[Phase I study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate)].
Phase I study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate), a derivative of cytosine arabinoside (Ara-C), was conducted by cooperative study groups between January 1986 and June 1987. The dosage for the single and 5-day oral administration ranged 50 to 1,200 and 100 to 900 mg/body/day, respectively. The main adverse effects were myelo-suppression and gastrointestinal toxicities such as nausea, vomiting, anorexia and diarrhea. In the single administration, the maximum tolerated dose (MTD) could not be determined, however, in the 5-day schedule MTD was considered to be 700 to 900 mg/body/day, and the dose limiting factor to be thrombocytopenia. After the single administration (800 mg/body/day) of YNK01, the plasma concentration of Ara-C, an active metabolite of YNK01, was 3.43 ng/ml (Cmax) at 24 hrs. and 0.82 ng/ml at 72 hrs. During the 5-day administration for 300 mg/body/day and 500 mg/body/day, the Ara-C concentration changed from 2.3 to 4.1 ng/ml, and from 1.5 to 11.9 ng/ml respectively, and sustained almost the same concentration as to during the administration period until the 2nd day after the completion of the administration.
Fukuoka
M
M
Osaka Prefectural Habikino Hospital.
Miyazaki
T
T
Yoshida
Y
Y
Hattori
M
M
Niitani
H
H
Nakamura
T
T
Hirota
Y
Y
Ohta
K
K
Tanaka
M
M
Suzuoki
Y
Y
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000855:Anorexia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001088:Arabinonucleotides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003568:Cytidine Monophosphate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy; D009325:Nausea / Q000139:chemically induced; D014839:Vomiting / Q000139:chemically induced
D000970:Antineoplastic Agents; D001088:Arabinonucleotides; C061162:1-arabinofuranosylcytosine-5'-stearylphosphate; D003568:Cytidine Monophosphate