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a drug (trade name Purinethol) that interferes with the metabolism of purine and is used to treat acute lymphocytic leukemia (同)Purinethol

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/10/22 01:10:39」(JST)

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Mercaptopurine (also called 6-mercaptopurine, 6-MP or its brand name Purinethol) is an immunosuppressive drug.

It is a thiopurine.^[1]

Uses

It is used to treat leukemia, pediatric non-Hodgkin's lymphoma,^{[citation needed]} polycythemia vera,^[2] psoriatic arthritis,^[3] and inflammatory bowel disease (such as Crohn's disease and ulcerative colitis).^[4]

It has demonstrated some in vitro effectiveness against Mycobacterium paratuberculosis.^[5]

Mechanisms of action

6-MP ribonucleotide inhibits purine nucleotide synthesis and metabolism. This alters the synthesis and function of RNA and DNA. Mercaptopurine interferes with nucleotide interconversion and glycoprotein synthesis.

Adverse reactions

Some of the adverse reactions of taking mercaptopurine might include diarrhea, nausea, vomiting, loss of appetite, fatigue, stomach/abdominal pain, weakness, skin rash, darkening of the skin, or hair loss. Serious adverse reactions include mouth sores, fever, sore throat, easy bruising or bleeding, pinpoint red spots on the skin, yellowing of eyes or skin, dark urine, and painful or difficult urination. Unlikely but serious side effects include: black or tarry stools (melena), bloody stools, and bloody urine.

Symptoms of allergic reaction to mercaptopurine include rash, itching, swelling, dizziness, trouble breathing, and pancreatitis.

Mercaptopurine causes myelosuppression, suppressing the production of white blood cells and red blood cells. It may be toxic to bone marrow. Weekly blood counts are recommended for patients on mercaptopurine. The patient should stop taking the medication at least temporarily if there is an unexplained, abnormally large drop in white blood cell count, or any other blood count.

Patients exhibiting myelosuppression or bone marrow toxicity should be tested for thiopurine methyltransferase (TPMT) enzyme deficiency. Patients with TPMT deficiency are much more likely to develop dangerous myelosuppression.^[6] In such patients, it may be possible to continue using mercaptopurine, but at a lower dose.

Drug interactions

Allopurinol inhibits xanthine oxidase, the enzyme that breaks down mercaptopurine. Those taking allopurinol (often used to prevent gout) are at risk for mercaptopurine toxicity. The dose should be reduced or allopurinol should be discontinued.

Precautions

Mercaptopurine can lower the body's ability to fight off infection. Those taking it should get permission from a doctor to receive immunizations and vaccinations. It is also recommended that, while on the drug, one should avoid those having recently received oral polio vaccine.

This drug is traditionally not recommended during pregnancy and current evidence indicates pregnant women on the drug (or the related azathioprine) show a seven-fold incidence of fetal abnormalities as well as a 20-fold increase in miscarriage.^[7] Davis et al. 1999 found mercaptopurine, compared to methotrexate, was ineffective as a single-agent abortifacient; every woman in the mercaptopurine arm of the study had fetal cardiac activity at follow-up (two weeks later) and was given a suction abortion.^[8]

Mercaptopurine causes changes to chromosomes in animals and humans, though a study in 1990^[9] found, "while the carcinogenic potential of 6-MP cannot be precluded, it can be only very weak or marginal." Another study in 1999^[10] noted an increased risk of developing leukemia when taking large doses of 6-MP with other cytotoxic drugs.

