What is the pharmacokinetic profile of Lisinopril (Zestril), including its half-life and typical dosing regimen?

From the Guidelines

Lisinopril has a half-life of approximately 12 hours, allowing for once-daily dosing. The pharmacokinetic profile of Lisinopril (Zestril) is characterized by slow absorption, minimal protein binding, and renal elimination.

• The typical starting dose for hypertension is 10 mg once daily, which can be titrated up to 20-40 mg daily based on blood pressure response 1.
• For heart failure, dosing usually starts lower at 2.5-5 mg daily, with gradual increases as tolerated 1.
• For post-myocardial infarction, treatment typically begins with 5 mg within 24 hours of the event, followed by 5 mg after 24 hours, 10 mg after 48 hours, and then 10 mg daily maintenance. Lisinopril is not metabolized by the liver but is eliminated unchanged through the kidneys, so dosage adjustments are necessary in patients with renal impairment 1.
• The drug reaches peak plasma concentrations in about 7 hours, with steady-state levels achieved after 3-5 days of consistent dosing. Unlike some other ACE inhibitors, lisinopril does not require conversion to an active metabolite, as it is administered in its active form, contributing to its predictable dose-response relationship. The most recent guidelines from 2022 support the use of lisinopril in the management of heart failure, with a recommended initial daily dose of 2.5-5 mg once daily and a target dose of 20-40 mg once daily 1.

From the FDA Drug Label

Upon multiple dosing, lisinopril exhibits an effective half-life of 12 hours. The half-life of Lisinopril is 12 hours.

• The typical dosing regimen is once daily, as the antihypertensive effect is maintained during long-term therapy 2.
• Peak serum concentrations of lisinopril occur within about 7 hours after oral administration.
• Food does not alter the bioavailability of lisinopril.

From the Research

Pharmacokinetic Profile of Lisinopril

• Lisinopril is an orally active angiotensin-converting enzyme (ACE) inhibitor with a pharmacokinetic profile that allows for once-daily dosing 3, 4.
• After oral administration, 25-29% of the dose is absorbed intact, and biotransformation is not required for pharmacological activity 3.
• The onset of action occurs one to two hours after administration, with effects still present 24 hours later 3.
• The major route of elimination is through renal excretion, and an elimination half-life of 12.6 hours has been reported in normotensive individuals 3.

Half-Life and Renal Function

• In patients with impaired renal function (creatinine clearance less than or equal to 30 ml/min), a longer half-life and accumulation of lisinopril have been observed 3.
• The half-life of lisinopril is affected by renal function, and dose adjustments may be necessary in patients with renal impairment 3, 5.

Typical Dosing Regimen

• Lisinopril is typically administered in doses of 20-80 mg once daily for the treatment of essential hypertension 3, 4.
• In patients with congestive heart failure, doses of 2.5-20 mg once daily have been shown to be effective 3, 4.
• High doses of lisinopril (32.5-35 mg once daily) have been shown to be more effective than low doses (2.5-5 mg once daily) in reducing the risk of major clinical events in patients with heart failure 5.