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

Objective: Zeneo¹ is 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.

Research design and methods: 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.

Main outcome measures: The primary pharmacokinetic outcome parameters were AUC_(0–t) and C_max. Bioequivalence was assessed by standard criteria: whether 90% confidence intervals of geometric mean ratios for the two administration methods were within 80–125%.

Results: 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 C_max were fulfilled for abdominal administration but not for the overall analysis. Injection via the needle-free injection device was well tolerated.

Limitations: Limitations include conducting the study in healthy volunteers and the relatively small subject number (albeit satisfactory for bioequivalence).

Conclusions: 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.