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Pharmacologic studies of continuous infusion of arabinosylcytosine by liquid infusion system

Arabinosylcytosine (ara‐C) was administered by prolonged intravenous infusion with a portable liquid infusion system (LIS) to patients with acute myelogenous leukemia. With the use of tritiated ara‐C and this portable system, pharmacologic studies were performed in 8 patients. Most of the plasma radioactivity is in the deaminated product, arabinosyluracil (ara‐U). After continuous intravenous irifusion, a constant ara‐C level is achieved slowly in the plasma. Unless a loading (priming) dose is administered immediately before beginning the irifusion, a steady‐state ara‐C level cannot be achieved until 8 to 24 hr after the infusion. The infusion system has two mechanisms‐one for giving a loading dose (3 mllmin) and the other for regular infusion at a rate of 0.5 to 2.0 m!lhr. If a loading dose is given before continuous infusion, a steady‐state ara‐C level is achieved within an hour. The plasma ara‐C disappearance curves are biphasic with a terminal half‐life of 104 min, which is the same as that of a single injection. The cumulative urinary excretion after approximately 23 hr of infusion varied from 14% to 35% in different patients; more than 90% is ara‐U and the remainder is ara‐C. Our results have demonstrated that LIS can be used conveniently to sustain a constant plasma level of ara‐C. The LIS increases mobility of both inpatients and outpatients and is particularly convenient for ambulatory patients.