References

^ Sahasranaman, S.; Howard, D.; Roy, S. (2008). "Clinical pharmacology and pharmacogenetics of thiopurines". European Journal of Clinical Pharmacology 64 (8): 753–767. doi:10.1007/s00228-008-0478-6. PMID 18506437.
^ Shullenberger, C. C. (1962). "Long-rangetreatment of polycythemia vera with 6-mercaptopurine". Cancer chemotherapy reports. Part 1 16: 251–252. PMID 13912387. edit
^ Baum, J.; Hurd, E.; Lewis, D.; Ferguson, J. L.; Ziff, M. (1973). "Treatment of psoriatic arthritis with 6-mercaptopurine". Arthritis & Rheumatism 16 (2): 139. doi:10.1002/art.1780160202. edit
^ Nielsen OH, Vainer B, Rask-Madsen J (November 2001). "Review article: the treatment of inflammatory bowel disease with 6-mercaptopurine or azathioprine". Aliment. Pharmacol. Ther. 15 (11): 1699–708. doi:10.1046/j.1365-2036.2001.01102.x. PMID 11683683. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0269-2813&date=2001&volume=15&issue=11&spage=1699.
^ Shin SJ, Collins MT (February 2008). "Thiopurine drugs azathioprine and 6-mercaptopurine inhibit Mycobacterium paratuberculosis growth in vitro". Antimicrob. Agents Chemother. 52 (2): 418–26. doi:10.1128/AAC.00678-07. PMC 2224720. PMID 18070971. http://aac.asm.org/cgi/pmidlookup?view=long&pmid=18070971.
^ Yates, C. R.; Krynetski, E. Y.; Loennechen, T.; Fessing, M. Y.; Tai, H. L.; Pui, C. H.; Relling, M. V.; Evans, W. E. (1997). "Molecular diagnosis of thiopurine S-methyltransferase deficiency: Genetic basis for azathioprine and mercaptopurine intolerance". Annals of internal medicine 126 (8): 608–614. PMID 9103127.
^ Nørgård, B.; L. Pedersen, K. Fonager, S. Rasmussen, H. Sørensen (March 2003). "Azathioprine, mercaptopurine and birth outcome: a population-based cohort study". Alimentary pharmacology and therapeutics 17 (6): 827–834. doi:10.1046/j.1365-2036.2003.01537.x. PMID 12641505.
^ Davis, Anne R.; Leslie Miller, Hisham Tamimi, and Allen Gown (June 1999). "Methotrexate Compared With Mercaptopurine for Early Induced Abortion". Obstetrics & Gynecology 93 (6): 904–9. doi:10.1016/S0029-7844(98)00569-9. PMID 10362152. http://www.greenjournal.org/cgi/content/full/93/6/904.
^ Maekawa, A.; T. Nagaoka, H. Onodera, Y. Matsushima, A. Todate, M. Shibutani, H. Ogasawara, Y. Kodama and Y. Hayashi (May 1990). "Two-year carcinogenicity study of 6-mercaptopurine in F344 rats". Journal of Cancer Research and Clinical Oncology 116 (3): 245–250. doi:10.1007/BF01612898. PMID 2370249. http://www.springerlink.com/content/k28hxj615p761764/.
^ Bo J, Schrøder H, Kristinsson J, Madsen B, Szumlanski C, Weinshilboum R, Andersen JB, Schmiegelow K (September 1999). "Possible carcinogenic effect of 6-mercaptopurine on bone marrow stem cells: relation to thiopurine metabolism". Cancer 86 (6): 1080–6. doi:10.1002/(SICI)1097-0142(19990915)86:6<1080::AID-CNCR26>3.0.CO;2-5. PMID 10491537.

External links

FDA Label, Mercaptopurine (PDF)

UpToDate Contents

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1. 6-メルカプトプリン（6-MP）またはアザチオプリンを用いた炎症性腸疾患治療における6-MP代謝産物モニタリングおよびTPMT検査 6 mercaptopurine 6 mp metabolite monitoring and tpmt testing in the treatment of inflammatory bowel disease with 6 mp or azathioprine
2. 炎症性腸疾患におけるアザチオプリンおよび6-メルカプトプリン azathioprine and 6 mercaptopurine in inflammatory bowel disease
3. 成人における抗癌剤の投与 dosing of anticancer agents in adults
4. 成人における重症または難治性クローン病の内科的マネージメントの概要 overview of the medical management of severe or refractory crohn disease in adults
5. 小児および思春期におけるクローン病マネージメントの概要 overview of the management of crohn disease in children and adolescents

English Journal

Combination therapy with arsenic trioxide, all-trans retinoic acid, and chemotherapy in acute promyelocytic leukemia patients with various relapse risks.

