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[Zhonghua Yan Ke Za Zhi] Chinese... Jul 1984
Topics: Adult; Ancitabine; Cytarabine; Female; Herpes Zoster Ophthalmicus; Humans; Male; Middle Aged
PubMed: 6210182
DOI: No ID Found -
Nihon Ketsueki Gakkai Zasshi : Journal... Jul 1984
Topics: Ancitabine; Animals; Antineoplastic Agents; Cytarabine; Kinetics; Mice; Structure-Activity Relationship
PubMed: 6209907
DOI: No ID Found -
[Rinsho Ketsueki] the Japanese Journal... Jul 1984
Topics: Acute Disease; Adolescent; Adult; Aged; Ancitabine; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine Monophosphate; Doxorubicin; Female; Humans; Leukemia; Male; Mercaptopurine; Middle Aged; Recurrence
PubMed: 6209434
DOI: No ID Found -
Journal of Pharmaceutical Sciences Jul 1984The kinetics of conversion of the prodrug ancitabine to the anticancer drug cytarabine have been studied in aqueous solutions in the pH range of 1.5-10.7, temperature...
The kinetics of conversion of the prodrug ancitabine to the anticancer drug cytarabine have been studied in aqueous solutions in the pH range of 1.5-10.7, temperature range of 19.5-80.0 degrees C, ionic strength range of 10(-4) to 1.5, and in the presence of several general-base catalysts. Under all conditions ancitabine was quantitatively converted to cytarabine. The pH-rate profiles were linear with slope = 1 in alkaline pH, becoming pH independent in the region of maximum stability at pH less than or equal to 4, where buffer catalysis was found to be insignificant and kobs approximately equal to (1.12 X 10(11) h-1)-exp [-10121 deg/T]. At 30 degrees C, pH less than or equal to 4, it is calculated that an aqueous ancitabine solution will maintain 90% of its initial concentration for 12 d. A novel method for measuring general-base catalysis in competition with predominating specific-base catalysis and in the presence of secondary salt effects at constant ionic strength was developed. Three mechanisms of hydrolytic prodrug conversion are proposed: nucleophilic hydroxide addition, general base-assisted nucleophilic water attack, and spontaneous water attack.
Topics: Ancitabine; Atmosphere; Catalysis; Chemistry, Pharmaceutical; Cytarabine; Drug Stability; Hydrochloric Acid; Hydrogen-Ion Concentration; Kinetics; Sodium Hydroxide; Spectrophotometry, Ultraviolet; Temperature
PubMed: 6206222
DOI: 10.1002/jps.2600730709 -
Journal of Pharmaceutical Sciences Jun 1984Conversion rates of the prodrug ancitabine to the antileukemic cytarabine have been measured in vivo (rabbits) and in vitro (in the presence of rabbit blood and human...
Conversion rates of the prodrug ancitabine to the antileukemic cytarabine have been measured in vivo (rabbits) and in vitro (in the presence of rabbit blood and human red blood cells, blood, and plasma) using HPLC analyses for the prodrug, drug, and its inactive metabolite, 1-beta-D-arabinosyluracil. These observed pH-dependent in vitro rate constants were consistent with those for chemical hydrolysis determined from controls using Tris buffers. Hydrolysis of ancitabine to cytarabine is chemically, not enzymatically, mediated. The blood concentration-time course for administered compound was described by a two-compartment open model following a rapid intravenous injection of prodrug, drug, or metabolite in each of three rabbits. The in vivo conversion rate constant (kc) following a rapid intravenous prodrug injection was estimated by simultaneous nonlinear regression of ancitabine and cytarabine blood concentration-time courses using equations for two-compartment prodrug and drug with all possible models describing potential conversion sites. The best fit was obtained for the case allowing simultaneous conversion of the prodrug in both central and peripheral compartments to the drug in the central compartment with a common value for kc. The resulting kc value (0.09 h-1, three rabbits) is similar to that for chemical hydrolysis (0.07 h-1) at 38.8 degrees C. Reasons why this agreement is regarded as fortuitous are discussed.
Topics: Ancitabine; Animals; Biotransformation; Cytarabine; Humans; Hydrogen-Ion Concentration; Hydrolysis; In Vitro Techniques; Injections, Intravenous; Kinetics; Male; Models, Biological; Rabbits; Spectrophotometry, Ultraviolet
PubMed: 6204036
DOI: 10.1002/jps.2600730606 -
Medical and Pediatric Oncology 1984A study of children in relapse with acute nonlymphocytic leukemia (ANLL) previously maintained in remission with combination chemotherapy including cytosine arabinoside... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Evaluation of cyclocytidine in reinduction and maintenance therapy of children with acute nonlymphocytic leukemia previously treated with cytosine arabinoside: a report from Children's Cancer Study Group.
