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Cisplatin Pharmacokinetics in Nontumoral Pig Liver Treated With Intravenous or Transarterial Hepatic Chemoembolization

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Abstract

Purpose

To evaluate cisplatin (CDDP) pharmacokinetics after its intravenous (IV) or intrahepatic arterial administration (IHA) in healthy pigs with or without embolization by absorbable gelatine.

Material and Methods

We analysed plasmatic and hepatic drug concentration in four groups of six mini-pigs each according to the modality of administration of CDDP (1 mg/kg): IV, IHA, IHA with partial embolization using absorbable gelatine (IHA-Pe), and IHA with complete embolization (IHA-Te). Unbounded plasmatic and hepatic platinum concentrations were measured. Concentration and pharmacokinetics parameters were compared using analysis of variance.

Results

For all groups, there was a rapid and biexponential decrease in free platinum concentration. Plasmatic terminal half-life (T1/2) was significantly decreased after embolization at 191, 178, 42, and 41 min after IV, IHA, IHA-Pe, and IHA-Te administration, respectively. Maximal plasmatic concentration and systemic exposure to CDDP (AUC24) values were significantly decreased after embolization (Cmax p = 0.0075; AUC24 p = 0.0053). Hepatic CDDP concentration rapidly peaked and then decreased progressively. After 24 h, the residual concentration represented 45, 47, 60, and 63 % of Cmax, respectively, after IV, IHA, IHA-Pe, and IHA-Te. Hepatic T1/2 and AUC∞ values were increased after embolization, but the differences were not statistically significant.

Conclusion

This preliminary study confirms the feasibility of a pig model to study systemic and hepatic CDDP pharmacokinetics. Systemic exposure is lower after embolization, which could minimize systemic toxicity. Hepatic T1/2 elimination and hepatic exposition values are increased with IHA compared with IV administration.

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Acknowledgments

We thank Sylvie Massoulier, Carine Nicolas, and Denis Gourcy for their contributions during the experiment.

Conflict of interest

All the authors declared that they have no conflict of interest.

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Authors and Affiliations

  1. Pôle de Radiologie, CHU Clermont-Ferrand, 58 Rue Montalembert, 63000, Clermont-Ferrand, France

    Pascal Chabrot, Lucie Cassagnes & Louis Boyer

  2. ISIT, UMR CNRS 6284, Université d’Auvergne Clermont 1, Faculté de Médecine, Place Henri Dunant, 63000, Clermont-Ferrand, France

    Pascal Chabrot, Lucie Cassagnes, Louis Boyer & Armand Abergel

  3. Service de Biopharmacie, Université d’Auvergne Clermont 1, Faculté de Pharmacie, Place Henri Dunant, 63000, Clermont-Ferrand, France

    Jean-Michel Cardot

  4. Pôle Digestif et Hépato-Biliaire, CHU Clermont-Ferrand, 1 Place Lucie Aubrac, 63100, Clermont-Ferrand, France

    Pierre Guibert, François Bouculat, Emmanuel Buc, Gilles Bommelaer & Armand Abergel

  5. Service de Biologie, Centre Jean Perrin, 58 Rue Montalembert, 63000, Clermont-Ferrand, France

    Anne Léger-Enreille

  6. Service d’Anatomie-Pathologique, CHU Clermont-Ferrand, 1 Place Lucie Aubrac, 63100, Clermont-Ferrand, France

    Pierre Dechelotte

Authors
  1. Pascal Chabrot
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  2. Jean-Michel Cardot
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  3. Pierre Guibert
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  4. François Bouculat
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  5. Lucie Cassagnes
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  6. Anne Léger-Enreille
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  7. Emmanuel Buc
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  8. Pierre Dechelotte
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  9. Gilles Bommelaer
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  10. Louis Boyer
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  11. Armand Abergel
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Corresponding author

Correspondence to Pascal Chabrot.

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Chabrot, P., Cardot, JM., Guibert, P. et al. Cisplatin Pharmacokinetics in Nontumoral Pig Liver Treated With Intravenous or Transarterial Hepatic Chemoembolization. Cardiovasc Intervent Radiol 35, 1467–1474 (2012). https://doi.org/10.1007/s00270-012-0386-0

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  • DOI: https://doi.org/10.1007/s00270-012-0386-0

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