Close Correlation of 1‐β‐D‐Arabinofuranosylcytosine 5′‐Triphosphate, an Intracellular Active Metabolite, to the Therapeutic Efficacy of N 4 ‐Behenoyl‐1‐β‐D‐arabinofuranosylcytosine Therapy for Acute Myelogenous Leukemia

N4 ‐Behenoyl‐l‐β‐D‐arabinofuranosylcytosine (BHAC), a prodrug of 1‐β ‐D‐arabinofuranosylcy‐tosine, is used effectively for the treatment of leukemia in Japan. BHAC therapy may be more effective if it is delivered in conjunction with monitoring of 1‐β ‐D‐arabinofuranosylcytosine 5′‐tri‐phosphate (ara‐CTP), the intracellular active metabolite of ara‐C derived from BHAC. However, previous monitoring methods for ara‐CTP were insufficiently sensitive. Here, using our new sensitive method, we evaluated the ara‐CTP pharmacokinetics in relation to the therapeutic response in 11 acute myelogenous leukemia patients who received a 2‐h infusion of BHAC (70 mg/m 2 ) in combination remission induction therapy. ara‐CTP could be monitored at levels under 1 μ M. BHAC maintained effective levels of plasma ara‐C and intracellular ara‐CTP for a longer time, even compared with historical values of high‐dose ara‐C. The area under the concentration‐time curve of ara‐CTP was significantly greater in the patients with complete remission than in the patients without response. This greater amount of ara‐CTP was attributed to the higher ara‐CTP concentrations achieved in the responding patients. There was no apparent difference of plasma ara‐C pharmacokinetics between the two groups. Thus, for the first tune, the ara‐CTP pharmacokinetics was evaluated in relation to the therapeutic effect of BHAC, and the importance of ara‐CTP was proven. Administration of optimal BHAC therapy may require monitoring of the ara‐CTP pharmacokinetics in each individual patient.