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Mutation Research Sep 1989Azathioprine, an immunosuppressive drug, has been used for 25 years. Azathioprine is rapidly converted into a number of metabolites after absorption. Maximum blood... (Review)
Review
Azathioprine, an immunosuppressive drug, has been used for 25 years. Azathioprine is rapidly converted into a number of metabolites after absorption. Maximum blood levels in experimental animals (mice) were 11.3 micrograms/ml after a dosage of 33.3 mg/kg. Generally, levels of less than 1 microgram/ml are found. As azathioprine is ineffective in hypoxanthine guanine phosphoribosyltransferase (HPRT)-deficient patients, it will be clear that for immunosuppressive activity azathioprine must be metabolised. Regarding mutagenic activity, its mutagenicity for bacteria seems irrelevant for man because the nitroimidazole moiety can be reduced by bacteria but not or hardly at all by mammalian tissues. So 6-mercaptopurine (a metabolite of azathioprine) and its metabolites should be regarded as the active compounds. In vitro azathioprine can induce chromosome aberrations and other cytogenetic events at high, non-physiological doses. However, in view of the low blood levels it is unlikely that azathioprine can induce chromosome aberrations in kidney transplant patients. It is more probable that azathioprine inhibits the elimination of such aberrant cells through its immunosuppressive activity. It should be pointed out that in microbial mutagenicity systems also, azathioprine concentrations that are not reached in patients are needed to obtain an increased mutation rate.
Topics: Animals; Azathioprine; Carcinogens; Humans; Mutagenicity Tests; Mutagens; Mutation; Teratogens
PubMed: 2671708
DOI: 10.1016/0165-1110(89)90002-x -
The Journal of Rheumatology Dec 2017
Topics: Adult; Azathioprine; Drug Hypersensitivity Syndrome; Female; Humans; Lupus Erythematosus, Systemic
PubMed: 29196546
DOI: 10.3899/jrheum.170066 -
Der Internist Aug 1993
Review
Topics: Autoimmune Diseases; Azathioprine; Drug Interactions; Graft Rejection; Humans
PubMed: 8375993
DOI: No ID Found -
Journal of Hepatology Jul 2024
Comparative Study
Topics: Humans; Mycophenolic Acid; Hepatitis, Autoimmune; Azathioprine; Immunosuppressive Agents
PubMed: 38458322
DOI: 10.1016/j.jhep.2024.02.022 -
Journal of Neurology, Neurosurgery, and... Feb 2009Azathioprine (AZA) is an immunosuppressive drug widely prescribed for the treatment of multiple sclerosis (MS) until the first half of the 1990s. It could be an...
BACKGROUND
Azathioprine (AZA) is an immunosuppressive drug widely prescribed for the treatment of multiple sclerosis (MS) until the first half of the 1990s. It could be an alternative to interferon beta because it is less expensive. Concerns about its safety, mainly a possible increased risk of malignancy, have been raised. This systematic review aimed to determine the trade off between the benefits and risks of azathioprine in MS.
OBJECTIVES
To compare azathioprine with placebo. To assess the effect of azathioprine on major clinical outcomes (ie, disability progression and relapses) in patients with MS, and to evaluate the drug's safety.
METHODS
The Cochrane MS Group search strategy was adopted to identify relevant articles. All randomised controlled trials comparing azathioprine treatment of a least 1 year duration with placebo for patients with MS were eligible for the review. Cohorts, case controls, case series and case reports were also considered to assess adverse effects. Regulatory agencies were additional sources of information for adverse effects. More details are available in the full review.
Topics: Azathioprine; Humans; Immunosuppressive Agents; Multiple Sclerosis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 19151017
DOI: 10.1136/jnnp.2008.144972 -
BMJ Open Respiratory Research Feb 2024Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the efficacy of MMF or AZA on pulmonary function in ILD.
DESIGN
Population included any ILD diagnosis, intervention included MMF or AZA treatment, outcome was delta change from baseline in per cent predicted forced vital capacity (%FVC) and gas transfer (diffusion lung capacity of carbon monoxide, %DLco). The primary endpoint compared outcomes relative to placebo comparator, the secondary endpoint assessed outcomes in treated groups only.
