A 2015 systematic comparison of all clinically used angiotensin-converting enzyme (ACE) inhibitors, found that most ACE inhibitors are rapidly absorbed with maximum bioavailability being reached within 30 minutes to 6 hours depending on the specific ACE inhibitor and dose.1 Elimination half-life ranges from about 2 to 24 hours.
|
ACE Inhibitor
|
tmax
h
|
t1/2
h
|
|
Benazepril/Benazeprilat
|
0.5/1.5
|
10
|
|
Captopril
|
1-1.5
|
<2
|
|
Enalapril/Enalaprilat
|
1/3-4
|
11
|
|
Fosinopril/Fosinoprilat
|
2.8
|
11
|
|
Lisinopril
|
7
|
13
|
|
Moexipril/Moexiprilat
|
1/1.5
|
2-9
|
|
Perindopril/Perindoprilat
|
2/2.4
|
10
|
|
Quinapril
|
0.63
|
2
|
|
Ramipril/Ramiprilat
|
0.7/2.1
|
17
|
|
Trandolapril/Trandolaprilat
|
0.5/6
|
24
|
Table 1: ACE inhibitor maximum bioavailability and elimination half-life1
Most of the ACE inhibitors control blood pressure for 24 hours with a once or twice daily dosing one hour before meals.2-12 After oral dosing, ACE inhibitors are absorbed rapidly (time for peak plasma levels=0.5 – 6 hours) with a wide range of bioavailability (10% for trandolapril to 75% for captopril).1
Most ACE inhibitors can be taken with or without food including benazepril, enalapril, fosinopril, lisinopril, quinapril, ramipril, and trandolapril.2-4,7-9,12
Three ACE inhibitors, captopril, moexipril, and perindopril should be taken on an empty stomach at least one hour before a meal or two hours after a meal to maximize bioavailability.5,6,11
A 2011 Cochrane meta-analysis reviewed five randomized controlled trials which compared the administration-time-related effects of evening with morning dosing in patients with primary hypertension.13 Analysis of mean difference in evening versus morning dose regimen found no statistically significant differences in 24-hour blood pressure. Evening doses reduced 24-hour systolic blood pressure by -0.93 mm Hg (95% confidence interval [CI] [-3.11 – 1.24]) and 24-hour diastolic blood pressure by -1.56 mm Hg (95% CI [-3.18 – 0.06]).
Many small sample-size studies that compared the 24 hour antihypertensive effects of morning versus evening dose regimens had conflicting conclusions.14-22 Some studies suggest that morning administration is preferable as it covers the whole 24 hours better than an evening dose.14-16 Other studies found an evening dose regimen had a better antihypertensive effect throughout a 24-hour period.17-19 Some studies comparing patients taking morning versus evening doses of long-acting ACE inhibitors did not find statistically significant differences between the groups in morning and evening systolic blood pressure.20-22
References
- Regulski M, Regulska K, Stanisz BJ, et al. Chemistry and pharmacology of angiotensin-converting enzyme inhibitors. Curr Pharm Des 2015; 21 (13): 1764-1775.
- Prinivil [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2016.
- Trandolapril [package insert]. Laurelton, NY: Epic Pharma, LLC; 2017.
- Fosinopril sodium [package insert]. Miami, FL: Ciplo USA Inc; 2015.
- Moexipril hydrochloride [package insert]. Teva Pharmaceuticals USA Inc; 2016.
- Aceon [package insert]. North Chicago, IL: Abbot Laboratories; 2011.
- Altace [package insert]. New York, NY: Pfizer Laboratories; 2017.
- Lotensin [package insert]. Parsippany, NJ: Validus Pharmaceuticals LLC; 2014.
- Vasotec [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; 2015.
- Zestril [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP 2014.
- Capoten [package insert]. Spring Valley, NY: Par Pharmaceutical Companies, Inc.; 2012.
- Accupril [package insert]. New York, NY: Parke Davis, Pfizer; 2017.
- Zhao P, Xu P, Wan C, Wang Z. Evening versus morning dosing regimen drug therapy for hypertension. Cochrane Database Syst Rev 2011; (10): Cd004184.
- Palatini P, Mos L, Motolese M, et al. Effect of evening versus morning benazepril on 24-hour blood pressure: A comparative study with continuous intraarterial monitoring. Int J Clin Pharmacol Ther Toxicol 1993; 31 (6): 295-300.
- Myburgh DP, Verho M, Botes JH, Erasmus TP, Luus HG. 24-hour blood pressure control with ramipril: Comparison of once-daily morning and evening administration. Curr Ther Res Clin Exp 1995; 56 (12): 1298-1306.
- Zaslavskaia RM, Narmanova OZ, Teiblium MM, Kalimurzina BS. [time-dependent effects of ramipril in patients with hypertension of 2 stage]. Klin Med (Mosk) 1999; 77 (10): 41-44.
- Palatini P, Racioppa A, Raule G, Zaninotto M, Penzo M, Pessina AC. Effect of timing of administration on the plasma ACE inhibitory activity and the antihypertensive effect of quinapril. Clin Pharmacol Ther 1992; 52 (4): 378-383.
- Hermida RC, Ayala DE. Chronotherapy with the angiotensin-converting enzyme inhibitor ramipril in essential hypertension: Improved blood pressure control with bedtime dosing. Hypertension 2009; 54 (1): 40-46.
- Morgan T, Anderson A, Jones E. The effect on 24 h blood pressure control of an angiotensin converting enzyme inhibitor (perindopril) administered in the morning or at night. J Hypertens 1997; 15 (2): 205-211.
- Kuroda T, Kario K, Hoshide S, et al. Effects of bedtime vs. Morning administration of the long-acting lipophilic angiotensin-converting enzyme inhibitor trandolapril on morning blood pressure in hypertensive patients. Hypertens Res 2004; 27 (1): 15-20.
- Weisser K, Schloos J, Lehmann K, Dusing R, Vetter H, Mutschler E. Pharmacokinetics and converting enzyme inhibition after morning and evening administration of oral enalapril to healthy subjects. Eur J Clin Pharmacol 1991; 40 (1): 95-99.
- Macchiarulo C, Pieri R, Mitolo DC, Pirrelli A. Management of antihypertensive treatment with lisinopril: A chronotherapeutic approach. Eur Rev Med Pharmacol Sci 1999; 3 (6): 269-275.
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