duplicate in the sitting position. Blood pressure was measured with a mercury sphygmomanometer by using phases I and V of Korotkoff sounds.

The first ABPM was carried out for a period of 24 h, starting at 0700 h during the placebo run-in phase in patients who met the office diastolic blood pressure criteria. Patients who met the second criteria (ABPM) continued to the active phase.

On the first day of the active medication, patients were subjected to the second ABPM for 24 h. After 4 weeks of active treatment, patients had further ambulatory blood pressure monitoring. In this case, patients received active tablets and a blood pressure monitor was attached. New containers with placebo tablets were delivered to patients in a single-blind way. Patients were instructed to take the placebo tablets as usual, and ambulatory blood pressure was monitored up to 72 h after the last active dose.

ABPM was performed in both groups using an oscillometric system (model HM-Revelation; Hill Med, Miami, Florida, USA), starting at 0700 h, immediately after the patients took the tablets. The ambulatory blood pressure monitor was programmed to record blood pressure every 20 min during the time interval of 0600 h to 2230 h, and every 30 min during the interval 2230 h 0600 h. The majority of patients had worn the ABPM unit previously and had been trained to stop muscular activity, and to keep their arm entirely still during blood pressure measurements. Values corresponding to each hour were averaged for each patient for systolic and diastolic blood pressure and heart rate. When values changed by ≥50 or ≥30 mmHg for systolic or diastolic blood pressures within the hour, respectively, the measurement was considered erroneous and not taken into account in the calculations.

Values from ABPM were grouped by hours. Trough-to-peak ratios for 24, 48 and 72 h were calculated by dividing the net changes in systolic and diastolic blood pressure obtained at 23–24; 47–48, and 71–72 h from the last dose of active medication (trough) by the maximum net fall in blood pressure during the first 12 h after the dose.

Office blood pressure values were grouped by treatment. Mean and standard deviation or standard error were calculated for each treatment group. The differences in the effect between drugs and placebo were evaluated by Student's t -test. One way ANOVA test and Bonferroni′s correction was calculated within each group.

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Results

Office blood pressure and heart rate

Thirty patients were included in the amlodipine group and 28 patients in the nifedipine GITS group; two patients in each group withdrew at their own request after completing the placebo phase of the study, for reasons not related to the study or drugs.

Office placebo sitting blood pressure (mean ± standard deviation) was 164 ± 14.41/103 ± 5.64 mmHg for the amlodipine group and 166 ± 14.88/104 ± 4.82 mmHg for the nifedipine GITS group of patients (NS) (Table 1). After 1 week of active treatment, the blood pressure in the amlodipine group was 146 ± 12.4/93 ± 8.20 mmHg and in the nifedipine GITS group, it was 150 ± 12.08/95 ± 9.66 mmHg. At the end of 4 weeks of treatment, the levels decreased to 142 ± 14.05/88 ± 7.27 mmHg and 145 ± 10.42/89 ± 5.88 mmHg, respectively. These values were statistically different from placebo (P  < 0.001) at week 1 and 4, but equivalent between groups (Table 2).

Table 2

Table 2

When patients received two doses of placebo tablets, simulating a failure in compliance, the office blood pressure at 72 h after the last active dose was 145 ± 15.61/93 ± 7.64 mmHg in the amlodipine group (P  < 0.001 from placebo), and 163 ± 16.87/100 ± 8.13 mmHg in the nifedipine GITS group (not significant from placebo) (Table 2).

The changes in systolic and diastolic blood pressure (Table 3) were statistically different from placebo for both groups of patients for both 1 week and 4 weeks of treatment. After 72 h post-active treatment, changes from week 4 indicated an increment of 4.9/6.7 mmHg (systolic/diastolic) for the amlodipine group and 21.42/13.00 mmHg for the nifedipine GITS group. Values were statistically different when compared for the two drugs used in the treatment (P  < 0.001).

Table 3

Table 3

The heart rate was 79 bpm at the end of the placebo phase for both groups of patients (Table 2). The average change in the amlodipine group was +4.6 ± 7.09 bpm (P  < 0.05 from placebo baseline) and +1.5 bpm (NS) after 1 and 4 weeks of treatment. In the nifedipine GITS group, the average increase in the heart rate was +2.84 ± 8.64 bpm (NS) and +4.74 ± 8.44 bpm (P  < 0.02) after 1 and 4 weeks of treatment (Table 3).

Seventy-two hours after the last dose of the active drugs, the change in the heart rate from the values after 4 weeks of active treatment was +0.7 ± 8.14 bpm for the amlodipine group (NS) and –4.68 ± 6.81 for the nifedipine GITS group, P  < 0.01 (P  < 0.03 from amlodipine group) (Table 3).

