Journal article
Population pharmacokinetics of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (Triapine (R)) in cancer patients
Cancer chemotherapy and pharmacology, Vol.67(2), pp.393-400
02/01/2011
DOI: 10.1007/s00280-010-1331-z
PMCID: PMC3059107
PMID: 20440618
Abstract
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.
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.
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.
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.
Details
- Title: Subtitle
- Population pharmacokinetics of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (Triapine (R)) in cancer patients
- Creators
- Jill Kolesar - University of Wisconsin–MadisonRichard C. Brundage - University of MinnesotaMarcia Pomplun - University of Wisconsin–MadisonDona Alberti - University of Wisconsin–MadisonKyle Holen - University of Wisconsin–MadisonAnne Traynor - University of Wisconsin–MadisonPercy Ivy - National Institutes of HealthGeorge Wilding - University of Wisconsin–Madison
- Resource Type
- Journal article
- Publication Details
- Cancer chemotherapy and pharmacology, Vol.67(2), pp.393-400
- DOI
- 10.1007/s00280-010-1331-z
- PMID
- 20440618
- PMCID
- PMC3059107
- NLM abbreviation
- Cancer Chemother Pharmacol
- ISSN
- 0344-5704
- eISSN
- 1432-0843
- Publisher
- Springer Nature
- Number of pages
- 8
- Grant note
- 24XS090 / CTEP Translational Research Initiative UL1RR025011 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) U01CA062491 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) U01CA062491 / NCI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) American College of Clinical Pharmacy 1ULRR0 25011 / National Center for Research Resources, NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR)
- Language
- English
- Date published
- 02/01/2011
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984695798102771
Metrics
1 Record Views