High variation of tioguanine absorption in patients with chronic active Crohn's disease.
BACKGROUND
Tioguanine (thioguanine) has been suggested as a therapeutic alternative for patients with Crohn's disease resistant or intolerant to azathioprine or mercaptopurine. However, pharmacokinetic data on tioguanine in inflammatory bowel disease are missing.


OBJECTIVE
To determine the disposition of three different 40 mg tablet preparations of tioguanine in patients with Crohn's disease.


METHODS
Six patients with chronic active Crohn's disease were included in a randomized, cross-over, single-dose study. Pharmacokinetic analysis was based on plasma concentrations of tioguanine during 6 h after dosing. Tioguanine was measured by a validated high-pressure liquid chromatographic method.


RESULTS
The areas under the curve (AUC) varied 4-7-fold between patients. In two patients, tioguanine was not detected in plasma following the intake of one of the three tablets; another patient did not absorb tioguanine in two of the three different preparations. No significant differences were found in the AUC and Cmax values between the three tablets. In all patients, there was a second peak in plasma concentration following a meal 3 h after drug administration.


CONCLUSIONS
The absorption of tioguanine is highly variable in patients with Crohn's disease, which may be responsible for treatment failure. Therapy with tioguanine may be improved by monitoring tioguanine nucleotides as a surrogate parameter of efficacy.
Deibert
P
P
Department for Preventive and Rehabilitative Sports Medicine, University Hospital, Freiburg, Germany. deibert@msm1.ukl.uni-freiburg.de
Dilger
K
K
Fischer
C
C
Hofmann
U
U
Nauck
S
S
Stoelben
S
S
Kreisel
W
W
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy* / Q000378:metabolism; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D013866:Thioguanine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D013866:Thioguanine