Are short-acting or longer-acting ARBs preferred for hypertension? Are there ARBs that have similar pharmacokinetics to olmesartan (i.e., longer duration of action), and which ARBs have shorter half-lives compared to olmesartan?

Background

The pharmacokinetic characteristics of the angiotensin receptor blockers (ARBs) vary based on the discussion article but are similar enough to highlight certain properties of individual agents (see Table 1). Based on the most recent study reporting pharmacokinetic ARB parameters, olmesartan’s half-life ranges between 12 to 14 hours. This half-life is longer than losartan (4-6 h), eprosartan (5-7 h), and valsartan (7 h) but is similar to azilsartan (11 h), candesartan (9-13 h), and irbesartan (12-20 h). Telmisartan is the longest-acting ARB with a half-life of 24 hours. Whether a duration of action is associated with greater control of blood pressure has not been thoroughly investigated. ARBs with a longer duration of action may improve patient compliance by reducing the burden of dosing from BID to once daily in certain cases. However, one study comparing olmesartan versus losartan, valsartan, and irbesartan at recommended starting doses found a significant reduction in mean 24-hour diastolic blood pressure for olmesartan. The study authors hypothesize that olmesartan’s longer half-life may contribute to clinical efficacy while reducing the inconsistency between dosing intervals. However, two other studies that compared candesartan, losartan, and valsartan did not report a difference in blood pressure control. [1], [2], [3], [4]

Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

Are there other ARBs that have similar pharmacokinetics to olmesartan (i.e., longer duration of action) and which ARBs have shorter half-lives compared to olmesartan?

Please see Tables 1-2 for your response.

Pharmacokinetic properties of angiotensin receptor blockers (ARBs)
	Tmax, hours	Bioavailability	Half-life, hours
Candesartan	3.0 to 5.0	42%	9 to 13
Eprosartan	2.0 to 6.0	13%	5 to 7
Irbesartan	1.0 to 2.0	60% to 80%	12 to 20
Losartan	3.0 to 4.0	33%	4 to 6
Olmesartan	1.4 to 2.8	26%	11.8 to 14.7
Telmesartan	1.0	43%	24
Valsartan	2.0	23%	7
Azilsartan	1.5 to 3.0	60%	11

References:

Adapted from:
Gallo G, Volpe M, Rubattu S. Angiotensin Receptor Blockers in the Management of Hypertension: A Real-World Perspective and Current Recommendations. Vasc Health Risk Manag. 2022;18:507-515. Published 2022 Jul 11. doi:10.2147/VHRM.S337640

Efficacy and Tolerability of Olmesartan, Telmisartan, and Losartan in Patients of Stage I Hypertension: A Randomized, Open-label Study
Design	Randomized, open-label, parallel-group, comparative study N= 57
Objective	To compare the efficacy and tolerability of losartan, telmisartan, and olmesartan as antihypertensive agents
Study Groups	Olmesartan (n= 20) Telmisartan (n= 19) Losartan (n= 18)
Inclusion Criteria	Age > 18 years, newly diagnosed with stage I hypertension
Exclusion Criteria	Suffering from diabetes, abnormal liver or kidney function, any other systemic illness; taking other concomitant medication including antihypertensive medication; pregnancy/lactation
Methods	Patients were randomized to receive one of three medications: olmesartan tablet 20 mg PO once daily, telmisartan tablet 40 mg PO once daily, or losartan tablet 50 mg PO once daily. Patients were given two weeks' worth of tablets and followed up at 2-week intervals for 3 months.
Duration	Study enrollment period: January 2013 to September 2014 Follow-up: 3 months
Outcome Measures	Primary: change in sitting cuff diastolic blood pressure (DBP)
0.14 0.48		Olmesartan (n= 20)	Telmisartan (n= 19)	Losartan (n= 18)
	Age, years	46.2	48.26	49.94
	Female	7	7	6
	Diastolic BP, mmHg Systolic BP, mmHg	95.05 147.38	94.53 148.8	93.44 149.9
Results	Endpoint	Olmesartan (n= 20)	Telmisartan (n= 19)	Losartan (n= 18)
	Diastolic BP, mmHg 2 weeks 4 weeks 8 weeks 12 weeks	85.90* 84.86* 83.71* 81.24*	87.37* 86.32* 85.16* 82.53*	88.78* 87.33* 87.67* 86.11*
	Systolic BP, mmHg 2 weeks 4 weeks 8 weeks 12 weeks	136.5* 135.7* 133.2* 131.0*	140.4* 140.4* 138.6* 137.1*	143.0* 142.0* 141.4* 138.7*
	*p< 0.001 versus baseline
Adverse Events	Headache (n= 1 in the olmesartan group), dizziness (n= 1 in the telmisartan group) No serious adverse events reported
Study Author Conclusions	The most efficacious drug in reducing BP is Olmesartan whereas telmisartan and losartan show equal efficacy.
InpharmD Researcher Critique	Follow-up was limited to 3 months which may not represent long-term blood pressure management. Both telmisartan and olmesartan are characterized by a long half-life which the authors believe minimized the effects of missing or delaying medication dosing. However, adherence to the medication regimen was not measured.

References:

Kalikar M, Nivangune KS, Dakhale GN, Bajait CS, Sontakke SD, Motghare VM, Budania R. Efficacy and Tolerability of Olmesartan, Telmisartan, and Losartan in Patients of Stage I Hypertension: A Randomized, Open-label Study. J Pharmacol Pharmacother. 2017 Jul-Sep;8(3):106-111. doi: 10.4103/jpp.JPP_39_17