Clinical pharmacology of oral thioguanine in acute myelogenous leukemia

Although thioguanine has been in clinical use for over 20 years, few data are yet available on the clinical pharmacology of thioguanine administered orally. We have studied the plasma thioguanine levels in acute myelogenous leukemia patients during remission induction (daunomycin 60 mg/m2 on day 1, arabinosylcytosine 200 mg/m 2. day for 7 days by infusion, thioguanine 100 mg/m2 PO every 12 h for 7 days) and remission maintenance (arabinosylcytosine 200 mg/m2 . day for 4 days by infusion, thioguanine 100 mg/m2 PO every 12 h for 4 days). Hourly blood samples were taken after thioguanine administration, and plasma thioguanine levels were measured by high-performance liquid chromatography with an anion-exchange column. Prior to the chromatography the thioguanine was oxidized by alkaline potassium permanganate to the corresponding 6-sulfonate, which was monitored by means of fluorescence detection. Peak plasma levels of thioguanine were observed 2-4 h after administration and varied from 0.03-0.94 microM. Plasma levels of thioguanine were markedly lower in patients with severe nausea and emesis. Food intake at the same time as thioguanine administration also tended to lower plasma drug levels. The 30-fold range in thioguanine plasma levels observed in this study suggests that intermittent IV administration may provide a better means of standardizing the dosage of thioguanine.