ACE inhibitors are rapidly absorbed with maximum bioavailability being reached within 30 minutes to 7 hours depending on the specific ACE inhibitor and dose. Elimination half-life ranges from between one to 12 hours. 1-14
Table 1: ACE inhibitor maximum bioavailability and elimination half-life1-14
|
ACE Inhibitor
|
Tmax (h)
|
t1/2 (h)
|
|
Benazepril (Lotensin)
|
0.5-1
|
10-11
|
|
Captopril (Capoten*)
|
1
|
<2
|
|
Enalapril oral solution (Epaned)
|
4-6
|
11
|
|
Enalapril (Vasotec)
|
1
|
11
|
|
Enalaprilat injection (Vasotec injection*)
|
1-4
|
11
|
|
Fosinopril (Monopril*)
|
3
|
12
|
|
Lisinopril oral solution (Qbrelis)
|
6
|
12
|
|
Lisinopril (Prinivil*, Zestril)
|
6
|
12
|
|
Moexipril (Univasc*)
|
1.5
|
12
|
|
Perindopril (Aceon*)
|
3-7
|
1
|
|
Quinapril (Accupril)
|
2
|
3
|
|
Ramipril (Altace)
|
1
|
2-4
|
|
Trandolapril (Mavik*)
|
1
|
6
|
*Brand names with asterisks beside them have been discontinued in the US. The generic versions of these drugs continue to be FDA approved and are available in the US.
Most angiotensin-converting enzyme (ACE) inhibitors can be taken with or without food and so can be taken at any time throughout the day, including benazepril, enalapril, enalaprilat, fosinopril, lisinopril, perindopril, quinapril, ramipril, and trandolapril.1,3-9,11-14
The presence of food in the gastrointestinal tract reduces absorption of captopril by about 30-40% and moexipril by 40-50%. Manufacturers recommend administering one hour before meals to maximize bioavailability.2,10
A 2011 meta-analysis reviewed five randomized controlled trials which compared the relation between efficacy and time of administration (morning or evening) of an ACE inhibitor in patients with hypertension. Analysis of mean difference in 24-hour blood pressure found no statistically significant differences between evening versus morning dose administration.15
Studies with small sample sizes that compared the 24-hour antihypertensive effects of morning versus evening dose regimens have had conflicting conclusions. Some suggest that morning administration is preferable as it covers the whole 24 hours better than an evening dose.16-18 Others found an evening dose regimen had a better antihypertensive effect throughout a 24-hour period.19-21 Some studies comparing patients taking morning versus evening doses of long-acting ACE inhibitors did not find statistically significant differences in systolic blood pressure.23-24
References
- Lotensin [package insert]. Parsippany, NJ: Validus Pharmaceuticals LLC; 2019.
- Capoten [package insert]. Chestnut Ridge, NY: Par Pharmaceutical; 2017.
- Epaned [package insert]. Wilmington, MA: Azurity Pharmaceuticals, Inc.; 2020.
- Vasotec [package insert]. Bridgewater, NJ: Bausch Health US LLC; 2018.
- Enalaprilat [package insert]. Lake Forest, IL: Hospira, Inc.; 2021.
- Monopril [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2003.
- Qbrelis [package insert]. Wilmington, MA: Azurity Pharmaceuticals, Inc.; 2020.
- Prinivil [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2021.
- Zestril [package insert]. Morristown, NJ: Almatica Pharma LLC; 2020.
- Univasc [package insert]. Smyrna, GA: USB, Inc; 2012.
- Aceon [package insert]. Cincinnati, OH: Patheon Pharmaceuticals, Inc.; 2017.
- Accupril [package insert]. New York, NY: Parke Davis, Pfizer; 2021.
- Altace [package insert]. New York, NY: Pfizer Laboratories; 2022.
- Mavik [package insert]. Whippany, NJ: Halo Pharmaceutical Inc.; 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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