PMID: 11320662Apr 26, 2001Paper

Plasma pharmacokinetics and cerebrospinal fluid penetration of thioguanine in children with acute lymphoblastic leukemia: a collaborative Pediatric Oncology Branch, NCI, and Children's Cancer Group study

Cancer Chemotherapy and Pharmacology
E S LowePeter C Adamson

Abstract

In preclinical studies, thioguanine (TG) has been shown to be more potent than the standard acute lymphoblastic leukemia (ALL) maintenance agent, mercaptopurine (MP), suggesting that TG may be more efficacious than MP in the treatment of childhood ALL. As part of a pilot trial in which TG was used in place of MP, we studied the plasma pharmacokinetics of oral TG and measured steady-state plasma and CSF TG concentrations during a continuous intravenous infusion (CIVI) in children with newly diagnosed standard-risk ALL. Nine plasma samples were collected after each patient's first 60 mg/m2 oral TG dose during maintenance. CIVI TG (20 mg/m2/h over 24 h) was administered during the consolidation phase of therapy, and simultaneous plasma and CSF samples were collected near the end of the infusion. TG was measured by reverse-phase HPLC with ultraviolet detection. Erythrocyte TG nucleotide (TGN) concentrations were measured 7 days after a course of CIVI TG and prior to the start of each maintenance cycle. After oral TG (n = 35), the mean (+/- SD) peak plasma concentration was 0.46 +/- 0.68 microM and the AUC ranged from 0.18 to 9.5 microM.h (mean 1.5 microM.h). Mean steady-state plasma and CSF TG concentrations during CIVI (n = 33) we...Continue Reading

Citations

Jul 29, 2003·Clinical Pharmacokinetics·Dirk Schrijvers
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May 13, 2011·The Journal of Law, Medicine & Ethics : a Journal of the American Society of Law, Medicine & Ethics·Katherine Drabiak-Syed
Feb 11, 2015·Journal of Clinical Epidemiology·Chia-Hsuin ChangYu-Kang Tu
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Jun 6, 2009·The Journal of Law, Medicine & Ethics : a Journal of the American Society of Law, Medicine & Ethics·Elizabeth Weeks Leonard
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Jul 17, 2019·Conservation Biology : the Journal of the Society for Conservation Biology·Katherine E MosebyJohn L Read
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May 6, 2019·Journal of Epidemiology and Community Health·Emelie BenyiLars Sävendahl
Jun 6, 2018·The Journal of Infectious Diseases·Liang LiYan Q Xiong
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