Clincal pharmacology of O2,2'-cyclocytidine.
Two metabolites of 2-14C-cyclocytidine (cyclo-C) were found in the plasma and urine and a hydrolytic product, arabinosylcytosine (ara-C), and its deaminated product, arabinosyluracil (ara-U), were found in patients with cancer; 80% of the dose was found in urine in 24 hr, 70% as cyclo-C and 10% as ara-C and ara-U. The plasma disappearance curve of ara-C curvilinear; the half-life of ara-C estimated from the terminal phase is 8 hr. By 6 hr, the ara-C level is 0.35 mug/ml and falls exponentially to 0.006 mug/ml by 24 hr. Plasma concentration ratios of ara-U to ara-C are 0.1 to 0.3, 0.3 to 0.4, and 1.1 to 1.3 at 10 min, 1 hr, and 4 hr following intravenous injection of cyclo-C at 200 mg/m2. Five min after an equal dose of ara-C, this ratio is approximately 2, and by 4 hr, plasma ara-C levels are immeasurable. After intramuscular and subcutaneous administration, cyclo-C is rapidly absorbed. The plasma disappearance curves of the cyclo-C hydrolytic product, ara-C, are similar to those of the intravenous route. Intramuscularly, subcutaneously, and intravenously cyclo-C should be equally effective. Intrathecal injections of cyclo-C (50 mg/m2) result in an effective ara-C level (0.1 mug/ml) in cerebrospinal fluid (CSF) at 24 hr. When cyclo-C is given orally to fasting patients, less than 15% of the dose is excreted in urine in 24 hr and none can be detected in the plasma.
D000284:Administration, Oral; D000812:Anhydrides / Q000008:administration & dosage / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003641:Deamination; D006207:Half-Life; D006801:Humans; D006868:Hydrolysis; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D007938:Leukemia / Q000188:drug therapy*; D009369:Neoplasms / Q000188:drug therapy*; D013997:Time Factors
D000812:Anhydrides; D000970:Antineoplastic Agents; D003561:Cytarabine