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The plasma of renal transplant patients was analyzed by high performance liquid chromatography (HPLC) for the presence of azathioprine and its primary metabolite, 6-mercaptopurine, after either oral or i.v. administration of azathioprine. Azathioprine was demonstrated in plasma at peak concentrations of 0.6 microgram/ml 15 min after i.v. injections of 100 to 200 mg. Within 90 min of injection, the azathioprine level fell to 10 ng/ml. Azathioprine was not detected in plasma at any time after an oral dose of 100 mg, indicating that the plasma concentration is less than 0.5 ng/ml, which is the sensitivity limit of this assay. 6-Mercaptopurine appeared in the plasma after either oral or i.v. azathioprine administration. Furthermore, decreased renal graft function has no effect on the rate of disappearance of azathioprine from plasma. These results demonstrate that high performance liquid chromatography can be used to determine azathioprine and 6-mercaptopurine levels in man, and that alteration in renal function does not influence early stages of azathioprine degradation.
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