title: Single-center, single-dose, open-label, randomized, two-period crossover study on the bioavailability of methotrexate administered using a novel prefilled, needle-free delivery system.
abstract: Zeneo1is a needle-free injection device. We performed a pharmacokinetic study to investigate the bioequivalence of methotrexate administered subcutaneously using either the needle-free injection device or a conventional needle and syringe.
  
  
  
  This was a single-dose, open-label, laboratory-blind, randomized crossover study performed in adult healthy volunteers. Each participant received two methotrexate injections (each 25 mg), one via needle-free injection device and one via conventional injection, with a 21-28 day wash-out interval between dosing. For each participant, the administration site for both injections was either the abdomen or the thigh.
  
  
  
  The primary pharmacokinetic outcome parameters were AUC(0-t)and Cmax. Bioequivalence was assessed by standard criteria: whether 90% confidence intervals of geometric mean ratios for the two administration methods were within 80-125%.
  
  
  
  Fifty-two individuals completed the study. Bioequivalence criteria were met for AUC(0-t), for the overall analysis (both injection sites: 90% confidence interval: 99.4-103.1%), and for each injection site separately. Bioequivalence was similarly demonstrated with AUC(0-∞). Bioequivalence criteria for Cmaxwere fulfilled for abdominal administration but not for the overall analysis. Injection via the needle-free injection device was well tolerated.
  
  
  
  Limitations include conducting the study in healthy volunteers and the relatively small subject number (albeit satisfactory for bioequivalence).
  
  
  
  This study shows that methotrexate injection via needle-free injection device is bioequivalent to a conventional needle and syringe in relation to AUC(0-t)and AUC(0-∞). Studies of needle-free injection device use in patients requiring methotrexate therapy are planned.
authors.affiliation: a Department of Internal Medicine , Université de Caen , Caen , France.
authors.forename: Boris
authors.initials: B
authors.lastname: Bienvenu
authors.affiliation: a Department of Internal Medicine , Université de Caen , Caen , France.
authors.forename: Achille
authors.initials: A
authors.lastname: Aouba
authors.affiliation: b Centre National de Référence pour les Maladies Auto-Immunes Systémiques Rares, Hôpitaux Universitaires de Strasbourg , Strasbourg , France.
authors.forename: Jacques-Eric
authors.initials: JE
authors.lastname: Gottenberg
authors.affiliation: c Bicêtre University Hospital , Le Kremlin Bicêtre , France.
authors.forename: Celine
authors.initials: C
authors.lastname: Verstuyft
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D008875:Middle Aged; D009339:Needles
chemical_list: D008727:Methotrexate
keywords: Autoinjector; bioequivalence; methotrexate; pharmacokinetics