Huang H, Qin Y, Xu R, You X, Teng R, Yang L, Xu M, Liu H.SourceDepartment of Hematology, Nantong University Affiliated Hospital, Jiangsu, China.
Leukemia research.Leuk Res.2012 Jul;36(7):841-5. Epub 2012 Apr 23.
To improve the recovery rate of high-risk patients with acute promyelocytic leukemia (APL), we used all-trans retinoic acid (ATRA)/arsenic trioxide (ATO)/daunorubicin combination in remission induction, daunorubicin and cytarabine in consolidation, and ATRA/ATO/methotrexate±6-mercaptopurine in main
PMID 22534100

Infliximab Exerts No Direct Hepatotoxic Effect on HepG2 Cells In Vitro.

de Vries HS, de Heij T, Roelofs HM, Te Morsche RH, Peters WH, de Jong DJ.SourceDepartment of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands, h.devries@MDL.umcn.nl.
Digestive diseases and sciences.Dig Dis Sci.2012 Jun;57(6):1604-8. Epub 2012 Apr 26.
BACKGROUND: Infliximab-induced hepatotoxicity is reported in several case studies involving patients with inflammatory bowel disease (IBD) and a direct hepatotoxic effect has been proposed.OBJECTIVE: The aim of this study was to determine the direct in vitro toxicity of infliximab. As a proof of pri
PMID 22535279

Japanese Journal

Improvement in the Anticancer Activity of 6-Mercaptopurine via Combination with Bismuth(Ⅲ)

Chemical and pharmaceutical bulletin 64(11), 1539-1545, 2016-11
NAID 40020975407

白血病治療におけるpharmacogenomics (特集小児血液疾患における遺伝子変異の探索)

臨床血液 57(7), 910-918, 2016-07
NAID 40020923971

メルカプトプリンによる重度の血液毒性をきたしたNUDT15ホモバリアントを有する小児急性リンパ性白血病

臨床血液 57(6), 748-753, 2016
NAID 130005163318

Related Pictures

★リンクテーブル★

リンク元	「6-メルカプトプリン」「アザチオプリン」「6-MP」
拡張検索	「6-mercaptopurine riboside」
関連記事	「mercaptopurine」

「6-メルカプトプリン」

Mercaptopurine
Systematic (IUPAC) name
	3,7-dihydropurine-6-thione
Clinical data
Trade names	Purinethol
AHFS/Drugs.com	monograph
MedlinePlus	a682653
Pregnancy cat.	D
Legal status	℞ Prescription only
Routes	Oral
Pharmacokinetic data
Bioavailability	5 to 37%
Metabolism	xanthine oxidase
Half-life	60 to 120 min., longer for its active metabolites
Excretion	Renal
Identifiers
CAS number	50-44-2
ATC code	L01BB02
PubChem	CID 667490
DrugBank	DB01033
ChemSpider	580869
UNII	PKK6MUZ20G
KEGG	D04931
ChEBI	CHEBI:50667
ChEMBL	CHEMBL1425
Chemical data
Formula	C5H4N4S
Mol. mass	152.177 g/mol
	SMILES S=C2/N=C\Nc1ncnc12;
	InChI InChI=1S/C5H4N4S/c10-5-3-4(7-1-6-3)8-2-9-5/h1-2H,(H2,6,7,8,9,10) ; Key:GLVAUDGFNGKCSF-UHFFFAOYSA-N ;
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　　[★]

英: 6-mercaptopurine, mercaptopunne
ラ: 6-mercaptopurinum
同: 6-MP
商: ロイケリン
関: アザチオプリン、制癌薬

GOO. 134-138,1347f
プリン代謝拮抗薬
抗悪性腫瘍薬

白血病治療薬

プリンの6位にSが付加された物質。

代謝

投与された6-MPはPPRP(phosphoribosylpyrophosphateにより6-thioinosine 5'-monophosphate(TIMP)となる
6-thioinosine 5'-monophosphateはいくつかの代謝を経て6-thioguanosine 5'-monophosphate(TGN)となる

作用機序

TIMPがプリン塩基の生合成を阻害する

本剤は、細胞増殖に重要な意義をもつ核酸の生合成を阻害する。メルカプトプリンは細胞内でinosinic acidのチオ同族体 thioinosinic acid（TIMP）に変換し、このTIMPは主としてinosinic acid からのadenylosuccinic acid 及びxanthylic acidへの転換を阻害し、adenine, guanineribonucleotideの生合成を阻害するとされている