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 aim...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 heparinized blood samples from 32 patients. Changes of hematological parameters were measured for each RBC 6-TGN concentration. RBC 6-TGN concentration above 235 pmol/8×108 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 (ΔRBC) (r = 0.314; P = 0.006), platelet count (ΔPlatelets) (r = 0.314; P = 0.007), White cell count (ΔWC) (r = 0.241; P = 0.04) and neutrophil count (ΔPMN) (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 (ΔMCV) (r = 0.512; P = 0.012), decrease in White cell count (ΔWC) (r = 0451; P = 003) and in neutrophil count (ΔPMN) (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. Conclusion-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 MCVwere independent factors forRBC6-TGN level.展开更多
文摘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 heparinized blood samples from 32 patients. Changes of hematological parameters were measured for each RBC 6-TGN concentration. RBC 6-TGN concentration above 235 pmol/8×108 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 (ΔRBC) (r = 0.314; P = 0.006), platelet count (ΔPlatelets) (r = 0.314; P = 0.007), White cell count (ΔWC) (r = 0.241; P = 0.04) and neutrophil count (ΔPMN) (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 (ΔMCV) (r = 0.512; P = 0.012), decrease in White cell count (ΔWC) (r = 0451; P = 003) and in neutrophil count (ΔPMN) (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. Conclusion-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 MCVwere independent factors forRBC6-TGN level.
