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Safety and pharmacokinetics of intrathecal administration of pemetrexed in rats

DC FieldValueLanguage
dc.contributor.author정재용-
dc.date.accessioned2014-12-20T16:49:49Z-
dc.date.available2014-12-20T16:49:49Z-
dc.date.issued2011-
dc.identifier.issn0344-5704-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/93458-
dc.description.abstractPURPOSE: Leptomeningeal carcinomatosis is a devastating complication of malignant disease. In this study, we evaluated the safety and pharmacokinetics of intrathecally administered pemetrexed in rats. METHODS: Three levels of pemetrexed (0.3, 1, and 3 mg/kg) were administered to 15 rats per level (45 rats in total) twice a week for 2 weeks through specifically designed indwelling subarachnoid catheters. Presence of clinical and pathological neurotoxicity was evaluated. To evaluate the pharmacokinetics of pemetrexed, independent cohorts of 30 rats were treated with 1 mg/kg of pemetrexed and its concentration in cerebrospinal fluid (CSF) and blood was measured using UPLC/MS/MS. RESULTS: There were no cases of clinical or pathologic neurotoxicity after intrathecal administrations of pemetrexed at levels of 0.3 and 1 mg/kg; however, 5 of 15 (33%) rats died after administration of 3 mg/kg pemetrexed. The distribution/elimination of pemetrexed in CSF was best described by a two-compartment model, with initial and terminal half-lives of 0.43 and 1.43 h, respectively. The predicted maximal concentration in CSF was 588 μM, and high levels of pemetrexed appeared to be maintained for a long time. Area under the curve and volume of distribution at steady state were 560 μM h and 1.14 ml, respectively. CONCLUSIONS: The no observed adverse effect level of intrathecal administration of pemetrexed was 1 mg/kg in rats. At this level, therapeutically high and durable pemetrexed concentrations could be achieved. Based on these results, further research on intrathecal pemetrexed in humans or non-human primates should be considered.-
dc.description.statementOfResponsibilityopen-
dc.format.extent531~538-
dc.relation.isPartOfCancer Chemotherapy and Pharmacology-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleSafety and pharmacokinetics of intrathecal administration of pemetrexed in rats-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Pharmacology (약리학)-
dc.contributor.googleauthorJong-Mu Sun-
dc.contributor.googleauthorMi Hyun Nam-
dc.contributor.googleauthorJae Yong Chung-
dc.contributor.googleauthorBohee Im-
dc.contributor.googleauthorSoo-Youn Lee-
dc.contributor.googleauthorYoun-Lim Suh-
dc.contributor.googleauthorJin Seok Ahn-
dc.contributor.googleauthorKeunchil Park-
dc.contributor.googleauthorMyung-Ju Ahn-
dc.identifier.doi10.1007/s00280-010-1522-7-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA03709-
dc.relation.journalcodeJ00437-
dc.identifier.urlhttp://link.springer.com/article/10.1007%2Fs00280-010-1522-7-
dc.contributor.alternativeNameChung, Jae Yong-
dc.contributor.affiliatedAuthorChung, Jae Yong-
dc.rights.accessRightsnot free-
dc.citation.volume68-
dc.citation.number2-
dc.citation.startPage531-
dc.citation.endPage538-
dc.identifier.bibliographicCitationCancer Chemotherapy and Pharmacology, Vol.68(2) : 531-538, 2011-
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실)

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