Steady-state of azathioprine during initiation treatment of pediatric inflammatory bowel disease.
OBJECTIVE
Azathioprine (AZA) has a slow onset of action in treatment of pediatric inflammatory bowel disease (IBD). It is anticipated, that this delay correlates to the kinetics of 6-thioguanine nucleotides (6-TGN) accumulation. The aim of this study was to evaluate the time to steady state of 6-TGN concentration in red blood cells.


METHODS
The inclusion criteria were: a) age 0-19 years b) IBD diagnosis c) AZA treatment initiation. High performance liquid chromatography was used for the 6-TGN analysis. Concentrations of metabolites were studied in weeks 0, 1, 2, 5, and 8 after beginning of treatment.


RESULTS
The inclusion criteria were matched to 18 patients with IBD. The median time to steady state of 6-TGN was 55.3 days. The mean 6-TGN concentration at the steady state achieved 326 (SD 154) pmol/8.108 erythrocytes. High erythrocyte TPMT activity corresponds to the low steady state 6-TGN concentration and vice versa. This correlation reached statistical significance (p<0.01) for the dose expressed in mg per square meter of body surface area.


CONCLUSIONS
The time to steady state of 6-TGN erythrocyte concentration is significantly shorter than would expected according to clinical observation describe earlier.
Dept. of Pediatrics, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Králové, Czech Republic. pozler@lfhk.cuni.cz
O
O
Pozler
J
J
Chládek
J
J
Malý
M
M
Hroch
P
P
Dědek
M
M
Beránek
P
P
Krásničanová
D000293:Adolescent; D001379:Azathioprine / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006150:Guanine Nucleotides / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D015122:Mercaptopurine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D011446:Prospective Studies; D012720:Severity of Illness Index; D013873:Thionucleotides / Q000097:blood / Q000493:pharmacokinetics*; D016896:Treatment Outcome
D006150:Guanine Nucleotides; D007166:Immunosuppressive Agents; D013873:Thionucleotides; C003964:6-thioguanylic acid; C010240:6-methylthiopurine; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine