スラミンヘキサナトリウム 化学特性,用途語,生産方法
外観
白色～うすい黄色, 結晶性粉末～粉末
溶解性
水に溶ける。
効能
抗悪性腫瘍薬, 抗原虫薬
説明
Introduced into therapy for the treatment of early trypanosomiasis in the 1920s, suramin, a
bis-hexasulfonatednaphthylurea, is still considered to be the drug of choice for treatment of
non-CNS-associated African trypanosomiasis.
化学的特性
White crystalline powder
使用
Suramin sodium is a compound with a dyelike structure. Suramin is most effective against T. b. rhodesiense, but has also been used against T. b. gambiense infection. The compound causes side effects such as nausea, photophobia, and peripheral neuropathy which disappear shortly after conclusion of administration. Because the drug is unable to pass the bloodbrain barrier, prompt treatment of patients is essential. Suramin in combination with tryparsamide is an alternative that has been investigated.
適応症
Suramin (Germanin) is a derivative of a nonmetallic
dye whose antiparasitic mechanism of action is not
clear. It appears to act on parasite specificα-glycerophosphate
oxidase, thymidylate synthetase, dihydrofolate
reductase, and protein kinase but not on host enzymes.
抗菌性
Suramin has no significant trypanocidal activity in vitro, but
is effective in animals infected with T. brucei. Trypanosomes
take up suramin bound to plasma protein by a combination
of fluid phase and receptor-mediated endocytosis. It acts
synergistically with nitroimidazoles and eflornithine in the
elimination of trypanosomes from CSF of infected mice.
獲得抵抗性
Relapse rates of 30–50% have been recorded in Kenya and
Tanzania but there is no evidence of resistant parasites. Stable
resistance has been described in the related camel parasite
Trypanosoma evansi.
応用例（製薬）
A complex symmetrical molecule originally developed in
Germany in the early 1920s for the treatment of African trypanosomiasis.
Its useful anthelmintic activity is restricted to
O. volvulus and it has been used to achieve a radical cure of
onchocerciasis by killing the adult worms. However, it is an
extremely toxic drug and its use has become increasingly
uncommon since ivermectin became available.
生物活性
Non-selective P2 purinergic antagonist. Also blocks calmodulin binding to recognition sites and G protein coupling to G protein-coupled receptors. Anticancer and antiviral agent.
作用機序
Suramin is not absorbed from the intestinal tract
and is administered intravenously. Although the initial
high plasma levels drop rapidly, suramin binds tightly to
and is slowly released from plasma proteins, and so it
persists in the host for up to 3 months. Suramin neither
penetrates red blood cells nor enters the CNS. It is
taken up by the reticuloendothelial cells and accumulates
in the Kupffer cells of the liver and in the epithelial
cells of the proximal convoluted tubules of the kidney.
It is excreted by glomerular filtration, largely as the
intact molecule.
薬物動態学
Oral absorption: Poor
C
max 1 g intravenous doses (6 doses
at weekly intervals):
100 mg/L
Plasma half-life: 44–54 days
Volume of distribution: 20–80 L
Plasma protein binding: >99%
It is normally administered by slow intravenous infusion. It can
be detected in blood for 3 months; plasma levels >100 mg/L
were observed for several weeks after a 6-week course of treatment.
No metabolism was observed and 80% was removed
by renal clearance. Distribution to mononuclear phagocytes,
especially liver macrophages, the adrenal glands and the kidney
is high. It does not enter erythrocytes and penetrates the
blood–brain barrier poorly.
臨床応用
Suramin sodium is a high molecular-weight bisurea derivative containing six sulfonic acid groups as their sodium salts. It was developed in Germany shortly after World War I as a byproduct of research efforts directed toward the development of potential antiparasitic agents from dyestuffs. The drug has been used for more than half a century for the treatment of early cases of trypanosomiasis. Not until several decades later, however, was suramin discovered to be a long-term prophylactic agent whose effectiveness after a single intravenous injection is maintained for up to 3 months. The drug is tightly bound to plasma proteins, causing its excretion in the urine to be almost negligible. Tissue penetration of the drug does not occur, apparently because of its high molecular weight and highly ionic character. Thus, an injected dose remains in the plasma for a very long period. Newer, more effective drugs are now available for short-term treatment and prophylaxis of African sleeping sickness. Suramin is also used for prophylaxis of onchocerciasis. It is available from the CDC.
副作用
Suramin is toxic, especially in malnourished patients. A test
dose of 200 mg has been recommended. Immediate febrile
reactions (nausea, vomiting, loss of consciousness) can be
avoided by slow intravenous administration. Intramuscular or
subcutaneous injections are painful and irritating, and can be
followed by fever and urticaria. Anaphylactic shock occurs in
fewer than 1 in 2000 patients. Delayed reactions include renal
damage, exfoliative dermatitis, anemia, leukopenia, agranulocytosis,
jaundice and diarrhea.
スラミンヘキサナトリウム 上流と下流の製品情報
原材料
準備製品