Pharmacokinetic Response after Subcutaneous Administration of Ceftriaxone.

Background:

Ceftriaxone is a widely prescribed injectable cephalosporin antibiotic and is the most commonly used agent in outpatient parental antimicrobial therapy (OPAT), due to its safety profile and once a day dosing. Subcutaneous (SC) administration of ceftriaxone may offer a more convenient, safer and lower cost alternative to IV administration by avoiding the need for vascular access and use of Peripherally Inserted Central Catheters (PICC line). These results represent a pharmacokinetic comparison of SC administration of ceftriaxone with IV administration.

Methods:

This was a randomized, three-way partially blinded crossover study in healthy adult subjects.   SC dosing consisted of 1 g (100 mg/mL/10 mL) and 2 g (200mg/mL/10 mL) administered with a syringe pump over 2 hours.  The 1 g IV dose was administered per the label over 30 minutes.   

 

Results:

A total of 18 subjects were enrolled in and completed the study. Subcutaneous administration resulted in complete bioavailability.  The geometric mean absolute bioavailability following subcutaneous administration was 107%.   

Antimicrobial coverage was equivalent to IV administration.   The proportion of time-ceftriaxone concentrations above the reference MIC (4 µg/mL) was 111% for the 1 g SC administration compared to the IV infusion.  The study met the pre-defined end-points for non-inferiority of antimicrobial coverage.

Plasma concentrations of ceftriaxone following SC administration of 2 grams were approximately 60% over levels observed after 1 gram.

Figure 1: Mean Plasma Ceftriaxone Concentration-Time Data Overlaid by Treatment

                       

Conclusion:

The SC administration of 1 gram ceftriaxone over 2 hours results in complete bioavailability (107%) and equivalent antimicrobial coverage when compared to IV. The study met predefined non-inferiority criteria for antimicrobial coverage (time over MIC).   

SC administration of ceftriaxone offers a novel delivery mode for treatment of susceptible infections without the need for vascular access. 

In the future, SC administration via a wearable patch pump may eliminate the need for long-term IV catheters and provide a safer, more convenient and lower cost alternative to traditional OPAT therapy.  

ClinicalTrials.gov Identifier: NCT02561442