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Determination of the in vivo pharmacokinetics of palladium-bacteriopheophorbide (WST09) in EMT6 tumour-bearing Balb/c mice using graphite furnace atomic absorption spectroscopy

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Abstract

Palladium-bacteriopheophorbide (WST09), a novel bacteriochlorophyll derivative, is currently being investigated for use as a photodynamic therapy (PDT) drug due to its strong absorption in the near-infrared region and its ability to efficiently generate singlet oxygen when irradiated. In this study, we determined the pharmacokinetics and tissue distribution of WST09 in female EMT6 tumour-bearing Balb/c mice in order to determine if selective accumulation of this drug occurs in tumour tissue. A total of 41 mice were administered WST09 by bolus injection into the tail vein at a dose level of 5.0 ± 0.8 mg kg−1. Three to six mice were sacrificed at each of 0.08, 0.25, 0.5, 1.0, 3.0, 6.0, 9.0, 12, 24, 48, 72, and 96 h post injection, and an additional three control mice were sacrificed without having been administered WST09. Terminal blood samples as well as liver, skin, muscle, kidney and tumour samples were obtained from each mouse and analyzed for palladium content (from WST09) using graphite furnace atomic absorption spectroscopy (GFAAS). The representative concentration of WST09 in the plasma and tissues was then calculated. Biphasic kinetics were observed in the plasma, kidney, and liver with clearance from each of these tissues being relatively rapid. Skin, muscle and tumour did not show any significant accumulation at all time points investigated. No selective drug accumulation was seen in the tumour and normal tissues, relative to plasma. Thus the results of this study indicate that vascular targeting resulting from WST09 in the circulation, as opposed to selective WST09 accumulation in tumour tissues, may be responsible for PDT effects in tumours that have been observed in other WST09 studies.

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Abbreviations

GFAAS:

graphite furnace atomic absorption spectroscopy

WSTO9/TOOKAD:

palladium-bacteriopheophorbide

PDT:

photodynamic therapy

AUC0−tlast:

area under the drug concentration vs. time plot from 0 h to the last quantifiable value

AUC0−∞:

area under the drug concentration vs. time plot from 0 h to infinity

Cl:

rate of total clearance of the drug

Cmax:

highest drug concentrationmeasured following administration

kα:

drug distribution rate constant

kβ:

drug elimination rate constant

t1/2α:

drug distribution half-life

t1/2β:

drug elimination half-life

tmax:

time at which the highest drug concentration is measured following administration

Vd:

apparent volume of initial drug distribution

IR:

infrared

UV-Vis:

ultraviolet-visible

HPLC:

high pressure liquid chromatography

rpm:

revolutions per minute

HDL:

high density lipoproteins

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Authors and Affiliations

  1. Steba Biotech, Avenue de l’Europe, Toussus-le-Noble, Magny-les-Hameaux, Cedex, France, 78771

    Pierre Hervé Brun

  2. Department of Chemistry and Chemical Engineering, The Royal Military College of Canada, PO Box 17000, Station Forces, Kingston, Ontario, Canada, K7K 7B4

    Jennifer L. De Groot, Eva F. Gudgin Dickson, Mohsen Farahani & Roy H. Pottier

Authors
  1. Pierre Hervé Brun
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  2. Jennifer L. De Groot
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  3. Eva F. Gudgin Dickson
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  4. Mohsen Farahani
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  5. Roy H. Pottier
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Corresponding author

Correspondence to Eva F. Gudgin Dickson.

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Brun, P.H., De Groot, J.L., Gudgin Dickson, E.F. et al. Determination of the in vivo pharmacokinetics of palladium-bacteriopheophorbide (WST09) in EMT6 tumour-bearing Balb/c mice using graphite furnace atomic absorption spectroscopy. Photochem Photobiol Sci 3, 1006–1010 (2004). https://doi.org/10.1039/b403534h

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