{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:21:23Z","timestamp":1790972483032,"version":"4.1.0"},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[1983,12]]},"abstract":"<jats:p> The pharmacokinetics of high-dose cytosine arabinoside (HiDAC) given as a three-hour intravenous infusion at 3 g\/m2 were studied in five patients with acute leukemia during relapse and\/or remission of their disease. Apparent steady state plasma levels of ara-C during 13 infusions averaged 115 +\/- 32 microM. Upon cessation of the infusion, cytosine arabinoside (ara-C) was rapidly cleared from the plasma. The apparent postinfusion kinetics of ara-C were triexponential with a distribution half-life of 16 minutes and elimination half-lives of 1.8 hours and six hours. Total clearance averaged 86 L per hour and mean residence time averaged 0.47 hours. Disease status (relapse or remission) had no apparent effect on the pharmacokinetic characteristics of ara-C. Peak levels of ara-U averaged 310 microM and the metabolite had an average apparent elimination half-life of 3.75 hours. Despite the persistence of ara-U at about 100 microM at the time of administration of subsequent infusions of ara-C, there was no further accumulation of ara-U in the plasma with repetitive infusions of HiDAC. In vitro studies indicate that ara-U can exert an inhibitory effect on deoxycytidine (dCyd) deaminase activity. The ratio of the Ki of ara-U to the Km of ara-C for cytidine (Cyd)-dCyd deaminase is 40:1; however, during the gamma phase of ara-C elimination, the ratio of ara-U:ara-C in plasma is at least 100:1. Thus, a retardation of systemic catabolism of ara-C by ara-U is possible. Two to three hours after the termination of the HiDAC infusion, the ara-C cerebrospinal fluid: plasma ratio is 1-3:1, a feature of potential therapeutic significance. The slower elimination of ara-C from the CSF may also contribute to the plasma gamma half-life. <\/jats:p>","DOI":"10.1200\/jco.1983.1.12.763","type":"journal-article","created":{"date-parts":[[2017,2,23]],"date-time":"2017-02-23T12:56:51Z","timestamp":1487854611000},"page":"763-771","source":"Crossref","is-referenced-by-count":90,"title":["Alteration of the pharmacokinetics of high-dose ara-C by its metabolite, high ara-U in patients with acute leukemia."],"prefix":"10.1200","volume":"1","author":[{"given":"R L","family":"Capizzi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J L","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Bjornsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Sahasrabudhe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R S","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y C","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.1983.1.12.763","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T19:53:09Z","timestamp":1653508389000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.1983.1.12.763"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1983,12]]},"references-count":0,"journal-issue":{"issue":"12","published-print":{"date-parts":[[1983,12]]}},"alternative-id":["10.1200\/JCO.1983.1.12.763"],"URL":"https:\/\/doi.org\/10.1200\/jco.1983.1.12.763","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[1983,12]]}}}