Abstract
The combination of high-dose cytarabine (ara-C) and amsacrine (m-AMSA) is effective treatment for relapsed adult acute leukemia. Studies were performed to determine if m-AMSA affected the pharmacokinetics of the active triphosphate ara-CTP in HL-60 and K562 cells in culture. No significant differences were observed in accumulation, rate of elimination, or total intracellular exposure to ara-CTP in cultures treated with 100 μM ara-C alone or in combination with 1 μM m-AMSA. In clinical investigations, the accumulation and retention of ara-CTP in circulating leukemic cells were studied in five patients after two serial doses of ara-C (3 g/m2 infused over 2 hours) and in six additional patients in whom the second dose of ara-C was accompanied by an infusion of m-AMSA (30 mg/m2 infused over 1 hour). While substantial differences were observed in the cellular pharmacokinetics of ara-CTP among patients, the rate of ara-CTP elimination and the total intracellular exposure to ara-CTP in individuals were remarkably similar after each ara-C infusion. Infusion of m-AMSA with the second dose of ara-C did not significantly affect the cellular pharmacokinetics of ara-CTP. These studies demonstrate the feasibility and utility of conducting investigations of the cellular pharmacology of drug-drug interactions in human leukemic cells during therapy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 479-483 |
| Number of pages | 5 |
| Journal | Cancer Treatment Reports |
| Volume | 71 |
| Issue number | 5 |
| State | Published - 1987 |
ASJC Scopus subject areas
- Oncology
- Cancer Research