Clinical pharmacology of arabinofuranosyladenine in combination with deoxycoformycin
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- Major, P.P., Agarwal, R.P. & Kufe, D.W. Cancer Chemother. Pharmacol. (1983) 10: 125. doi:10.1007/BF00446224
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We have administered five courses of arabinofuranosyladenine (ara-A) and deoxycoformycin (DCF) to two patients and have studied the effects of DCF on the pharmacokinetics of ara-A. Ara-A was given by IV infusion over 3 h at a dose of 300 mg/m2/day for 3 days on the first two courses of treatment for each patient. One patient received a third course at a dose of 300 mg/m2/day every 12 h for 3 days. During the first course of treatment, patients received DCF (10 mg/m2) 60 min prior to the ara-A infusion on days 2 and 3 only. However, during subsequent courses, DCF was administered on each of the 3 days. On day 1 of the first course of treatment ara-A was not detectable in the plasma, while ara-hypoxanthine (ara-hyp) reached levels of up to 12.0 μg/ml. On day 2, DCF pretreatment resulted in detectable ara-A levels and decreased ara-hyp. On day 3, the levels of ara-A increased further and ara-hyp was no longer detectable. On subsequent courses, the administration of DCF on each of the 3 days of treatment resulted in detectable ara-A levels on day 1, with progressive increases on days 2 and 3. During the second course of treatment, increases in the excretion half-life of ara-A were noted during the 3-day treatment schedule, with values increasing from 258.2 min to 546 min and from 77.3 min to 219 min for patients I and II, respectively. Peak CSF ara-A levels were approximately one-third of peak plasma levels. No toxicity was encountered in patients treated at these doses of ara-A and DCF. Abrupt declines in peripheral blast counts were observed in each patient.