RBC 6-TGN and hematological parameters in patients with Crohn's disease treated by azathioprine.
OBJECTIVE
The immunosuppressive properties of azathioprine (AZA) are mediated by intracellular metabolism of 6-MP into its active metabolites 6-thiguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP). The aims of this study were to correlate red blood cell (RBC) 6-TGN and hematological parameters and their change in adult patients with Crohn's disease (CD) treated by AZA and to determine independent factors enabling determination of RBC 6-TGN.


METHODS
RBC 6-TGN concentration was determined with high performance liquid chromography (HLPC) performed on 74 hepa-rinized blood samples from 32 patients. Changes of hematological parameters were measured for each RBC 6-TGN concentration. RBC 6-TGN concentration above 235 pmol/8x108 RBC was proposed as the therapeutic level in patients treated by AZA. Correlations between the various parameters were assessed as appropriate. Logistic regression analysis was used to determinate independent variables. P<0.05 was considered significant.


RESULTS
There was a positive correlation between RBC 6-TGN and decreased red cell count (DeltaRBC) (r=0.314; P=0.006), platelet count (DeltaPlatelets) (r=0.314; P=0.007), White cell count (DeltaWC) (r=0.241; P=0.04) and neutrophil count (DeltaPMN) (r=0.292; P=0.02). RBC 6-TGN in the therapeutic zone was positively correlated with mean corpuscular volume (MCV) (r=0.527; P=0.01), mean corpuscular hemoglobin concentration (MCHC) (r=0.437; P=0.04), increase in MCV (DeltaMCV) (r=0.512; P=0.012), decrease in White cell count (DeltaWC) (r=0451; P=003) and in neutrophil count (DeltaPMN) (r=0.463; P=0.03). Multivariate analysis showed that low activity of CD (P<0.02), young age at onset of treatment by AZA (P<0.03) and a low red cell distribution width (RDW) (P=0.003) were independent factors for RBC 6-TGN situated in therapeutic zone. RBC 6-TGN could be determined by logistic regression from AZA dose (mg/kg/d) and MCV increase.


CONCLUSIONS
This study confirms that hematological parameters or their change can be used to determine whether RBC 6-TGN concentration has reached the therapeutic level. Logistic regression analysis showed that decreased RDW and increased MCV were independent factors for RBC 6-TGN level.
D'Halluin
Pierre-Nicolas
PN
Service des Maladies de l'Appareil Digestif (SMAD), Hôpital Pontchaillou Rennes, 35033 Rennes Cedex.
Tribut
Olivier
O
Branger
Bernard
B
Lebreton
Christine
C
Bretagne
Jean-François
JF
Bentue-Ferrer
Danièle
D
Heresbach
Denis
D
D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use*; D001772:Blood Cell Count; D003424:Crohn Disease / Q000097:blood* / Q000188:drug therapy*; D004909:Erythrocyte Indices; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006150:Guanine Nucleotides / Q000097:blood*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D013873:Thionucleotides / Q000097:blood*
D006150:Guanine Nucleotides; D007166:Immunosuppressive Agents; D013873:Thionucleotides; C003964:6-thioguanylic acid; D001379:Azathioprine