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Pharmaceutical Research

, Volume 23, Issue 9, pp 2030–2035 | Cite as

Predicting Plutonium Decorporation Efficacy after Intravenous Administration of DTPA Formulations: Study of Pharmacokinetic–Pharmacodynamic Relationships in Rats

  • Guillaume Phan
  • Béatrice Le Gall
  • Jean-Robert Deverre
  • Elias Fattal
  • Henri Bénech
Research Paper

Abstract

Purpose

The objectives of this study were: 1) to assess the relationship between plutonium decorporation (increased excretion and reduced retention in main organs of deposition) induced by intravenous liposome formulations of the chelating agent diethylene triamine pentaacetic acid (DTPA) and its pharmacokinetics, and 2) to model the renal excretion of plutonium after treatment with liposome-encapsulated DTPA in order to predict its efficacy and to optimise treatment schedules.

Materials and Methods

Pharmacokinetic parameters from plasma or urinary data (days 0–16 sample collections) were modelled versus decorporation efficacy, and best correlations were selected for their goodness of fit.

Results

The plutonium decorporation enhancement by DTPA liposomal formulations was well described by logistic models and the best correlation was observed with the area under the DTPA concentration curve of each formulation. The plutonium urinary excretion rates decreased mono-exponentially as a function of time after a single dose and the proposed model allowed a simple determination of the elimination half-life of the Pu–DTPA complex, a reasonably good approximation of the long-term efficacy of the treatments from truncated urinary data.

Conclusions

Both liposomal formulations of chelating agents and pharmacokinetic approaches to plutonium decorporation should be helpful in optimising treatment protocols.

Key words

DTPA excretion rate liposome PK/PD correlation plutonium decorporation 

Abbreviations

C-MLV

conventional multilamellar vesicle

CL

conventional liposome

CL-100 nm

conventional liposome sized at around 100 nm

DTPA

diethylene triamine pentaacetic acid

IA

injected activity

MLV

multi-lamellar vesicle

Pu

plutonium

S-MLV

stealth multi-lamellar vesicle

SL

sterically stabilized (Stealth®) liposome

SL-100 nm

stealth liposome sized at around 100 nm

Notes

Acknowledgment

The authors acknowledge the scientific committee of the Nuclear Toxicology Programme of the CEA, France for funding.

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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Guillaume Phan
    • 1
  • Béatrice Le Gall
    • 2
  • Jean-Robert Deverre
    • 3
  • Elias Fattal
    • 4
  • Henri Bénech
    • 1
  1. 1.CEAService de Pharmacologie et d'ImmunologieGif-sur-YvetteFrance
  2. 2.CEALaboratoire de Radio-ToxicologieBruyères-le-ChâtelFrance
  3. 3.CEAService Hospitalier Frédéric JoliotOrsayFrance
  4. 4.Laboratoire de Physico-chimie Pharmacotechnie et BiopharmacieChâtenay-MalabryFrance

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