PMID- 16518285 OWN - NLM STAT- MEDLINE DCOM- 20060420 LR - 20201105 IS - 0399-8320 (Print) IS - 0399-8320 (Linking) VI - 29 IP - 12 DP - 2005 Dec TI - RBC 6-TGN and hematological parameters in patients with Crohn's disease treated by azathioprine. PG - 1264-9 AB - 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. 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 MCV were independent factors for RBC 6-TGN level. FAU - D'Halluin, Pierre-Nicolas AU - D'Halluin PN AD - Service des Maladies de l'Appareil Digestif (SMAD), Hopital Pontchaillou Rennes, 35033 Rennes Cedex. FAU - Tribut, Olivier AU - Tribut O FAU - Branger, Bernard AU - Branger B FAU - Lebreton, Christine AU - Lebreton C FAU - Bretagne, Jean-Francois AU - Bretagne JF FAU - Bentue-Ferrer, Daniele AU - Bentue-Ferrer D FAU - Heresbach, Denis AU - Heresbach D LA - eng PT - Journal Article PL - France TA - Gastroenterol Clin Biol JT - Gastroenterologie clinique et biologique JID - 7704825 RN - 0 (Guanine Nucleotides) RN - 0 (Immunosuppressive Agents) RN - 0 (Thionucleotides) RN - 15867-02-4 (6-thioguanylic acid) RN - MRK240IY2L (Azathioprine) SB - IM MH - Adult MH - Azathioprine/*therapeutic use MH - Blood Cell Count MH - Crohn Disease/*blood/*drug therapy MH - Erythrocyte Indices MH - Erythrocytes/*metabolism MH - Female MH - Guanine Nucleotides/*blood MH - Humans MH - Immunosuppressive Agents/*therapeutic use MH - Male MH - Neutrophils/metabolism MH - Thionucleotides/*blood EDAT- 2006/03/07 09:00 MHDA- 2006/04/21 09:00 CRDT- 2006/03/07 09:00 PHST- 2006/03/07 09:00 [pubmed] PHST- 2006/04/21 09:00 [medline] PHST- 2006/03/07 09:00 [entrez] AID - s0399-8320(05)82219-5 [pii] AID - 10.1016/s0399-8320(05)82219-5 [doi] PST - ppublish SO - Gastroenterol Clin Biol. 2005 Dec;29(12):1264-9. doi: 10.1016/s0399-8320(05)82219-5.