Telmisartan/ja

Telmisartan/ja

Clinical data
Pronunciation	/tɛlmɪˈsɑːrtən/
Trade names	ミカルディス, アクタビス, その他
AHFS/Drugs.com	Monograph
MedlinePlus	a601249
License data	US DailyMed: Telmisartan
Pregnancy category	AU: D
Routes of administration	By mouth
Drug class	Angiotensin II receptor antagonist/ja
ATC code	C09CA07 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only EU: RX-only
Pharmacokinetic data
Bioavailability	42–100%
Protein binding	>99.5%
Metabolism	最小限の肝臓（グルクロン酸化）
Elimination half-life	24時間
Excretion	糞中97%
Identifiers
IUPAC name 2-(4-{[4-Methyl-6-(1-methyl-1H-1,3-benzodiazol-2-yl)-2-propyl-1H-1,3-benzodiazol-1-yl]methyl}phenyl)benzoic acid
CAS Number	144701-48-4 Y
PubChem CID	65999
IUPHAR/BPS	592
DrugBank	DB00966 Y
ChemSpider	59391 Y
UNII	U5SYW473RQ
KEGG	D00627 Y
ChEBI	CHEBI:9434 Y
ChEMBL	ChEMBL1017 Y
Chemical and physical data
Formula	C33H30N4O2
Molar mass	514.629 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C(O)c1ccccc1c2ccc(cc2)Cn3c4cc(cc(c4nc3CCC)C)c5nc6ccccc6n5C
InChI InChI=1S/C33H30N4O2/c1-4-9-30-35-31-21(2)18-24(32-34-27-12-7-8-13-28(27)36(32)3)19-29(31)37(30)20-22-14-16-23(17-15-22)25-10-5-6-11-26(25)33(38)39/h5-8,10-19H,4,9,20H2,1-3H3,(H,38,39) Y Key:RMMXLENWKUUMAY-UHFFFAOYSA-N Y
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テルミサルタン（Telmisartan）は、とりわけ、ミカルディスという商品名で販売されており、高血圧、心不全、糖尿病性腎臓病の治療に用いられる医薬品である。高血圧の初期治療として妥当である。経口で服用する。 テルミサルタン/ヒドロクロロチアジド配合剤、テルミサルタン/シルニジピン配合剤、テルミサルタン/アムロジピン配合剤がある。

一般的な副作用には、上気道感染症、下痢、背部痛などがある。重篤な副作用としては、腎障害、低血圧、血管浮腫などがある。妊娠中の使用は赤ちゃんに害を及ぼす可能性があり、授乳中の使用は推奨されない。アンジオテンシンII受容体拮抗薬であり、アンジオテンシンIIの作用を阻害することで作用する。

テルミサルタンは1991年に特許を取得し、1999年に医薬品として使用されるようになった。ジェネリック医薬品として販売されている。2021年には、1 万件以上の処方で、米国で217番目に多く処方された医薬品であった。

Medical uses

Telmisartan is used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure.

Contraindications

Telmisartan is contraindicated during pregnancy. Like other drugs affecting the renin–angiotensin system (RAS), telmisartan can cause birth defects, stillbirths, and neonatal deaths. It is not known whether the drug passes into the breast milk. Also it is contraindicated in bilateral renal artery stenosis in which it can cause kidney failure.

Side effects

Side effects are similar to other angiotensin II receptor antagonists and include tachycardia and bradycardia (fast or slow heartbeat), hypotension (low blood pressure) and edema (swelling of arms, legs, lips, tongue, or throat, the latter leading to breathing problems). Allergic reactions may also occur.

Interactions

Due to its mechanism of action, telmisartan increases blood potassium levels. Combination with potassium preparations or potassium-sparing diuretics could cause hyperkalaemia (excessive potassium levels). Combination with NSAIDs, especially in patients with impaired kidney function, has a risk of causing (usually reversible) kidney failure.

Pharmacology

Mechanism of action

Telmisartan is an angiotensin II receptor blocker that shows high affinity for the angiotensin II receptor type 1 (AT₁), with a binding affinity 3000 times greater for AT₁ than AT₂.

In addition to blocking the renin–angiotensin system, telmisartan acts as a selective modulator of peroxisome proliferator-activated receptor gamma (PPAR-γ), a central regulator of insulin and glucose metabolism. It is believed that telmisartan's dual mode of action may provide protective benefits against the vascular and renal damage caused by diabetes and cardiovascular disease (CVD).

Telmisartan's activity at the peroxisome proliferator-activated receptor delta (PPAR-δ) receptor has prompted speculation around its potential as a sport doping agent as an alternative to GW 501516. Telmisartan activates PPAR-δ receptors in several tissues.

Also, telmisartan has a PPAR-γ agonist activity.

Pharmacokinetics

The substance is quickly but to varying degrees absorbed from the gut. The average bioavailability is about 50% (42–100%). Food intake has no clinically relevant influence on the kinetics of telmisartan. Plasma protein binding is over 99.5%, mainly to albumin and alpha-1-acid glycoprotein. It has the longest half-life of any angiotensin II receptor blocker (ARB) (24 hours) and the largest volume of distribution among ARBs (500 liters). Less than 3% of telmisartan is inactivated by glucuronidation in the liver, and over 97% is eliminated in unchanged form via bile and faeces.

History

See also: Discovery and development of angiotensin receptor blockers

Society and culture

Telmisartan is available as a generic medication.

Further reading

• Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, et al. (April 2008). "Telmisartan, ramipril, or both in patients at high risk for vascular events". The New England Journal of Medicine. Massachusetts Medical Society. 358 (15): 1547–59. doi:10.1056/nejmoa0801317. hdl:2437/81925. PMID 18378520.
• Yusuf S, Teo K, Anderson C, Pogue J, Dyal L, Copland I, et al. (September 2008). "Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial". Lancet. 372 (9644): 1174–83. doi:10.1016/S0140-6736(08)61242-8. PMID 18757085. S2CID 5203511. Retrieved 26 November 2019.