デキサメタゾン

外観

白色～わずかにうすい黄色, 結晶～粉末

溶解性

エタノール及びアセトンにやや溶けにくく、水にほとんど溶けない。

解説

C22H29FO5(392.46)．1958年，G.E. Arthらにより16α-メチルヒドロコルチゾン=アセタートから合成された．ベタメタゾンの16位のメチルがα配位であることが異なるのみである．白色～微黄色の結晶．分解点約245 ℃．[α]²⁰_D＋72～＋80°(ジオキサン)．メタノール，エタノール，アセトンまたはジオキサンに微溶，水，エーテルに難溶．デキサメタゾンは，副じん皮質ホルモン作用，とくにグルココルチコイド作用が強い．ヒドロコルチゾンの25倍の抗炎症作用をもつ．リウマチ性関節炎，アレルギー性疾患，皮膚疾患，アレルギー性および炎症性眼疾患などの治療に用いられる．LD50 120 mg/kg(ラット，皮下)．森北出版「化学辞典（第2版）

用途

無血清培地添加剤、薬理研究用。

用途

副腎皮質ホルモン剤です。糖 質コルチコイドの 16β 位にメチル基が付加し ています。鉱質コルチコイド作用を弱めた性 質を有しています。

効能

抗炎症薬, 鎮痒薬, グルココルチコイド受容体作動薬

商品名

アフタゾロン (あゆみ製薬); デカドロン (日医工); デカドロン (日医工); レナデックス (セルジーン)

説明

The activity of dexamethasone, as measured by glycogen deposition, is 20 times greater than that of hydrocortisone. It has five times the anti-inflammatory activity of prednisolone. Clinical data indicate that this compound has seven times the antirheumatic potency of prednisolone. It is roughly 30 times more potent than hydrocortisone. Its pharmacokinetics are presented in Table 33.3. Routes of metabolism for dexamethasone are similar to those for prednisolone, with its primary 6β-hydroxy metabolite being recovered in urine. Dexamethasone sodium phosphate is the water-soluble sodium salt of the 21-phosphate ester, with an IV half-life of less than 10 minutes because of rapid hydrolysis by plasma phosphatases. Peak plasma levels for dexamethasone usually are attained in approximately 10 to 20 minutes following its IV administered dose. A similar reaction occurs when the phosphate ester is applied topically or by inhalation.

化学的特性

White or almost white, crystalline powder.

使用

Dexamethasone is used for the same indications as all corticosteroids; however, it exhibits a significantly more powerful anti-inflammatory and anti-allergic action. It is used for circulatory collapse—shock during or after surgical operations, trauma, blood loss, myocardial infarction, and burns. It is also used in severe infections—toxemia, vascular collapse in meningococcosis, septicemia, diphtheria, typhoid fever, and peritonitis. It is used in severe allergic conditions—asthmatic status, laryngeal edema, severe anaphylactic reactions to medicinal drugs, and pyrogenic reactions.

適応症

Cushing’s disease is defined as hypercortisolism due to chronic overproduction of corticotrophin by a corticotroph adenoma. Cortisol’s lack of suppressibility during the administration of low doses of dexamethasone but suppressibility during high-dose dexamethasone is the key diagnostic finding in 99% of the patients with Cushing’s disease. This contrasts with the lack of glucocorticoid suppressibility typically found in patients with corticotrophin-independent hypercortisolism (Cushing’s syndrome). A judicious selection of the available tests may be necessary to obtain an accurate diagnosis in patients with Cushing’s syndrome.

一般的な説明

Dexamethasone, 9-fluoro-11β,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione,is the 16 -isomer of betamethasone.
Dexamethasone acetate, USP (21-acetate)
Dexamethasone sodium phosphate, USP (21-sodiumphosphate).

空気と水の反応

Insoluble in water.

反応プロフィール

Dexamethasone may be sensitive to prolonged exposure to light. Dexamethasone is incompatible with strong oxidizers, strong acids, acid chlorides and acid anhydrides. Oxidation may occur with bases.

火災危険

Flash point data for Dexamethasone are not available; however, Dexamethasone is probably combustible.

生物活性

Glucocorticoid; anti-inflammatory. Reduces levels of activated NF- κ B in immature dendritic cells (DCs) and inhibits differentiation into mature DCs.

薬物動態学

The activity of dexamethasone, as measured by glycogen deposition, is 20 times greater than that of hydrocortisone. It has five times the anti-inflammatory activity of prednisolone. Clinical data indicate that this compound has seven times the antirheumatic potency of prednisolone. It is roughly 30 times more potent than hydrocortisone. Its pharmacokinetics are presented in Table 33.3. Routes of metabolism for dexamethasone are similar to those for prednisolone, with its primary 6β-hydroxy metabolite being recovered in urine. Dexamethasone sodium phosphate is the water-soluble sodium salt of the 21-phosphate ester, with an IV half-life of less than 10 minutes because of rapid hydrolysis by plasma phosphatases. Peak plasma levels for dexamethasone usually are attained in approximately 10 to 20 minutes following its IV administered dose. A similar reaction occurs when the phosphate ester is applied topically or by inhalation.

薬理学

Dexamethasone is a corticosteroid with high glucocorticoid activity and virtually no mineralocorticoid activity. I ts mechanism of action as an antiemetic is unknown, but it is possible that either direct genomic or indirect non-genomic effects on 5-HT3 and GABAA receptors contribute to its antiemetic activity. Many of the original studies were carried out using 8– 10mg of dexamethasone phosphate, but smaller doses (2.5–4mg) provide equal antiemetic efficacy with minimal risk of adverse effects. Concerns relating to adrenal suppression and other steroid-induced adverse effects (including increased risk of bleeding) after a single dose of dexamethasone remain largely unfounded. O ne of the most unpleasant adverse effects of dexamethasone involves intense perineal stimulation after rapid i.v. injection.

安全性プロファイル

Poison by intraperitoneal and subcutaneous routes. An experimental teratogen. Experimental reproductive effects. Mutation data reported. When heated to decomposition it emits toxic fumes of F-.

純化方法

Dexamethasone has been recrystallised from Et2O or small volumes of EtOAc. Its solubility in H2O is 10 mg/100mL at 25o; and is freely soluble in Me2CO, EtOH and CHCl3. [Arth et al. J Am Chem Soc 80 3161 1958; for the -methyl isomer see Taub et al. J Am Chem Soc 82 4025 1960, see Beilstein 8 IV 3501.]