A study of children in relapse with acute nonlymphocytic leukemia (ANLL) previously maintained in remission with combination chemotherapy including cytosine arabinoside (Ara-C) was undertaken by Children's Cancer Study Group (CCSG) to assess the efficacy of cyclocytidine (Cyclo-C), a depot Ara-C, compared to parenteral Ara-C given every 12 hr. The reinduction protocol consisted of daunomycin combined with either Ara-C (Regimen 1) or Cyclo-C (Regimen 2). One-hundred thirty eligible patients were entered on the randomized study. Hematologic toxicity was significant in both regimens and resulted in four drug-related deaths. Cardiac toxicity was observed in five patients, manifested only by abnormal echocardiogram or electrocardiogram patterns in three and congestive heart failure in two patients. Seventy-seven of 112 evaluable patients achieved M-1 or M-2A marrow remissions (69%): 46 of 60 on Regimen 1 (75%), 30 of 52 on Regimen 2 (60%). The remission rate between the two regimens was not significantly different. There was no significant difference in the duration of remission comparing maintenance cyclophosphamide combined with Ara-C or with Cyclo-C. Addition of VP-16 and CCNU to the maintenance therapy did not prolong the duration of remission. This study indicates that patients with childhood ANLL previously treated with Ara-C and daunomycin can obtain a successful second remission. A single daily subcutaneous dose of Cyclo-C was found to be as efficacious as Ara-C given intravenously every 12 hr. The single dose schedule provides a convenient way to treat patients with relapsed ANLL in the outpatient setting.
Topics: Adolescent; Adult; Ancitabine; Child; Child, Preschool; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Delayed-Action Preparations; Female; Humans; Infant; Injections, Intraperitoneal; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Lomustine; Male; Podophyllotoxin
PubMed: 6208468
DOI: 10.1002/mpo.2950120512 -
Gematologiia I Transfuziologiia 1984
Topics: Ancitabine; Animals; Cytarabine; Leukemia L1210; Liposomes; Mice
PubMed: 6203808
DOI: No ID Found -
Proceedings of the Society For... Jan 1984Cyclocytidine (CC), in addition to its antitumor properties, also causes copious flow of saliva. Calcium concentration of CC-evoked saliva from submaxillary (SM) and...
Cyclocytidine (CC), in addition to its antitumor properties, also causes copious flow of saliva. Calcium concentration of CC-evoked saliva from submaxillary (SM) and parotid (PA) glands of adult rats was initially 7 meq/liter and 15 meq/liter, respectively, and thus resembled that of sympathetically evoked secretion. From previous data, as well as present data, this is expected since CC apparently causes release of norepinephrine (NE) from adrenergic nerve endings. Present data also confirm that CC causes NE release since a single dose of reserpine (RES) (5 mg/kg), administered 24 hr prior to injection of CC in order to cause depletion of NE prevented the action of CC. Furthermore, the NE released by CC acts principally on beta-adrenergic receptors since propranolol administered prior to CC caused a marked reduction in flow and [Ca] of saliva, and prevented the usual CC-induced depletion of glandular calcium. An increase in [Ca] of SM but not PA gland was also caused by chronic (daily injections of 500 mg/kg body wt for 3 days) administration of CC. The same threefold increase was observed 2 days after injection of a single dose of CC also. The increase in glandular calcium was not prevented by propranolol, thus suggesting that this effect of CC on glandular [Ca] was probably not beta-mediated. The calcium increase may, however, be the result of depletion of NE. Thus, [Ca] of SM of CC-treated rats, that of RES-treated rats, and that of rats treated with RES + CC were very similar. If the mechanism of action of the two drugs were different (not NE depletion), the combined action of the two would have been additive.
Topics: Ancitabine; Animals; Calcium; Cytarabine; Female; Norepinephrine; Organ Size; Propranolol; Rats; Reserpine; Saliva; Salivary Glands; Time Factors
PubMed: 6198650
DOI: 10.3181/00379727-175-41758 -
Advances in Pharmacology and... 1984
Review
Topics: Acylation; Ancitabine; Animals; Antineoplastic Agents; Chemistry, Pharmaceutical; Cytarabine; Floxuridine; Fluorouracil; Humans; Phospholipids; Pyrimidines; Steroids; Tegafur
PubMed: 6085531
DOI: 10.1016/s1054-3589(08)60264-1 -
[Zhonghua Yan Ke Za Zhi] Chinese... Nov 1983
Topics: Adolescent; Adult; Ancitabine; Animals; Child; Child, Preschool; Cytarabine; Delayed-Action Preparations; Female; Humans; Infant; Keratitis, Dendritic; Male; Middle Aged; Rabbits
PubMed: 6202470
DOI: No ID Found