Intrathecal Administration of Cytosine Arabinoside (Ara-C) to Rhesus and Cynomolgus Monkeys

摘要

Cytosine Arabinoside (Ara-C) was administered by cisternal puncture to rhesus and cynomolgus monkeys on Monday and Thursday for up to four consecutive weeks. A dose-related response of muscle spasms, convulsions, and death was observed initially following the intrathecal administration of Ara-C at doses of 24, 48, 96, 192, and 384 mg/sq. m. This response is believed to be the direct result of the hyperacidity (pH 1.25 - 3.30) of the solutions and not the effect of the compound. The intrathecal injection of relatively neutral preparations of Ara-C to young adult monkeys appeared to be well tolerated clinically and hematologically at doses of 48 and 96 mg/sq. m. Moderate anorexia and weight loss, which was reversible upon discontinuation of Ara-C, were consistently seen at doses of 192 and 384 mg/sq. m. Doses of 770 mg/sq. m and greater produced occasional latent progressive paralysis of the hind limbs, generalized depression, anorexia, and death. (Author)