Determination of 6-thioguanine and 6-methylmercaptopurine metabolites in renal transplantation recipients and patients with glomerulonephritis treated with azathioprine

The metabolism of azathioprine (AZA) was studied by monitoring the concentr ations of red blood cell (RBC) B-thioguanine nucleotides (6-TGN) and of 6-m ethylmercaptopurine metabolites (6-mMP) in 27 renal transplantation recipie nts and in 10 patient subjects with glomerulonephritis (GN). Concentrations of 6-TGNs and 6-mMP metabolites were measured using high-performance liqui d chromatography (HPLC). Six patients from the group of renal transplantati on recipients were also administered allopurinol. Median values of RBC 6-TG N and of 6-mMP metabolites concentrations in 21 renal transplantation recip ients (without allopurinol) were 122 pmol / 8x10(8) RBCs (range, <60-298) a nd 280 pmol / 8x10(8) RBC (range, <150-1330), respectively; there was no co rrelation between concentrations of 6-TGN and of 6-mMP metabolites. The gro up of 21 renal transplantation recipients received different AZA doses (100 or 50 mg/d) related to clinical symptoms of AZA intolerance. The median va lues of 6-TGN concentrations in these subgroups were 131 and 122 pmol / 8x1 08 RBCs and were not significantly different. Median values of 6-TGN concen trations in patients given allopurinol were significantly higher, despite A ZA dose reduction, compared with the group without allopurinol and were equ al to 363 and 122 pmol / 8x10(8) RBC, p < 0.003, respectively. No significa nt differences were found between the concentrations of 6-mMP metabolites i n either group. In the group of renal trans plantation recipients, a signif icant correlation between white blood cell (WBC) count and 6-TGN concentrat ion was established (r(s) = -0.59, p < 0.005). In the group of GN patients, the median values of 6-TGN and of 6-mMP metabolites concentrations were 10 8 pmol / 8x10(8) RBCs (range, 0-297) and 420 pmol / 8x10(8) RBC (range, 0-1 440), respectively. There were no significant correlations between either t he WBC count and 6-TGN concentrations or between 6-TGN concentrations and 6 -mMP metabolites. We expect the results of our study to provide indications for better individualization of AZA therapy.