Lisinopril

Absorption

Lisinopril is 6-60% orally bioavailable with an average of 25% bioavailability. Lisinopril reaches a Cmax of 58ng/mL with a Tmax of 6-8h. Lisinopril's absorption is not affected by food.

Toxicity

The oral and subcutaneous LD50 in rats is >8500mg/kg and in mice is >9100mg/kg. The oral LDLO in women is 1200μg/kg/16D and in men is 43mg/kg/43W.
Patients experiencing an overdose of lisinopril may present with hypotension. Patients should be treated with intravenous saline to restore blood pressure. Lisinopril can be removed from the blood by hemodialysis due to it not being protein bound.

Description

Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor (IC₅₀ = 1.2 nM). It reduces the formation of endothelin-1 and increases nitric oxide (NO) in human vascular endothelial cells when used at a concentration of 0.1 nM. Lisinopril inhibits the pressor response to angiotensin I in anesthetized rats and dogs (ID₅₀s = 2.3 and 6.5 μg/kg, respectively).

Originator

Acebitor 5,Biddle Sawyer,India

The Uses of Lisinopril

Labeled Lisinopril, intended for use as an internal standard for the quantification fo Lisinopril by GC- or LC-mass spectrometry.

The Uses of Lisinopril

Lisinopril is an antihypertensive medication.

Indications

Lisinopril is indicated for the treatment of acute myocardial infarction, hypertension in patients ≥6 years, and as an adjunct therapy for heart failure. A combination product with hydrochlorothiazide is indicated for the treatment of hypertension.

Background

Lisinopril is an angiotensin converting enzyme inhibitor (ACEI) used to treat hypertension, heart failure, and myocardial infarction. Lisinopril and captopril are the only ACEIs that are not prodrugs. It functions by inhibition of angiotensin converting enzyme as well as the renin angiotensin aldosterone system. ACEIs are commonly used as a first line therapy in the treatment of hypertension, along with thiazide diuretics or beta blockers.
Lisinopril was granted FDA approval on 29 December 1987.

What are the applications of Application

Lisinopril is an angiotensin-converting enzyme (ACE)Inhibitor

Definition

ChEBI: Lisinopril is a dipeptide. It has a role as an EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor. It contains a L-prolino group and a L-lysine residue.

Manufacturing Process

2-Oxo-4-phenylbutyric acid and t-BOC-L-lysyl-L-proline are condensed in the presence of sodium cyanoborohydride. Essentially all of the t-BOC protecting group is cleaved when the product is absorbed on strong acid ion exchange resin. The crude N-(1-carboxy-3-phenylpropyl)-L-lysyl-L-proline is eluted from the resin with 10% ammonia, freeze dried, and purified by gel filtration chromatography (LH-20). A minute peak for t-BOC protons in the NMR spectrum disappears when the product is treated with ethyl acetate that is 4 N in hydrogen chloride gas. The NMR spectrum of the resulting HCl salt of the product is consistent with structure. The mass spectrum shows a molecular ion at 693 m/e for the tetrasilylated species. Chromatography on XAD-2 resin using 3.5% acetonitrile in 0.1 molar ammonium hydroxide affords N-α-((1S)- 1-carboxy-3-phenylpropyl)-L-lysyl-L-proline. The last peptide can be produced if 2-oxo-4-phenylbutyric acid and N-t-Boc-L-lysyl-L-proline are condensed in the presence of sodium cyanoborohydride. The product is absorbed on strong acid ion exchange resin, and eluted with 2% pyridine in water. Product-rich cuts are stripped to a glass and treated with 4 N HCl in ethylacetate to remove the t-Boc protecting group. The resulting hydrochloride salt is converted to the free base by absorbing on strong acid ion exchange resin and eluting with 2% pyridine in water. Freeze drying of product-rich cuts affords N-α-(1-carboxy-3-phenylpropyl)-L-lysyl-L-proline as a white fluffy solid. The NMR spectrum is consistent with structure. The mass spectrum shows a molecular ion at 549 for the disilylated species. Chromatography affords the desired isomer.

brand name

Prinivil (Merck); Zestril (AstraZeneca).

Therapeutic Function

Antihypertensive

Pharmacokinetics

Lisinopril is an angiotensin converting enzyme inhibitor used to treat hypertension, heart failure, and myocardial infarction. Lisinopril is not a prodrug, and functions by inhibition of angiotensin converting enzyme as well as the renin angiotensin aldosterone system. It has a wide therapeutic index and a long duration of action as patients are generally given 10-80mg daily.

Metabolism

Lisinopril is not metabolized and is excreted as the unchanged drug.