Effects of mercaptopurine: A Synthesis of Findings from 14 Studies

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Original Abstract of the Article

Major Research Findings

Mercaptopurine is a medication used to treat a variety of diseases, including inflammatory bowel disease, cancer, and to suppress the immune system after transplantation. studied the frequency and course of adverse effects of azathioprine/6-mercaptopurine treatment in patients with inflammatory bowel disease. compared the effects of DL-glyceraldehyde, 6-mercaptopurine, methotrexate, and 5-fluorouracil on the Ehrlich ascites carcinoma in vivo. 4 investigated the differential effects of targeted disruption of thiopurine methyltransferase on mercaptopurine and thioguanine pharmacodynamics. Mercaptopurine is also effective in treating leukemia, and 6 examined its effects on transmethylation during consolidation treatment of acute lymphoblastic leukemia. 9 explored the effects of mercaptopurine alone or in combination with methotrexate on de novo purine synthesis inhibition and antileukemic effects in vivo. focused on the effects of certain antimetabolites on the growth of a 6-mercaptopurine-resistant subline of the Ehrlich ascites carcinoma. 13 revealed the inhibitory effects of 6-thioguanine and 6-mercaptopurine on the USP2a target fatty acid synthase in human submaxillary carcinoma cells. 14 studied the effects of dose escalation on thioguanine nucleotide metabolites in children with leukemia. looked at the effects of 6-mercaptopurine treatment on fertility in patients with Crohn's disease. 7 found that mercaptopurine can have teratogenic effects on chick embryos. 10 investigated the effects of mercaptopurine on polymorphonuclear leucocyte function in vitro. studied the effects of 6-mercaptopurine on the susceptibility of guinea pigs to experimental allergic encephalomyelitis. 2 reported the harmful effects of the azathioprine metabolite 6-mercaptopurine on vascular cells: induction of mineralization.

Benefits and Risks

Benefit Summary

Mercaptopurine can be an effective treatment for a variety of diseases, including inflammatory bowel disease, cancer, and to suppress the immune system after transplantation. Mercaptopurine can help reduce the symptoms of these diseases and improve quality of life for patients.

Risk Summary

Mercaptopurine can cause a number of side effects, including bone marrow suppression, increased risk of infection, liver dysfunction, nausea, vomiting, and diarrhea. It is also important to note that mercaptopurine can cause birth defects when used during pregnancy. It is essential to understand these risks and discuss them with your doctor before taking mercaptopurine.

Comparison of Studies

Commonalities of Studies

All of these studies investigated the effects of mercaptopurine and its side effects. However, there were differences in the types of diseases studied and the doses of mercaptopurine used.

Differences of Studies

The studies varied in their research methods, dosages used, and diseases they were testing for. For example, focused on the side effects of mercaptopurine, while focused on its effects on cancer.

Consistency and Contradictions in Findings

Many of the studies suggest that mercaptopurine is an effective treatment for inflammatory bowel disease and cancer. However, there are some inconsistencies in the findings regarding the side effects of mercaptopurine. Some studies suggest that it can cause side effects such as bone marrow suppression and increased risk of infection, while others did not find these effects. These inconsistencies could be due to differences in the types of diseases studied, the doses of mercaptopurine used, and the research methods.

Practical Applications and Considerations

While mercaptopurine can be an effective treatment for a number of diseases, it can also cause serious side effects. It is important to understand these risks and discuss them with your doctor before taking mercaptopurine. Additionally, it is important to note that mercaptopurine can cause birth defects when used during pregnancy and should be avoided during that time.

Limitations of Current Research

These studies suggest that further research is needed to better understand the effects and side effects of mercaptopurine. This includes research on specific genetic influences of the drug. More research is especially needed to clarify the inconsistent findings regarding the side effects of mercaptopurine.

Future Research Directions

Future research should investigate the following: * Elucidate the mechanisms by which mercaptopurine causes side effects. * Develop ways to reduce the side effects of mercaptopurine. * Investigate the long-term effects of mercaptopurine use. * Develop methods for determining the optimal dose of mercaptopurine for individual patients.

Conclusion

Mercaptopurine is an effective treatment for a variety of diseases. However, it can also cause serious side effects. It is essential to understand the risks and benefits of mercaptopurine and to discuss them with your doctor before taking this medication. If you are considering taking mercaptopurine, it is important to weigh the potential benefits against the risks.

Literature analysis of 14 papers
Positive Content
9
Neutral Content
1
Negative Content
4
Article Type
2
0
0
0
14
1.

Thiopurine maintenance therapy for ulcerative colitis: the clinical significance of monitoring 6-thioguanine nucleotide.