A reduction in systolic blood pressure below 140 mmHg was obtained in 47.6% of the amlodipine patients, and in 42.1% of the nifedipine GITS patients. A reduction in diastolic blood pressure below 90 mmHg was obtained in 61.9 and 52.6% of patients in the two drug groups, respectively (Table 4); the difference between the two drugs did not reach statistical significance (χ 2 ).

Table 4

Table 4

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Ambulatory blood pressure monitoring

ABPM was carried out in 21 patients in the amlodipine group and in 19 patients in the nifedipine GITS group.

ABPM showed reduction in both the systolic (Fig. 1) and diastolic (Fig. 2) blood pressures for the entire 24-h period in patients treated with either drug for 4 weeks; the reduction in BP was significant (P  < 0.001) as compared with the placebo period. Fig. 1 and Fig. 2 show 24-h blood pressure values after the patient took one or two doses of placebo following 4 weeks of active treatment (simulating a failure of compliance).

Fig. 1

Fig. 1

Fig. 2

Fig. 2

Table 5 shows systolic and diastolic blood pressure grouped every 4 h, during the placebo phase, on the first day of active treatment, after 4 weeks of active treatment and up to 72 h after the last active dose.

Table 5

Table 5

Blood pressure levels are statistically equivalents for any time period for amlodipine and nifedipine GITS groups after treatment for 4 weeks, and also up to 36 h post-active treatment.

During the second and third day of ABPM, after the patients had taken a single-blind placebo tablets instead of the active tablets, simulating a compliance failure, the antihypertensive effect of nifedipine GITS was progressively lost, and blood pressure tended to return to the placebo phase levels. The average blood pressure during the period 0200 h to 0600 h for placebo was 146 ± 3.4/94 ± 2.2 mmHg; during the active treatment: 129 ± 2.7/84 ± 2.4 mmHg; after the first day of missed tablets: 140 ± 3.1/91 ± 2.5 mmHg and after the second day of missed tablets: 143 ± 5.0/92 ± 3.0. On the other hand, in the amlodipine group, the average blood pressure during the period 0200 h to 0600 h was 143 ± 4.1/93 ± 2.5 mmHg; 124 ± 3.1/80 ± 2.0 mmHg; 128 ± 4.1/81 ± 2.0 mmHg and 135 ± 4.0/86 ± 2.3 mmHg, respectively. The blood pressure was statistically different (P  < 0.002/P  < 0.05) when compared to the amlodipine and nifedipine GITS groups at 36–72 h from the time the last active tablet was taken.

The peak effect is observed for systolic and diastolic blood pressure at 4–6 h after the dose of amlodipine, and at 2–6 h after the dose of nifedipine GITS (Table 6). Trough-to-peak ratios of blood pressure during active treatment were 84.61% for systolic and 86.67% for diastolic for the amlodipine group, and 100% (for both systolic and diastolic) for the nifedipine GITS group.

Table 6

Table 6

Trough-to-peak ratios of blood pressure at 72 h after the last active dose of amlodipine were 57.71 and 60.00% for systolic and diastolic and 15.79 and 14.28% for nifedipine GITS, respectively.

Ambulatory heart rates during placebo run-in phase, the first day of active treatment and after 4 weeks of active treatment are shown in Fig. 3. Average heart rate values during the 24 h of placebo run-in phase for amlodipine group were 78.44 ± 2.56 bpm; during the first day of treatment: 79.5 ± 2.35 bpm, and during 4 weeks of active treatment 78.64 ± 2.40; these values were statistically and clinically equivalent. In the nifedipine GITS group, the heart rate was 76.01 ± 2.86 bpm during placebo, 82.46 ± 2.76 bpm (P  < 0.05 from placebo) and 78.9 ± 2.51 respectively for the first day and after 4 weeks of active treatment. The circadian rhythm of heart rate was not modified in any group of patients.

Fig. 3

Fig. 3

Both drugs were well tolerated; no patient withdrew from the study because of side effects. In the amlodipine group, four patients reported headaches, three had dizziness, one an increase in diuresis and one had knee ache. In the nifedipine GITS group, four patients reported headaches, and three others each had dizziness, edema, and palpitations, respectively.

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Discussion

In the present study, a comparison was made between two dihydropyridine calcium antagonists, the short-acting nifedipine in the GITS formulation and the intrinsically long-acting agent, amlodipine. The two drugs given at fixed doses of 30 mg and 5 mg daily, respectively, for 4 weeks in a parallel, double-blind double-dummy fashion.

