Losartan drug data and news

Losartan drug data, resources, and news articles (when available). Onconews.org provides news on cancer research. This section, which includes profiles on medicines that may or not be cancer-related is in beta form. If things run smoothly we will be releasing a new format late in the summer of 2006.

Generic name Losartan
Brand Names/Synonyms CHEMBANK1667; Cozaar; DUP 89; Hyzaar; Lacidipine; Lortaan; Losartan
Indication For the treatment of hypertension
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Description Not Available
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).
Mechanism Of Action Losartan and its longer acting active metabolite (E-3174) interfere with the binding of angiotensin II to the angiotensin II AT1-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.
Losartan News
(When available)

Merck profits edge ahead in fourth quarter  Feb 1, 2006
Merck's blood pressure treatment range, headed by Cozaar (losartan) and Hyzaar (losartan and hydrochlorothiazide), advanced 2% to $782 million in the fourth ... - Pharma Times (subscription),

Dosage Forms Tablets
Drug_Category Antihypertensive Agents; Antiarrhythmic Agents; Angiotensin II Receptor Antagonists; ATC:C09CA01
Absorption Well absorbed, the systemic bioavailability of losartan is approximately 33%
Interactions -->Interactions for Losartan:

No significant drug-drug pharmacokinetic interactions have been found in interaction studies with hydrochlorothiazide, digoxin, warfarin, cimetidine and phenobarbital. Rifampin, an inducer of drug metabolism, decreased the concentrations of losartan and its active metabolite. In humans, two inhibitors of P450 3A4 have been studied. Ketoconazole did not affect the conversion of losartan to the active metabolite after intravenous administration of losartan, and erythromycin had no clinically significant effect after oral administration. Fluconazole, an inhibitor of P450 2C9, decreased active metabolite concentration and increased losartan concentration. The pharmacodynamic consequences of concomitant use of losartan and inhibitors of P450 2C9 have not been examined. Subjects who do not metabolize losartan to active metabolite have been shown to have a specific, rare defect in cytochrome P450 2C9. These data suggest that the conversion of losartan to its active metabolite is mediated primarily by P450 2C9 and not P450 3A4.

As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium.

As with other antihypertensive agents, the antihypertensive effect of losartan may be blunted by the non-steroidal anti-inflammatory drug indomethacin.

 

Toxicity hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation, LD50= 1000 mg/kg(orally in rat)
Organisms Affected Humans and other mammals
Chemical IUPAC Name [2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]-3H-imidazol-4-yl]methanol
Chemical Formula C22H23ClN6O
Molecular Weight 422.911 g/mol
Smiles String CCCCC1=NC(=C(N1CC2=CC=C(C=C2)C3=CC=CC=C3C4=NNN=N4)CO)Cl
Melting Point 183.5-184.5 °C
Water Solubility 0.82 mg/L
State White to off-white free flowing crystalline powder
LogP/Hphobicity 5.438
Isoelectric Point Not Available
Biotransformation Hepatic. Oxidation of the 5-hydroxymethyl group on the imidazole ring results in the active metabolite of losartan.
Half Life 2 hours
Protein Binding [%] 99.70%
RxList Link RXlist
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Drug Reference http://www.drugs.com/cons/Losartan.html
http://www.rxlist.com/cgi/generic/losar.htm
Drug Type Approved Drug
Accession No APRD00052
CAS Registry Number 114798-26-4
KEGG Compound ID C07072
PubChem ID SID:205151
PharmGKB ID PA450268
SwissProt ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 2182882

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