Calculation of individual dosage regimen of cytosine arabinoside (ara-C) based on metabolite levels in leukemic cells.
Patients with acute nonlymphocytic leukemia (ANLL) were treated by continuous infusion of ara-C (100 mg/m2/d x 10 days). During ara-C treatment, cellular arabinofuranosyl cytosine triphosphate (ara-CTP) pharmacokinetics was assessed in the circulating blasts of these patients using a high-performance liquid chromatography (HPLC) and an associated radioimmunoassay. Since a strong correlation was found between achievement of complete remission and cellular ara-CTP levels, we propose a calculation scheme that allows steady-state adjustment of ara-CTP levels during administration of ara-C. To improve the complete remission rate in patients with low ara-CTP levels, we sought optimum ara-C dosing. In order to achieve an optimal therapeutic response, in vivo ara-CTP formation has to be > 50 microM in leukemic cells. Conversely, using the same pharmacokinetic approach, the infusion rate at which to administer ara-C in order to reach in vivo ara-CTP concentration threshold and to achieve complete remission could be calculated for each patient.
Riva-Lavieille
C
C
Faculté de Pharmacie, Groupe de Recherche sur les Cancers des Voies Aériennes, Grenoble, France.
Ressayre
C
C
Barra
Y
Y
Carcassonne
Y
Y
Iliadis
A
A
D001085:Arabinofuranosylcytosine Triphosphate / Q000378:metabolism; D003561:Cytarabine / Q000008:administration & dosage* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*
D003561:Cytarabine; D001085:Arabinofuranosylcytosine Triphosphate