A new, patient-friendly, needleless methotrexate administration method using the pyro-drive jet injector in rats

Methotrexate (MTX) is the anchor first-line drug for the treatment of rheumatoid arthritis (RA) in the RA guidelines of the ACR, JCR and EULAR. In the guidelines, MTX is primarily administered orally as low-dose pulse therapy. However, oral MTX therapy has a large interindividual variation of drug efficacy/adverse drug reactions due to bioavailability (BA) differences and it is often associated with gastrointestinal disturbances, making some patients unable to continue oral MTX therapy. MTX subcutaneous (SC) administration involves pain at the injection site and there are regulatory issues in disposal related to medical waste. The pyro-drive jet injector (PJI) is an innovative, needle-free drug delivery system that enables targeted delivery of drugs. This study investigated the pharmacokinetics (PK) and BA of MTX via the PJI in rats. PJI-injected India ink indicated penetration into the subcutis. The AUC_0-∞ after oral (PO) administration was significantly less than that after intravenous (IV), SC, and PJI administration. Absolute BA values with PO, SC, and PJI administration were 30.6%, 99.1%, and 100.8%, respectively. The relative BA of the PJI compared with the SC group was 101.7%. The administration of MTX using the PJI may be useful in clinical practice, but further studies, such as BA or bioequivalence tests, are necessary in animal species with skin similar to human skin or in humans.