Based on office blood pressure measurements, the reduction in systolic and diastolic blood pressure was similar for the two drugs, both at 1 week and at 4 weeks of continuous treatment. Reductions from placebo baseline in systolic/diastolic BP were 18.2 ± 11.17/10.2 ± 8.57 mmHg for the amlodipine group and 16.21 ± 14.80/9.96 ± 10.75 mmHg for the nifedipine group after the first week of treatment (Table 3). The reductions were 24.2 ± 15.12/16.0 ± 7.67 mmHg and 23.58 ± 11.67/15.95 ± 6.64 mmHg for the two agents, respectively, after 4 weeks of therapy (Table 3). The reduction in blood pressure was statistically equivalent for the two drugs. However, the percentage of patients whose diastolic blood pressure decreased below 90 mmHg was slightly higher in the amlodipine group (61.9 vs. 52.6%), but the difference did not reach statistical significance. Our results agree with those previously reported. Krakoff 22 reported the effectiveness of nifedipine GITS in a group of 1115 patients with mild to moderate hypertension treated with 30–180 mg daily for up to 18 weeks: in 75% of patients, the diastolic blood pressure reached 90 mmHg or there was a reduction ≥10 mmHg. In a multicenter trial comparing nifedipine GITS, 30–90 mg daily in 91 patients, versus enalapril, 5–40 mg daily in 100 patients, nifedipine caused reduction in systolic/diastolic blood pressure of 21/13 mmHg and blood pressure control was achieved in 80% of patients. The reduction in blood pressure with enalapril was 20/11 mmHg, and control in 77% of patients 23. Control in both studies was defined as reduction of ≥10 mmHg or ≤90 mmHg in diastolic BP 22,23. In our study, nifedipine GITS induce a control of diastolic BP in 52.5% of the patients, being lower than previously found with higher dosage (up to 180 mg daily) and longer trial duration.

In a comparative study conducted in general practice in 4620 patients, amlodipine normalized blood pressure in 70% of patients after 8 weeks of treatments with 5–10 mg daily dose 24. Koenig 25, comparing felodipine and amlodipine in a double-blind, parallel study in 118 patients, reported that amlodipine reduced systolic/diastolic BP by 23/11 mmHg, and controlled hypertension in 75% of patients, with an average daily dose of 7.15 mg. In a double-blind, parallel study, comparing amlodipine (n  = 15) versus enalapril (n  = 15), after 4 weeks of treatment; control of blood pressure was achieved in 54.4% of patients on amlodipine (5 mg daily) with a reduction in blood pressure of 30/17 mmHg, while enalapril (20 mg daily) controlled hypertension in 46.7% of patients with a reduction of 19/11 mmHg in blood pressure 26. In the present study, amlodipine at a fixed dose of 5 mg daily, controlled blood pressure in 61.9% of the patients; these results are similar to those obtained by other investigators.

Based on ABPM, this study shows that both amlodipine and nifedipine GITS, administered once-daily controlled blood pressure during the entire 24-h period and maintained the circadian rhythm of blood pressure and heart rate. Amlodipine reduced systolic/diastolic blood pressure for the 24-h period after 4 weeks of treatment by 19.2/10.7 mmHg, and by 19.1/10.8 mmHg during the awake period, and by 19.5/10.7 mmHg during the sleep period. In an earlier study 26, we reported a reduction of 21.5/13.3 by amlodipine in a group of 15 patients. Similar results were reported by Mroczek et al. 27. In the present study, nifedipine GITS decreased the systolic/diastolic BP by 14.7/8.0 mmHg; 13.3/7.5 mmHg and 17.5/8.8 mmHg for the 24-h awake and sleeping periods, respectively. Zanchetti 28 reported in a group of 25 patients receiving 30 mg daily of nifedipine GITS a reduction of 16.5/10.8 mmHg during the 24 h. In a crossover comparison (in 40 patients) between amlodipine (5–10 mg daily), and nifedipine GITS (30–60 mg daily), Ferrucci et al. 29 observed that amlodipine reduced 24-h ambulatory blood pressure by 22.2/12.6 mmHg, the daytime by 23.3/13.9 mmHg, and the night-time by 18.5/8.0 mmHg. The respective reductions with nifedipine GITS were 17.7/11.4 mmHg, 18.8/13.0 mmHg and 14.0/5.8 mmHg. The reduction in blood pressure in our study was lower because we used lower doses of both drugs. In the Ferrucci et al. study, most patients received either 60 mg of nifedipine GITS or 10 mg of amlodipine.

Maximum reduction of systolic/diastolic blood pressure was 26/15 mmHg at 5–6 h after ingestion of amlodipine tablets; 24 h after ingestion, the reduction in blood pressure (trough) was 22/13 mmHg, giving a trough-to-peak ratio of 84.61% for systolic and 86.67% for diastolic blood pressure. In the study reported earlier 26, peak reduction in blood pressure with amlodipine (7.2 mg daily) was 28.09/20.5 mmHg and the trough was 27.9/17.8 mmHg, with trough-to-peak ratio of 99.4% for systolic blood pressure and 86.7% for diastolic blood pressure.