ELIGIBILITY CRITERIA
Randomised controlled trials (RCTs) and prospective observational studies were included. No language restrictions were applied. Retrospective studies and studies with high-dose concomitant steroids were excluded.
DATA SYNTHESIS
The systematic search was performed on 9 May. Meta-analyses according to drug and outcome were specified with random effects, I evaluated heterogeneity and Grading of Recommendations, Assessment, Development and Evaluation evaluated certainty of evidence. Primary endpoint analysis was restricted to RCT design, secondary endpoint included subgroup analysis according to prospective observational or RCT design.
RESULTS
A total of 2831 publications were screened, 12 were suitable for quantitative synthesis. Three MMF RCTs were included with no significant effect on the primary endpoints (%FVC 2.94, 95% CI -4.00 to 9.88, I=79.3%; %DLco -2.03, 95% CI -4.38 to 0.32, I=0.0%). An overall 2.03% change from baseline in %FVC (95% CI 0.65 to 3.42, I=0.0%) was observed in MMF, and RCT subgroup summary estimated a 4.42% change from baseline in %DL (95% CI 2.05 to 6.79, I=0.0%). AZA studies were limited. All estimates were considered very low certainty evidence.
CONCLUSIONS
There were limited RCTs of MMF or AZA and their benefit in ILD was of very low certainty. MMF may support preservation of pulmonary function, yet confidence in the effect was weak. To support high certainty evidence, RCTs should be designed to directly assess MMF efficacy in ILD.
PROSPERO REGISTRATION NUMBER
CRD42023423223.
Topics: Humans; Azathioprine; Immunosuppressive Agents; Lung Diseases, Interstitial; Lung; Mycophenolic Acid; Enzyme Inhibitors; Observational Studies as Topic
PubMed: 38413120
DOI: 10.1136/bmjresp-2023-002163 -
British Journal of Rheumatology Aug 1998
Review
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Azathioprine; Cyclophosphamide; Humans
PubMed: 9734673
DOI: 10.1093/rheumatology/37.8.824 -
International Journal of Molecular... Jun 2021The electrochemical behavior and the interaction of the immunosuppressive drug azathioprine (AZA) with deoxyribonucleic acid (DNA) were investigated using voltammetric...
The electrochemical behavior and the interaction of the immunosuppressive drug azathioprine (AZA) with deoxyribonucleic acid (DNA) were investigated using voltammetric techniques, mass spectrometry (MS), and scanning electron microscopy (SEM). The redox mechanism of AZA on glassy carbon (GC) was investigated using cyclic and differential pulse (DP) voltammetry. It was proven that the electroactive center of AZA is the nitro group and its reduction mechanism is a diffusion-controlled process, which occurs in consecutive steps with formation of electroactive products and involves the transfer of electrons and protons. A redox mechanism was proposed and the interaction of AZA with DNA was also investigated. Morphological characterization of the DNA film on the electrode surface before and after interaction with AZA was performed using scanning electron microscopy. An electrochemical DNA biosensor was employed to study the interactions between AZA and DNA with different concentrations, incubation times, and applied potential values. It was shown that the reduction of AZA molecules bound to the DNA layer induces structural changes of the DNA double strands and oxidative damage, which were recognized through the occurrence of the 8-oxo-deoxyguanosine oxidation peak. Mass spectrometry investigation of the DNA film before and after interaction with AZA also demonstrated the formation of AZA adducts with purine bases.
Topics: Algorithms; Azathioprine; Biosensing Techniques; Chemical Phenomena; DNA; Macromolecular Substances; Mass Spectrometry; Models, Theoretical; Oxidation-Reduction
PubMed: 34202734
DOI: 10.3390/ijms22136805 -
Proceedings of the Royal Society of... Aug 1973
Topics: Adult; Aged; Azathioprine; Biopsy; Cholestasis; Female; Humans; Liver; Liver Cirrhosis; Male; Middle Aged; Psoriasis
PubMed: 4733959
DOI: No ID Found -
British Medical Journal Apr 1970
Topics: Adult; Aged; Azathioprine; Female; Humans; Male; Middle Aged; Psoriasis
PubMed: 5443416
DOI: 10.1136/bmj.2.5703.237-b