[Phase I study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate)]

Gan To Kagaku Ryoho. 1990 Nov;17(11):2213-9.
[Article in Japanese]

Abstract

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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • English Abstract
  • Multicenter Study

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Anorexia / chemically induced
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Arabinonucleotides / administration & dosage
  • Arabinonucleotides / adverse effects
  • Arabinonucleotides / therapeutic use*
  • Cytidine Monophosphate / administration & dosage
  • Cytidine Monophosphate / adverse effects
  • Cytidine Monophosphate / analogs & derivatives*
  • Cytidine Monophosphate / therapeutic use
  • Diarrhea / chemically induced
  • Drug Administration Schedule
  • Drug Evaluation
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy
  • Nausea / chemically induced
  • Vomiting / chemically induced

Substances

  • Antineoplastic Agents
  • Arabinonucleotides
  • 1-arabinofuranosylcytosine-5'-stearylphosphate
  • Cytidine Monophosphate