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Pharmacokinetics of 1-ß-D-Arabinofuranosylcytosine in Humans¹

Clinical Pharmacology-Toxicology Center, Departments of Medicine [W. E. L.] and Pharmacology, Divisions of Clinical Pharmacology [S. H. W., D. H., D. L. A.] and Oncology [B. H.], University of Kansas Medical Center, Kansas City, Kansas 66103

The pharmacokinetics of 1-ß-D-arabinofuranosylcytosine (ara-C) in humans following rapid i.v. administration and slow i.v. infusion is reported, as is a high-pressure liquid chromatographic method for ara-C determination in biological fluids. Plasma concentrations of ara-C following a single i.v. dose of 100 mg had a biphasic decline with a mean terminal half-life of 2.62 hr. The half-life following a 4- to 5-day infusion was 2.47 hr. ara-C is rapidly deaminated to 1-ß-D-arabinofuranosyluracil. The ratio of ara-C to 1-ß-D-arabinofuranosyluracil excreted in urine in 48 hr was 1:4 after infusion and 1:6 after rapid injection. Most of the ara-C was excreted with in 5 hr. Total drug and metabolite excretion was 70% in 48 hr. ara-C infusion was administered according to a Southwest Oncology Group treatment protocol in which the loading dose was one-fourth of the infusion dose over 4 hr. With this treatment schedule, minimum steady-state plasma concentrations were not achieved in most patients by 4 hr. In order to reach plasma concentrations rapidly, a schedule of a loading dose 3 times the hourly infusion rate is suggested.

¹ Supported in part by Contract NCI-C-71-2184 and grants GM 15956 and CA 12644 from the USPHS.

² Postdoctoral trainee in Clinical Pharmacology (GM 01342).

Received 6/15/73. Accepted 11/ 7/73.