title: Influence of infusion method on gemcitabine pharmacokinetics: a controlled randomized multicenter trial.
abstract: OBJECTIVE
  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.
authors.affiliation: Institut de Pharmacie, CHRU, Lille Cedex, France. nicolas.simon@univ-lille2.fr.|Univ Lille, 59000, Lille Cedex, France. nicolas.simon@univ-lille2.fr.|UDSL, EA 7365 GRITA, 59000, Lille Cedex, France. nicolas.simon@univ-lille2.fr.|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@univ-lille2.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Simon
authors.affiliation: Service d'oncologie et de médecine interne, CHRU, Lille Cedex, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Romano
authors.affiliation: Service d'Hépatogastroentérologie, CHU, Rouen, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Michel
authors.affiliation: UDSL, EA 2694, 59000, Lille Cedex, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Pinçon
authors.affiliation: Institut de Pharmacie, CHRU, Lille Cedex, France.|Univ Lille, 59000, Lille Cedex, France.|UDSL, EA 7365 GRITA, 59000, Lille Cedex, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Vasseur
authors.affiliation: Unité « Tumorigénèse et Résistance au traitement » , Inserm U908, Centre Oscar Lambret, Lille Cedex, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Lemahieu
authors.affiliation: Institut de Pharmacie, CHRU, Lille Cedex, France.|Univ Lille, 59000, Lille Cedex, France.|UDSL, EA 7365 GRITA, 59000, Lille Cedex, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Barthélémy
authors.affiliation: Service d'oncologie et de médecine interne, CHRU, Lille Cedex, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hebbar
authors.affiliation: Institut de Pharmacie, CHRU, Lille Cedex, France.|Univ Lille, 59000, Lille Cedex, France.|UDSL, EA 7365 GRITA, 59000, Lille Cedex, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Décaudin
authors.affiliation: Institut de Pharmacie, CHRU, Lille Cedex, France.|Univ Lille, 59000, Lille Cedex, France.|UDSL, EA 7365 GRITA, 59000, Lille Cedex, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Odou
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006207:Half-Life; D006801:Humans; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D016273:Occupational Exposure / Q000517:prevention & control; D012965:Sodium Chloride / Q000008:administration & dosage; D013997:Time Factors; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D012965:Sodium Chloride; D000093542:Gemcitabine
keywords: Gemcitabine; Infusion devices; Occupational exposure; Pharmacokinetics; Rinsing step