PMID- 23424097
OWN - NLM
STAT- MEDLINE
DCOM- 20140414
LR  - 20171116
IS  - 1468-3288 (Electronic)
IS  - 0017-5749 (Linking)
VI  - 63
IP  - 3
DP  - 2014 Mar
TI  - Intrauterine exposure and pharmacology of conventional thiopurine therapy in 
      pregnant patients with inflammatory bowel disease.
PG  - 451-7
LID - 10.1136/gutjnl-2012-303615 [doi]
AB  - OBJECTIVE: Several studies have demonstrated a favourable safety profile for 
      thiopurine use for inflammatory bowel disease (IBD) during pregnancy. We 
      performed a study in pregnant patients with IBD who were using thiopurines, in 
      order to determine the influence of pregnancy on thiopurine metabolism and to 
      assess intrauterine exposure of the fetus to thiopurines. DESIGN: Female patients 
      with IBD receiving steady-state thiopurines and planning a pregnancy were 
      prospectively enrolled. 6-Thioguanine nucleotide (6-TGN) and 
      6-methylmercaptopurine (6-MMP) concentrations were determined, combined with 
      routine laboratory tests, before, during and after pregnancy. Thiopurine 
      metabolites were measured in umbilical cord blood immediately after delivery. 
      RESULTS: Thirty patients who were using azathioprine (28 patients, median dose 
      1.93 mg/kg) or mercaptopurine (two patients, doses 1.32 and 0.94 mg/kg) were 
      included. During pregnancy, median 6-TGN decreased over time (p=0.001). while 
      6-MMP increased, without causing myelotoxicity or hepatotoxicity. After delivery, 
      both 6-TGN and 6-MMP levels returned to preconception baseline levels. Fetal 
      6-TGN concentrations correlated positively with maternal 6-TGN levels (p<0.0001). 
      No 6-MMP was detected in the newborns, except one born with pancytopenia and high 
      alkaline phosphatase activity; the mother of this infant had severe 
      pre-eclampsia. All infants had normal Apgar scores, but 60% had anaemia at birth. 
      No major congenital abnormalities were observed. CONCLUSIONS: Pregnancy has a 
      major effect on maternal thiopurine metabolism. In utero the unborn child is 
      exposed to 6-TGN, but not to 6-MMP. Sixty per cent of the infants were born with 
      anaemia, which raises the question whether infants should be tested for possible 
      anaemia immediately after birth.
FAU - Jharap, Bindia
AU  - Jharap B
AD  - Department of Gastroenterology and Hepatology, VU University Medical Center, , 
      Amsterdam, The Netherlands.
FAU - de Boer, Nanne K H
AU  - de Boer NK
FAU - Stokkers, Pieter
AU  - Stokkers P
FAU - Hommes, Daniel W
AU  - Hommes DW
FAU - Oldenburg, Bas
AU  - Oldenburg B
FAU - Dijkstra, Gerard
AU  - Dijkstra G
FAU - van der Woude, C Janneke
AU  - van der Woude CJ
FAU - de Jong, Dirk J
AU  - de Jong DJ
FAU - Mulder, Chris J J
AU  - Mulder CJ
FAU - van Elburg, Ruurd M
AU  - van Elburg RM
FAU - van Bodegraven, Adriaan A
AU  - van Bodegraven AA
CN  - Dutch Initiative on Crohn and Colitis
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130219
PL  - England
TA  - Gut
JT  - Gut
JID - 2985108R
RN  - 0 (Biomarkers)
RN  - 0 (Guanine Nucleotides)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Thionucleotides)
RN  - 15867-02-4 (6-thioguanylic acid)
RN  - 6V404DV25O (6-methylthiopurine)
RN  - E7WED276I5 (Mercaptopurine)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - Abnormalities, Drug-Induced/etiology
MH  - Adolescent
MH  - Adult
MH  - Anemia, Neonatal/chemically induced
MH  - Azathioprine/adverse effects/pharmacokinetics/therapeutic use
MH  - Biomarkers/blood
MH  - Female
MH  - Fetal Blood/*chemistry
MH  - Follow-Up Studies
MH  - Guanine Nucleotides/*blood
MH  - Humans
MH  - Immunosuppressive Agents/adverse effects/*pharmacokinetics/therapeutic use
MH  - Infant, Newborn
MH  - Inflammatory Bowel Diseases/blood/*drug therapy
MH  - Mercaptopurine/adverse effects/*analogs & 
      derivatives/blood/*pharmacokinetics/therapeutic use
MH  - Middle Aged
MH  - Pregnancy
MH  - Pregnancy Complications/blood/*drug therapy
MH  - Pregnancy Outcome
MH  - Prospective Studies
MH  - Thionucleotides/*blood
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - Drug Metabolism
OT  - Ibd Clinical
OT  - Inflammatory Bowel Disease
OT  - Pharmacokinetics
EDAT- 2013/02/21 06:00
MHDA- 2014/04/15 06:00
CRDT- 2013/02/21 06:00
PHST- 2013/02/21 06:00 [entrez]
PHST- 2013/02/21 06:00 [pubmed]
PHST- 2014/04/15 06:00 [medline]
AID - gutjnl-2012-303615 [pii]
AID - 10.1136/gutjnl-2012-303615 [doi]
PST - ppublish
SO  - Gut. 2014 Mar;63(3):451-7. doi: 10.1136/gutjnl-2012-303615. Epub 2013 Feb 19.