Author: HanaiHiroyuki, IidaTakayuki, TakeuchiKen, AraiOsamu, WatanabeFumitoshi, AbeJinrou, MaruyamaYasuhiko, OohataAkihiko, IkeyaKentarou, KageokaMasanobu, MiwaIchita, YoshirouSatou, HosodaYoshisuke, KubotaTakahiro

UC treatment
Myelosuppression

Pharmacogenetic guidance of 6-mercaptopurine dose is necessary due to the role of thiopurine methyltransferase polymorphisms in determining therapeutic efficacy and toxicity.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

2.

Harmful effects of the azathioprine metabolite 6-mercaptopurine in vascular cells: induction of mineralization.

Author: PrüferJasmin, SchuchardtMirjam, TölleMarkus, PrüferNicole, HöhneMatthias, ZidekWalter, van der GietMarkus

Arteriosclerosis
Vascular calcification

This study investigated the effects of 6-mercaptopurine (6-MP), an immunosuppressive drug, on vascular calcification. The study found that 6-MP could promote vascular calcification in laboratory tests. This finding suggests that 6-MP may have a harmful effect on blood vessels.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

Differential effects of targeted disruption of thiopurine methyltransferase on mercaptopurine and thioguanine pharmacodynamics.

Author: HartfordChristine, VasquezErick, SchwabMatthias, EdickMathew J, RehgJerold E, GrosveldGerard, PuiChing-Hon, EvansWilliam E, RellingMary V

Leukemic drug therapy
Toxicity

This study investigated the effects of the thiopurine methyltransferase (TPMT) polymorphism on the pharmacokinetics and pharmacodynamics of mercaptopurine and thioguanine in a murine knockout model. The study found that the TPMT polymorphism significantly affects the metabolism of both drugs, with mercaptopurine being more sensitive than thioguanine. The results suggest that the TPMT polymorphism needs to be considered in optimizing drug therapy for individuals receiving thiopurine-based medications.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

5.

Comparison of the effects of azathioprine and its novel non-mercaptopurine analog on antibody response in rabbits.

Author: Al-SafiSaafan, TashtoushBassam, HassanMohamad

Immunosuppression
No bone marrow toxicity

The novel compound 3-[(1-methyl-4-nitro-1H-imidazol-5-yl)thio]-4-methyl-1,2,4-triazole (MNITMT) was found to be a better immunosuppressive agent than azathioprine (AZA). MNITMT inhibited antibody response in rabbits significantly faster than AZA, with no observed bone marrow toxicity.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

6.

Effects on transmethylation by high-dose 6-mercaptopurine and methotrexate infusions during consolidation treatment of acute lymphoblastic leukemia.

Author: Keuzenkamp-JansenC W, De AbreuR A, BlomH J, BökkerinkJ P, TrijbelsJ M

Increased methyl group demand

This study investigated the influence of high-dose 6-mercaptopurine (6MP) on the methylation capacity in children with acute lymphoblastic leukemia.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

De novo purine synthesis inhibition and antileukemic effects of mercaptopurine alone or in combination with methotrexate in vivo.

Author: DervieuxThierry, BrennerTimothy L, HonYuen Y, ZhouYinmei, HancockMichael L, SandlundJohn T, RiveraGaston K, RibeiroRaul C, BoyettJames M, PuiChing-Hon, RellingMary V, EvansWilliam E

Antileukemic effect

Methotrexate (MTX) and mercaptopurine (MP) are effective antileukemic agents that work by inhibiting de novo purine synthesis (DNPS). This study investigated the pharmacodynamic differences between these agents in children with acute lymphoblastic leukemia (ALL). The study found that MTX plus MP produced greater antileukemic effects and DNPS inhibition than MP alone, with full inhibition more frequent after HDMTX.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

12.

Comparison of the effects of mizoribine with those of azathioprine, 6-mercaptopurine, and mycophenolic acid on T lymphocyte proliferation and purine ribonucleotide metabolism.

Author: DaytonJ S, TurkaL A, ThompsonC B, MitchellB S

Selective T cell inhibition
Not applicable

Mizoribine inhibits T cell proliferation by depleting guanine ribonucleotides, while 6MP appears to be more dependent on adenine ribonucleotide depletion. Azathioprine inhibits proliferation by a different mechanism.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

14.

Mercaptopurine in childhood leukaemia: the effects of dose escalation on thioguanine nucleotide metabolites.

Author: LennardL, WelchJ, LilleymanJ S

Higher peak TGN concentrations

Dose escalation of mercaptopurine in children tolerant of 100% dosage resulted in higher peak thioguanine nucleotide concentrations.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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