Dose-dependent influence of 5-aminosalicylates on thiopurine metabolism.
BACKGROUND
Studies indicated that 5-aminosalicylates (5-ASA) may influence the metabolism of thiopurines; however, conclusions were restricted as a result of number of patients or study design.


OBJECTIVE
To determine the influence of 5-ASA on thiopurine metabolism, we performed a prospective multicenter pharmacokinetic interaction study of two different 5-ASA dosages (2 g daily followed by 4 g daily) in 26 inflammatory bowel disease (IBD) patients during steady-state AZA or 6-MP therapy.


RESULTS
The 4-wk coadministration of 2 g 5-ASA daily, followed by a 4-wk period of 4 g 5-ASA daily, led to a statistical significant increase of 40% (absolute 84 pmol/8x10(8) RBC) and 70% (absolute 154 pmol/8x10(8) RBC) in 6-thioguaninenucleotide levels (6-TGN), respectively. A rise in 6-TGN levels was observed in 100% of patients after a 4-wk period of 4 g 5-ASA daily. The 6-methylmercaptopurine-ribonucleotide levels did not change. Signs of myelotoxicity were observed in 7.7% of patients (N=2).


CONCLUSIONS
The level of the pharmacologically active 6-TGN significantly increases in a dose-dependent manner during 5-ASA coadministration. IBD patients who are unresponsive or refractory to standard thiopurine therapy may benefit from the coadministration of 5-ASA, leading to an increase in 6-TGN levels.
de Boer
Nanne K H
NK
Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
Wong
Dennis R
DR
Jharap
Bindia
B
de Graaf
Peer
P
Hooymans
Piet M
PM
Mulder
Chris J J
CJ
Rijmen
Frank
F
Engels
Leopold G J B
LG
van Bodegraven
Adriaan A
AA
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008780:Methyltransferases / Q000378:metabolism*; D011446:Prospective Studies; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine; D008780:Methyltransferases; C022745:thiopurine methyltransferase