PMID- 24523395
OWN - NLM
STAT- MEDLINE
DCOM- 20141113
LR  - 20171116
IS  - 1542-6270 (Electronic)
IS  - 1060-0280 (Linking)
VI  - 48
IP  - 5
DP  - 2014 May
TI  - Febuxostat as a novel option to optimize thiopurines' metabolism in patients with 
      inadequate metabolite levels.
PG  - 648-51
LID - 10.1177/1060028014521389 [doi]
AB  - OBJECTIVE: To report the use of febuxostat in order to potentiate thiopurines' 
      metabolism in a patient on azathioprine (AZA) therapy with low metabolite 
      6-thioguanine nucleotides (6-TGN) levels and elevated metabolite 
      6-methylmercaptopurine (6-MMP) levels. CASE SUMMARY: A 44-year-old woman with a 
      history of anti-signal recognition particle necrotizing myopathy was treated with 
      AZA-allopurinol combination therapy. When she developed an atypical drug-induced 
      hypersensitivity syndrome, allopurinol was replaced by the new xanthine oxidase 
      (XO) inhibitor febuxostat, at a daily dose of 40 mg. Febuxostat-AZA combination 
      was successful with 6-TGN reaching therapeutic levels while 6-MMP levels remained 
      low. After 5 months, she developed similar manifestations that she had presented 
      on AZA-allopurinol combination. Febuxostat and AZA were then stopped. DISCUSSION: 
      AZA and 6-MP are both inactive pro-drugs that undergo a complex metabolic 
      transformation leading to active 6-TGN and potentially hepatotoxic 6-MMP. Some 
      patients with unfavorable thiopurine metabolism might benefit from addition of XO 
      inhibitor allopurinol in order to potentiate 6-TGN and reduce 6-MMP levels. It is 
      likely that febuxostat, via its XO inhibition, would exhibit the same effect on 
      thiopurines' metabolism. CONCLUSION: It has been shown that low dose of 
      febuxostat was able to prevent hypermethylation and to potentiate 6-TGN levels in 
      an AZA-treated patient. Thus, febuxostat could be useful in optimizing 
      thiopurines' metabolism, but more data are needed before this practice can be 
      recommended. The mechanisms by which febuxostat optimizes thiopurines' metabolism 
      remain to be confirmed. Also, the optimal dose of febuxostat for this use remains 
      to be determined.
FAU - Dore, Maxime
AU  - Dore M
AD  - Hopital du Sacre-Coeur de Montreal, Montreal, Quebec, Canada.
FAU - Frenette, Anne Julie
AU  - Frenette AJ
FAU - Mansour, Anne-Marie
AU  - Mansour AM
FAU - Troyanov, Yves
AU  - Troyanov Y
FAU - Begin, Josiane
AU  - Begin J
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20140212
PL  - United States
TA  - Ann Pharmacother
JT  - The Annals of pharmacotherapy
JID - 9203131
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Guanine Nucleotides)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Thiazoles)
RN  - 0 (Thionucleotides)
RN  - 101V0R1N2E (Febuxostat)
RN  - 15867-02-4 (6-thioguanylic acid)
RN  - 6V404DV25O (6-methylthiopurine)
RN  - E7WED276I5 (Mercaptopurine)
RN  - EC 1.17.3.2 (Xanthine Oxidase)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - Adult
MH  - Azathioprine/*administration & dosage
MH  - Drug Interactions
MH  - Enzyme Inhibitors/*administration & dosage
MH  - Febuxostat
MH  - Female
MH  - Guanine Nucleotides/*blood
MH  - Humans
MH  - Immunosuppressive Agents/*administration & dosage
MH  - Mercaptopurine/*analogs & derivatives/blood
MH  - Muscular Diseases/*drug therapy
MH  - Thiazoles/*administration & dosage
MH  - Thionucleotides/*blood
MH  - Xanthine Oxidase/antagonists & inhibitors
OTO - NOTNLM
OT  - 6-mercaptopurine
OT  - allopurinol
OT  - azathioprine
OT  - drug-induced hypersensitivity syndrome
OT  - febuxostat
OT  - hypermethylation
OT  - thiopurine S-methyltransferase
OT  - thiopurines
OT  - xanthine oxidase
EDAT- 2014/02/14 06:00
MHDA- 2014/11/14 06:00
CRDT- 2014/02/14 06:00
PHST- 2014/02/14 06:00 [entrez]
PHST- 2014/02/14 06:00 [pubmed]
PHST- 2014/11/14 06:00 [medline]
AID - 1060028014521389 [pii]
AID - 10.1177/1060028014521389 [doi]
PST - ppublish
SO  - Ann Pharmacother. 2014 May;48(5):648-51. doi: 10.1177/1060028014521389. Epub 2014 
      Feb 12.