Relationship between red cell mean corpuscular volume and 6-thioguanine nucleotides in patients treated with azathioprine

Azathioprine (AZA) is characterized by high interindividual differences in bioavailability and metabolization. The aim of the present study was to ana lyze, in patients treated with AZA for various immune system disorders, whe ther the variation in red blood cell mean corpuscular volume (Delta MCV) co uld be used as an indirect estimation of the level of the active immune mod ifier metabolite 6-thioguanine nucleotides (6-TGN), In 43 consecutive patie nts treated with a stable dose of AZA for at least 6 months who were not in itially anemic, the erythrocyte 6-TGN levels with routine hematologic param eters were determined two to four times at 1-month intervals. In most patie nts MCV significantly increased after 3 months of therapy and stabilized af ter 6 months. The correlation between the daily dose of AZA and the 6-TGN l evel was mild (r = 0.51; P < .001). A weak correlation was also found betwe en the dose of AZA and the Delta MCV after at least 6 months of therapy (r = 0.36; P < .05), The correlation between Delta MCV and 6-TGN level, howeve r, was much better (r = 0.74; P < .001), The lack of a significant increase in MCV after 3 to 4 months of AZA therapy reflects low 6-TGN levels, somet imes a result of undertreatment. A determination of the 6-TGN level during the first months after AZA therapy is begun will allow more accurate adapta tion of the effective dose. We observed that Delta MCV could be used as an indicator of 6-TGN levels after 6 months of AZA treatment. An increase in M CV of at least 6 fL is expected to reflect a 6-TGN level of about 175 pmol/ 8 x 10(8) red blood cells (probably being within a therapeutic value).