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Influence of infusion method on gemcitabine pharmacokinetics: a controlled randomized multicenter trial

  • Clinical Trial Report
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Abstract

Purpose

Ensuring the correct administration of antineoplastic drugs is a constantly challenging task. Nowadays, several specific infusion devices have been marketed to decrease occupational exposure to these drugs through a post-administration rinsing step. As their impact on drug pharmacokinetics has never been evaluated, the objective of this study was to assess how the infusion process may alter the pharmacokinetics of antineoplastic drugs.

Methods

We developed a prospective randomized multicenter pharmacokinetic study (ONCOPERF01) to compare the influence of three infusion techniques (gravity-fed infusion—GFI, infusion pump—IP, and gravity-fed infusion with post-administration rinsing—PAR) to assess the impact of both flow rate and post-administration rinsing on gemcitabine pharmacokinetics during three consecutive administrations. Gemcitabine pharmacokinetics was determined with a two-compartment model after plasma dosing with an HPLC–UV method. Statistical comparisons of the three groups were made using repeated-measure analysis of variance (PROC MIXED).

Results

Patients received gemcitabine by gravity-fed infusion (GFI, n = 9; IP, n = 9; PAR, n = 7). Significant differences were noted between infusion duration (GFI = 30.0 ± 2.6 min, IP = 29.1 ± 1.2 min, PAR = 33.7 ± 3.5 min; p = 0.003) and AUCt (GFI = 23.5 ± 8.2 µM h, IP = 25.4 ± 9.1 µM h, PAR = 28.5 ± 6.3 µM h; p = 0.0009), which was significantly higher in the infusion group with post-administration rinsing than in the other groups.

Conclusions

The ONCOPERF01 study indicates that post-administration rinsing leads to a significant increase in patient exposure to gemcitabine, whereas controlling flow rate has no significance. Further surveys are required to assess the impact of such infusion techniques on other antineoplastic drugs.

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Acknowledgments

The authors thank DORAN International for sponsoring the Oncoperf01 study. The authors thank the different healthcare teams for their implication in the project, notably Ms. Charlotte Dujardin (CHRU de Lille) and Ms. Patricia Fossé (CHU de Rouen) for their help in recruiting patients and in managing the study. Doran International was implicated in this study for their financial support and kindly offered the infusion systems tested in the study. The scientific committee approved the protocol and all the amendments. This manuscript was written and approved by the authors.

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Authors and Affiliations

  1. Institut de Pharmacie, CHRU, Lille Cedex, France

    Nicolas Simon, Michèle Vasseur, Christine Barthélémy, Bertrand Décaudin & Pascal Odou

  2. Univ Lille, 59000, Lille Cedex, France

    Nicolas Simon, Michèle Vasseur, Christine Barthélémy, Bertrand Décaudin & Pascal Odou

  3. UDSL, EA 7365 GRITA, 59000, Lille Cedex, France

    Nicolas Simon, Michèle Vasseur, Christine Barthélémy, Bertrand Décaudin & Pascal Odou

  4. Service d’oncologie et de médecine interne, CHRU, Lille Cedex, France

    Olivier Romano & Mohamed Hebbar

  5. Service d’Hépatogastroentérologie, CHU, Rouen, France

    Pierre Michel

  6. UDSL, EA 2694, 59000, Lille Cedex, France

    Claire Pinçon

  7. Unité « Tumorigénèse et Résistance au traitement » , Inserm U908, Centre Oscar Lambret, Lille Cedex, France

    Nicole Lemahieu

  8. Faculté des Sciences Pharmaceutiques et Biologiques, Laboratoire de Biopharmacie, Pharmacie Galénique et Hospitalière, 3, rue du Professeur Laguesse, B.P. 83, 59006, Lille Cedex, France

    Nicolas Simon

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  1. Nicolas Simon
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  2. Olivier Romano
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  3. Pierre Michel
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  10. Pascal Odou
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Corresponding author

Correspondence to Nicolas Simon.

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Conflict of interest

The study was sponsored by Doran International (Toussieu, France), manufacturer of both KIS-1 and PCHIMX-1.

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Simon, N., Romano, O., Michel, P. et al. Influence of infusion method on gemcitabine pharmacokinetics: a controlled randomized multicenter trial. Cancer Chemother Pharmacol 76, 865–871 (2015). https://doi.org/10.1007/s00280-015-2819-3

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  • DOI: https://doi.org/10.1007/s00280-015-2819-3

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