| Population pharmacokinetics of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (Triapine®) in cancer patients. | |
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MedLine Citation:
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PMID: 20440618 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: The purpose of this study was to develop a population pharmacokinetic (PK) model for 3-AP, to evaluate the effect of ABCB1 polymorphisms on the pharmacokinetic profile of 3-AP, and to assess the relationship between 3AP disposition and patient covariates. METHODS: A total of 40 patients with advanced cancer from two phase 1 studies were included in the population PK model building. Patients received 3-AP 25-105 mg/m(2) IV on day 1. 3-AP plasma and erythrocyte levels were sampled at 10 timepoints over a 24-h period and measured by a validated HPLC method. Data were analyzed by a nonlinear mixed-effects modeling approach using the NONMEM system. RESULTS: 3-AP pharmacokinetics were described as a 3-compartment model with first-order elimination, with one compartment representing the plasma and another representing erythrocyte concentrations. Gender was associated with volume of distribution, in which women had a lower V2. The number of cycles administered was associated with clearance; those with decreased clearance were more likely to receive less than 2 cycles before going off study. CONCLUSION: This study suggests that monitoring 3-AP plasma concentrations in the first cycle and dose adjustment in those with decreased clearance may be helpful in decreasing toxicity associated with the 3-AP. |
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Authors:
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Jill Kolesar; Richard C Brundage; Marcia Pomplun; Dona Alberti; Kyle Holen; Anne Traynor; Percy Ivy; George Wilding |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-05-04 |
Journal Detail:
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Title: Cancer chemotherapy and pharmacology Volume: 67 ISSN: 1432-0843 ISO Abbreviation: Cancer Chemother. Pharmacol. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-28 Completed Date: 2011-04-11 Revised Date: 2013-05-29 |
Medline Journal Info:
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Nlm Unique ID: 7806519 Medline TA: Cancer Chemother Pharmacol Country: Germany |
Other Details:
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Languages: eng Pagination: 393-400 Citation Subset: IM |
Affiliation:
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Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin, 600 Highland Avenue, K4/554, Madison, WI 53792, USA. jmkolesar@pharmacy.wisc.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aged, 80 and over Blood / metabolism Body Surface Area Clinical Trials, Phase I as Topic Computer Simulation Erythrocytes / metabolism Female Genotype Humans Male Metabolic Clearance Rate Middle Aged Models, Biological* Models, Statistical Neoplasms / drug therapy, metabolism* P-Glycoprotein / genetics Pyridines / administration & dosage, blood, metabolism, pharmacokinetics* Sex Characteristics Thiosemicarbazones / administration & dosage, blood, metabolism, pharmacokinetics* |
| Grant Support | |
ID/Acronym/Agency:
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1ULRR025011//PHS HHS; U01 CA062491-06/CA/NCI NIH HHS; U01 CA062491-07/CA/NCI NIH HHS; U01 CA062491-07S1/CA/NCI NIH HHS; U01 CA062491-07S2/CA/NCI NIH HHS; U01 CA062491-08/CA/NCI NIH HHS; U01 CA062491-09/CA/NCI NIH HHS; U01 CA062491-10/CA/NCI NIH HHS; U01 CA062491-11/CA/NCI NIH HHS; U01 CA062491-12/CA/NCI NIH HHS; U01 CA062491-13/CA/NCI NIH HHS; U01 CA062491-14/CA/NCI NIH HHS; U01 CA062491-15/CA/NCI NIH HHS; U01 CA062491-16/CA/NCI NIH HHS; U01 CA062491-17/CA/NCI NIH HHS; U01 CA062491-18/CA/NCI NIH HHS; U01CA062491/CA/NCI NIH HHS; UL1 RR025011-01/RR/NCRR NIH HHS; UL1 RR025011-02/RR/NCRR NIH HHS; UL1 RR025011-03/RR/NCRR NIH HHS; UL1 RR025011-03S1/RR/NCRR NIH HHS; UL1 RR025011-03S2/RR/NCRR NIH HHS; UL1 RR025011-04/RR/NCRR NIH HHS; UL1 RR025011-05/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/ABCB1 protein, human; 0/P-Glycoprotein; 0/Pyridines; 0/Thiosemicarbazones; 143621-35-6/3-aminopyridine-2-carboxaldehyde thiosemicarbazone |
| Comments/Corrections | |
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