PMID- 20590602
OWN - NLM
STAT- MEDLINE
DCOM- 20101007
LR  - 20211020
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 160
IP  - 5
DP  - 2010 Jul
TI  - Influence of 5-aminosalicylic acid on 6-thioguanosine phosphate metabolite 
      levels: a prospective study in patients under steady thiopurine therapy.
PG  - 1083-91
LID - 10.1111/j.1476-5381.2010.00731.x [doi]
AB  - BACKGROUND AND PURPOSE: 5-aminosalicylate (5-ASA) raises levels of 6-thioguanine 
      nucleotides (6-TGN), the active metabolites of thiopurines such as azathioprine 
      (AZA). Changes in levels of each individual TGN - 6-thioguanosine mono-, di- and 
      triphosphate (6-TGMP, 6-TGDP, 6-TGTP) - and of 6-methylmercaptopurine 
      ribonucleotides (6-MMPR) after 5-ASA are not known. EXPERIMENTAL APPROACH: 
      Effects of increasing 5-ASA doses on AZA metabolites were investigated 
      prospectively in 22 patients with inflammatory bowel disease in 4-week study 
      periods. Patients started with 2 g 5-ASA daily, and then were increased to 4 g 
      daily and followed by a washout period. Thiopurine doses remained unchanged 
      throughout the entire study. Levels of 6-TGMP, 6-TGDP, 6-TGTP and 6-MMPR as well 
      as of 5-ASA and N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA) were determined each 
      study period. KEY RESULTS: Median baseline levels in 17 patients of 6-TGDP, 
      6-TGTP and 6-MMPR were 52, 319 and 1676 pmol per 8 x 10(8) red blood cells 
      respectively. After co-administration of 2 g 5-ASA daily, median 6-TGDP and 
      6-TGTP levels increased but median 6-MMPR levels were unchanged. Increasing 5-ASA 
      to 4 g daily did not affect median 6-TGDP and 6-TGTP levels, but median 6-MMPR 
      levels decreased. After discontinuation of 5-ASA, both 6-TGDP and 6-TGTP levels 
      decreased and median 6-MMPR levels increased. The 6-TGTP/(6-TGDP+6-TGTP)-ratio 
      did not change during the study, but 6-MMPR/6-TGN ratios decreased. CONCLUSIONS 
      AND IMPLICATIONS: Individual 6-TGN metabolites increased after addition of 5-ASA, 
      but 6-MMPR-levels and the 6-MMPR/6-TGN ratios decreased. Further studies are 
      needed to decide whether this pharmacokinetic interaction would result in 
      improvement of efficacy and/or increased risk of toxicity of AZA.
FAU - de Graaf, P
AU  - de Graaf P
AD  - Clinical Pharmacology & Pharmacy, VU University Medical Center, Amsterdam, the 
      Netherlands. Peer.deGraaf@vumc.nl
FAU - de Boer, N K H
AU  - de Boer NK
FAU - Wong, D R
AU  - Wong DR
FAU - Karner, S
AU  - Karner S
FAU - Jharap, B
AU  - Jharap B
FAU - Hooymans, P M
AU  - Hooymans PM
FAU - Veldkamp, A I
AU  - Veldkamp AI
FAU - Mulder, C J J
AU  - Mulder CJ
FAU - van Bodegraven, A A
AU  - van Bodegraven AA
FAU - Schwab, M
AU  - Schwab M
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Immunosuppressive Agents)
RN  - 4Q81I59GXC (Mesalamine)
RN  - E7WED276I5 (Mercaptopurine)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - Adult
MH  - Anti-Inflammatory Agents, Non-Steroidal/administration & 
      dosage/pharmacokinetics/*pharmacology
MH  - Azathioprine/*pharmacokinetics/therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Drug Therapy, Combination
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/*pharmacokinetics
MH  - Inflammatory Bowel Diseases/drug therapy/*metabolism
MH  - Male
MH  - Mercaptopurine/pharmacokinetics/therapeutic use
MH  - Mesalamine/administration & dosage/pharmacokinetics/*pharmacology
MH  - Middle Aged
MH  - Prospective Studies
PMC - PMC2936018
EDAT- 2010/07/02 06:00
MHDA- 2010/10/12 06:00
PMCR- 2011/07/01
CRDT- 2010/07/02 06:00
PHST- 2010/07/02 06:00 [entrez]
PHST- 2010/07/02 06:00 [pubmed]
PHST- 2010/10/12 06:00 [medline]
PHST- 2011/07/01 00:00 [pmc-release]
AID - BPH731 [pii]
AID - 10.1111/j.1476-5381.2010.00731.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 2010 Jul;160(5):1083-91. doi: 10.1111/j.1476-5381.2010.00731.x.