Azathioprine metabolism in kidney transplant recipients.

Abstract

Sheffield S10 2JF 1 Azathioprine metabolite concentrations were studied in 54 kidney transplant recipients. Thirty-seven of these patients were studied over a 6 month period to investigate the intrapatient variation in metabolite concentrations. All patients had stable functioning grafts and normal peripheral white blood cell counts. 2 The metabolites measured were plasma 6-mercaptopurine and red blood cell 6-thioguanine nucleotide. 3 There was no correlation between azathioprine dose and plasma 6-mercaptopurine concentration but there was a significant correlation between dose and red blood cell 6-thioguanine nucleotide concentration (r, = 0.41, P < 0.005). The individual transplant recipient showed little variation in metabolite concentrations over several months. 4 Using this group as a control we studied metabolite concentrations in patients with kidney transplants who developed leucopenia. Our preliminary findings indicate that elevated red cell 6-thioguanine nucleotide concentrations, above the control range, can be associated with bone marrow depression.

Azathioprine or methotrexate in the treatment of patients with steroid‐dependent or steroid‐resistant ulcerative colitis: results of an open‐label study on efficacy and tolerability in inducing and maintaining remission

“…This side‐effect is dose‐related, usually occurs within the first month of drug intake (although, in some cases, the condition has been described after years of treatment 28 ) and often disappears after the reduction of drug dosage. In the present investigation, leucopenia occurred with a higher rate (21%) than that reported in previous papers (2–15%) 28 , 29 after a few days of treatment with azathioprine, did not regress after reduction of the daily dose and interruption of therapy was necessary in all nine patients. Although, in some cases, azathioprine was prescribed at a slightly higher (2.3 mg/kg) daily dosage, patients who developed leucopenia were given the drug at a daily dosage of 2.0 mg/kg.…”

The Use of Therapeutic Drug Monitoring to Optimise Immunosuppressive Therapy

“…In a study of 65 renal tran splant recip ients, high concentrations of 6-thioguanine nucleotides in erythrocytes [>200 pmol/(8 x 10 8 red blood cell s)] corresponded to both a lower mean nadir neutrophil count and average delay in the nadir neutrophil count compared with low 6-thioguanine nucleotide concentrations.U'vl In an earlier study of 54 renal transplant recipients, an inverse correlation between 6-thioguanine nucleotides and absolute neutrophil count was found in female but not in male patients. [274) Finally, concentrations of 6-thioguanine nucleotides were measured in 16 heart tran splant patients. In 15 patients without severe leucopenia, 6-thioguanine nucleotide concentrations were low [ranging from <30 to 431 pmol/(8 x 10 8 red blood cells) with a median count of 63]; however, in 1 patient experiencing severe leucopenia, 6-thioguanine nucleotide concentrations were extremely high [2211 pmol/(8 x 10 8 red blood cells)].1260)…”

Metabolism of azathioprine to 6‐thioguanine nucleotides in patients with pemphigus vulgaris.

“…6-Thioguanine nucleotides (6TGN) are the major thiopurine metabolites in the human red blood cell (RBC) . We have shown large individual variations in RBC 6TGN concentrations among patients on identical doses of azathioprine or 6-mercaptopurine (Lennard et al, , 1984a. Raised concentrations of RBC 6TGN have been found in patients with bone marrow depression due to azathioprine and 6-mercaptopurine (Lennard et al, 1984a,b).…”