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Biliary elimination and pharmacokinetics of vinorelbine in micropigs

  • Short Communication
  • Vinorelbine, Pharmacokinetics, Biliary Elimination, Micropigs
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Abstract

The biliary elimination and pharmacokinetics of vinorelbine (NVB) were investigated in five conscious micropigs provided with a double-terminal choledocal fistula allowing the collection and reinstillation of bile. After the i. v. administration of NVB (0.5 mg/kg), serum and bile samples were collected over a 48-h period. The concentrations of NVB were measured by high-performance liquid chromatography. The serum concentrations decreased rapidly from a maximal value of 208.6 ng/ml (SD, 111.7 ng/ml). The mean half-life was 10.9h (SD, 8.6 h) and the mean AUC0–48h was 292.8 ng ml−1 h (SD, 79.4 ng ml−1 h). The bile concentrations were high, amounting to 16.0 μg/ml (range, 5.4–27.7 μg/ml). The 0- to 48-h biliary excretion of unchanged NVB accounted for 25.8% (SD, 5.7%) of the injected dose, with 21.5% (SD, 4.0%) being eliminated during the 0- to 8-h period. Desacetyl-NVB was found in an inconstant manner and in very low amounts in bile samples. In addition, no glucuronide of NVB could be detected. Thus, in the micropig, biliary excretion represents an important route of elimination for NVB.

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Abbreviations

NVB:

vinorelbine

HPLC:

high-performance liquid chromatography

t 1/2 :

terminal half-life

AUC:

area under the serum concentrations versus time curve

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Authors and Affiliations

  1. Laboratory of Pharmacokinetics, Institute of Bacteriology, 3 rue Koeberlé, F-67000, Strasbourg, France

    Dominique Levêque & François Jehl

  2. Laboratory of Biology and Pharmacokinetics, Paul Strauss Anticancer Center, 67 000, Strasbourg, France

    Jeannette Wihlm

  3. Department of Infectious Diseases, Hospital University Center, 54000, Nancy, France

    Myriam Merle-Melet

  4. Laboratory of Experimental Surgery, Hospital University Center, 54000, Nancy, France

    Laurent Bresler & Jean Paul Didelot

  5. Laboratory of Hematology, Hospital University Center, 54000, Nancy, France

    Jean Pierre Aymard

Authors
  1. Dominique Levêque
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  2. Myriam Merle-Melet
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  3. Laurent Bresler
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  4. Jean Paul Didelot
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  5. Jean Pierre Aymard
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  6. Jeannette Wihlm
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  7. François Jehl
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Levêque, D., Merle-Melet, M., Bresler, L. et al. Biliary elimination and pharmacokinetics of vinorelbine in micropigs. Cancer Chemother. Pharmacol. 32, 487–490 (1993). https://doi.org/10.1007/BF00685895

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  • DOI: https://doi.org/10.1007/BF00685895

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