PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
losartan

2D structure

Overview

Trade Names: Cozaar; DUP 89; Hyzaar; Lacidipine; Lortaan
PharmGKB Accession Id: PA450268

Description

An antagonist of angiotensin type 1 receptor with antihypertensive activity due to the reduced pressor effect of angiotensin II. PubChem (source: Drug Bank)

Indication

For the treatment of hypertension. (source: Drug Bank)

ATC Therapeutic Category

  • C09CA:Angiotensin II antagonists, plain

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Losartan and its longer acting active metabolite (E-3174) interfere with the binding of angiotensin II to the angiotensin II AT<sub>1</sub>-receptor by, themselves, binding reversibly to the receptors in vascular smooth muscle and the adrenal gland. As angiotensin II is a vasoconstrictor, which also stimulates the synthesis and release of aldosterone, blockage of its effects results in decreases in systemic vascular resistance. Neither Losartan or its metabolite inhibit the angiotensin converting enzyme, other hormone receptors, or ion channels. (source: Drug Bank)

Pharmacology

Losartan is the first of a class of antihypertensive agents called angiotensin II (AG II) receptor antagonists. It is, along with its longer acting active metabolite (E-3174), a specific and selective AT1 receptor antagonist. Losartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues, (e.g., vascular smooth muscle, adrenal gland). (source: Drug Bank)

Food Interactions

Take without regard to meals. Take at same time each day. Food delays absorption, but does not affect the extent of absorption. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. Oxidation of the 5-hydroxymethyl group on the imidazole ring results in the active metabolite of losartan. (source: Drug Bank)

Protein Binding

99.7% (source: Drug Bank)

Absorption

Well absorbed, the systemic bioavailability of losartan is approximately 33% (source: Drug Bank)

Toxicity

Hypotension and tachycardia; Bradycardia could occur from parasympathetic (vagal) stimulation, LD<sub>50</sub>= 1000 mg/kg (orally in rat) (source: Drug Bank)

Isomeric SMILES Code:

CCCCc1nc(c(n1Cc2ccc(cc2)c3ccccc3c4[nH]nnn4)CO)Cl (source: Drug Bank)

Curated Annotations (Curated Annotation)

  1. rs699 at chr1:228912417 in AGT
    Angiotensinogen polymorphism AGT:Met235Thr was not related to the response to antihypertensives in the SILVHIA study of 86 white hypertensive patients.
    Variant Name:
    AGT:Met235Thr, angiotensinogen M235T
    Related Drugs:
    atenolol, losartan
    Evidence:
    PMID:11593098
  2. rs4762 at chr1:228912600 in AGT
    Angiotensinogen polymorphism AGT:Thr174Met was not related to the response to antihypertensives in the SILVHIA study of 86 white hypertensive patients.
    Variant Name:
    AGT:Thr174Met; angiotensinogen T174M
    Related Drugs:
    atenolol, losartan
    Evidence:
    PMID:11593098
  3. rs5186 at chr3:149942678 in AGTR1
    Angiotensin II type 1 receptor polymorphism AGTR1:1166A>C was not related to the response to antihypertensives in the SILVHIA study of 86 white hypertensive patients.
    Variant Name:
    AGTR1:1166A>C, angiotensin II type 1 receptor A1166C
    Related Drugs:
    atenolol, losartan
    Evidence:
    PMID:11593098
  4. rs1057910 at chr10:96731043 in CYP2C9
    This variant (I359L) in exon 7 is part of the CYP2C9*3 allele. The residue 359 is located in the CYP2C9 active site. In vitro studies showed that the rate of losartan oxidation was lower in liver microsomes from individuals carring the CYP2C9*3 allele. This is consitant with an in vivo study showing that the CYP2C9*3 allele is associated with decreased formation of E-3174 (a more potent, active metabolite of losartan) in subjects given a single dose of losartan.
    Variant Name:
    CYP2C9: I359L; CYP2C9*3
    Related Drugs:
    losartan
    Evidence:
    PMID:11408373
    PMID:11823761
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Has annotations
ABCB1
  •   
  •   
  • PK
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
ACE
  •   
  •   
  •   
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
AGT
  •   
  •   
  •   
  •   
  •   
Variants
Phenotype data available Genotype Data Available Literature annotations available Not annotated
AGTR1
  •   
  • PD
  • PK
  • FA
  • GN
Publications, Variants
No phenotype data Genotype Data Available Literature annotations available Not annotated
CYP1A2
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C19
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
CYP2C8
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C9
  • CO
  • PD
  • PK
  • FA
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
CYP3A
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A5
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
SLC22A11
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
SLC22A9
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
TGFB1
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
UGT1A1
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
UGT1A3
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
UGT2B7
  •   
  •   
  • PK
  •   
  •   
Publications

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
AGTR1 Uncurated Annotation (source: Drug Bank)

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
amodiaquine
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
fluconazole
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
fluorouracil
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
fluvastatin
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
phenytoin
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
rifampin
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
valproic acid
  •   
  •   
  • PK
  •   
  •   
Publications

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug Description
amiloride Uncurated Annotation Increased risk of hyperkaliemia (source: Drug Bank)
drospirenone Uncurated Annotation Increased risk of hyperkaliemia (source: Drug Bank)
indomethacin Uncurated Annotation Indomethacin decreases the effect of losartan (source: Drug Bank)
lithium Uncurated Annotation Losartan increases serum levels of lithium (source: Drug Bank)
potassium Uncurated Annotation Increased risk of hyperkaliemia (source: Drug Bank)
rifampin Uncurated Annotation Rifampin decreases the effect of losartan (source: Drug Bank)
spironolactone Uncurated Annotation Increased risk of hyperkaliemia (source: Drug Bank)
triamterene Uncurated Annotation Increased risk of hyperkaliemia (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Breast Neoplasms
  • CO
  • PD
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Cardiomyopathies
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Cough
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Diabetes Mellitus
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Diabetes Mellitus, Type 2
  • CO
  •   
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Diabetic Nephropathies
  • CO
  •   
  •   
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Hypertension
  •   
  •   
  • PK
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Marfan Syndrome
  • CO
  •   
  •   
  •   
  • GN
Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

  1. Physicochemical determinants of human renal clearance

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00678
ChEBI ID:
6541
KEGG Compound ID:
C07072
PubChem Compound ID:
3961
PubChem Substance ID:
205151
IUPHAR Ligand ID:
590

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.

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