The corresponding reductions in blood pressure with nifedipine GITS were 19/15 mmHg (peak) and 21/17 mmHg (trough), giving a trough-to-peak ratio of 100% for both systolic and diastolic blood pressure. Zanchetti 28 found a trough-to-peak ratio of 90.5% for systolic and 76.3% for diastolic at 30 mg daily dosage and 109.3 and 98.6% for systolic and diastolic at a higher dose (60 mg), respectively. Therefore, both drugs reduce blood pressure during the entire 24-h period during chronic administration.

In our study, when patients received placebo after 4 weeks of active treatment simulating a compliance failure, amlodipine maintained reduction in systolic and diastolic blood pressure for at least 72 h after the last active dose, retaining 73.08 and 57.71% of the effect for systolic blood pressure and 73.33 and 60.00% for diastolic blood pressure, respectively at 48 and 72 h. These values are above the 50% recommended trough-to-peak ratio for controlling hypertension 30,31 even 72 h after the last active dosage.

In contrast, the antihypertensive effect of nifedipine GITS was rapidly lost, as the reduction in systolic/diastolic blood pressure at 48 h was 42.10 and 53.33% and only 15.79 and 14.28% at 72 h after the last active dose. As shown in Fig. 2 and Fig. 3, blood pressure started to rise importantly after 36 h from the last nifedipine GITS tablet, Our results are in agreement with those reported earlier 27,31 where the antihypertensive effect of nifedipine GITS lasted 30–36 h.

The onset of antihypertensive action of nifedipine GITS is more rapid than that of amlodipine. The reduction in blood pressure on the first day of therapy with nifedipine GITS was accompanied by a small but significant rise in heart rate, indicating sympathetic activation as a consequence of vasodilation. A reduction in blood pressure is observed only after 12 h from the first administration of amlodipine, but there was no increase in heart rate suggesting that amlodipine lowers blood pressure without increasing sympathetic activity, as has been reported previously 32.

The difference between the duration of effect could be explained by the pharmacokinetic profiles of the two drugs. Nifedipine is a short-acting agent with a short t-max (time to achieve maximum plasma levels) and a short half-life. However, the GITs formulation produces stable blood levels of nifedipine for the entire 24-h period, as has been reported previously 33 and shown by the present study. But when the patients miss one or two doses, blood level of nifedipine drops, which results in the rapid loss of the pharmacodynamic and antihypertensive effect. On the other hand, amlodipine is an intrinsically long-acting drug, with a long t-max (6–9 h) and a long half-life of 35–50 h 14. When steady-state plasma amlodipine concentrations are reached during chronic treatment, and the drug is stopped, such as by missing one or two doses due to failure in compliance, blood levels are maintained within the therapeutic range for a long time 34,35. This translates into long pharmacodynamic and antihypertensive effect.

The calcium antagonists, amlodipine and nifedipine, do not have an antihypertensive effect persisting beyond what their pharmacokinetic profile would indicate. The antihypertensive effect seems to correlate well with plasma levels 14 either at the beginning or during chronic therapy 15. Short-acting calcium antagonists, such as nifedipine, can be reformulated in slow-release preparations that can maintain antihypertensive effect for the entire 24 h, but these formulations may not permit a persistent therapeutic coverage during short periods of compliance as shown by the present study. On the contrary, intrinsically long half-life agents such as amlodipine can extend the therapeutic coverage when an occasional failure in compliance occurs.

In conclusion, this study shows that both amlodipine and nifedipine GITS reduce blood pressure to about the same extent during chronic treatment, with similar efficacy. Nifedipine GITS could produce mild but significant sympathetic stimulation especially at the beginning of therapy. During short periods of failure of compliance, such as missing one or two doses, amlodipine (5 mg daily) maintains antihypertensive effect for at least 72 h after the last active dose, with trough-to-peak ratio still over 50%. On the other hand, the effective coverage of nifedipine GITS (30 mg daily) is limited to 36 h after the last active dose. Our studies suggest that patients who are habitually partially compliant may be treated with amlodipine rather than nifedipine GITS to avoid an abrupt rise in blood pressure as a result of temporary non-compliance during chronic therapy.

We are most grateful to Dr Zafar Israili for helping us in the preparation of the manuscript. Partial support was given by CDCHT/UCLA Venezuela (No. 02-IM-00). Pfizer S.A. sponsored the study reported.

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Keywords:

amlodipine; nifedipine GITS; ambulatory blood pressure monitoring; compliance

© 2001 Lippincott Williams & Wilkins, Inc.