Mathematical modeling of topotecan pharmacokinetics and toxicodynamics in mice.

Mathematical modeling of topotecan pharmacokinetics and toxicodynamics in mice. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Mathematical modeling of topotecan pharmacokinetics and toxicodynamics in mice. Abstract Text:

Jin Chen,Qiang Lu,Joseph P Balthasar,Jin Chen,Qiang Lu,Joseph P Balthasar,Jin Chen,Qiang Lu,Joseph P Balthasar,

The objective of this study was to investigate the pharmacokinetics and toxicodynamics of topotecan (TPT) in mice and to develop an integrated pharmacokinetic/toxicodynamic (PK/TD) model to characterize the relationship between the time course of TPT disposition and the time course of TPT-induced toxicity. TPT was administered to groups of 3-5 mice via i.v. bolus injection, i.p. bolus injection, and by i.p. infusion over 24, 72 and 168 h. Body weight was monitored to assess TPT-induced toxicity, and serial blood samples were collected and analyzed via HPLC to assess TPT pharmacokinetics. We found that TPT-induced toxicity increased dose-dependently for each mode of dosing investigated. The time course of topotecan-induced body weight-loss was delayed relative to the time course of topotecan disposition; nadir body weight was observed as late as 6 days following i.p. bolus dosing, and 3-5 days following termination of i.p. infusion. TPT exhibited non-linear disposition, which was well-characterized through the use of a two-compartment model with saturable elimination from the central compartment. Toxicodynamic data were characterized with an integrated PK/TD model that incorporated an indirect-effect model and four transit compartments to describe transduction events associated with TPT-induced toxicity. This model will be used to support the development of an inverse-targeting strategy that aims to enhance topotecan safety and efficacy.

Mathematical modeling of topotecan pharmacokinetics and toxicodynamics in mice. Publishing Authors By Initials

J Chen,Q Lu,JP Balthasar,J Chen,Q Lu,JP Balthasar,J Chen,Q Lu,JP Balthasar,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Mathematical modeling of topotecan pharmacokinetics and toxicodynamics in mice. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of pharmacokinetics and pharmacodynamics

VOLUME: 34

Page Numbers: 829-47

Journal Abbreviation:

ISSN: 1567-567X

DAY: 21

MONTH: 09

YEAR: 2007

Mathematical modeling of topotecan pharmacokinetics and toxicodynamics in mice. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101096520

Mathematical modeling of topotecan pharmacokinetics and toxicodynamics in mice. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Mathematical modeling of topotecan pharmacokinetics and toxicodynamics in mice. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Mathematical modeling of topotecan pharmacokinetics and toxicodynamics in mice.

AFFILIATION: Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, 14260, USA, jb@acsu.buffalo.edu.

Country: England

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: J Pharmacokinet Pharmacodyn

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Mathematical modeling of topotecan pharmacokinetics and toxicodynamics in mice Related Publications

• Comparison of the effects of antibody-coated liposomes, IVIG, and anti-RBC immunotherapy in a murine model of passive chronic immune thrombocytopenia.
• Mathematical modeling of topotecan pharmacokinetics and toxicodynamics in mice.
• Pharmacokinetic/pharmacodynamic modeling of IVIG effects in a murine model of immune thrombocytopenia.
• Physiologically-based pharmacokinetic (PBPK) model to predict IgG tissue kinetics in wild-type and FcRn-knockout mice.