G. Dubrovsky1, N. Huynh1, J. Rouch1, J. P. Koulakis2, D. P. Nicolau3, C. A. Sutherland3, S. Putterman2, J. Dunn1 2University Of California – Los Angeles,Department Of Physics And Astronomy,Los Angeles, CA, USA 3Hartford Hospital,Center For Anti-Infective Research & Development,Hartford, CT, USA 1University Of California – Los Angeles,Division Of Pediatric Surgery, Department Of Surgery, David Geffen School Of Medicine,Los Angeles, CA, USA
Introduction:
In the US, FDA-approved administration routes for cefazolin include intravenous and intramuscular. Subcutaneous administration of antibiotics is not well described in the literature, but has been used in other countries and appears to be a convenient method of drug delivery in certain cases. During surgery, we hypothesize that subcutaneous injection may provide higher local concentrations of antibiotic at the incision site and thus will lower the rate of surgical site infections (SSIs). To better understand the kinetics following subcutaneous injection, we describe the serum concentration levels of cefazolin in a porcine model as an estimate of the subcutaneous concentrations.
Methods:
Inhaled gas anesthesia was administered to Yucatan pigs. A femoral arterial catheter was placed. The pigs were administered 20mL of 25 mg/kg cefazolin subcutaneously, and serial blood samples were taken for 2 hours. Blood samples were analyzed for cefazolin concentration using chromatography. The elimination rate constant was calculated by linear regression to the semi-log plot of the terminal phase of the serum concentrations. Area under the curve was calculated using the linear trapezoidal rule until the final measured concentration. The final concentration divided by the elimination rate constant was added to this.
Results:
Maximum serum concentrations of cefazolin are achieved 44.3 minutes after the time of subcutaneous injection, and are 23.7 µg/mL (Figure 1). The elimination rate constant is .004 minutes -1 and the half-life is 173 minutes. The area under the curve is 4600 µg*min/mL and the clearance is 5.4 mL/(kg*min). The relative bioavailability of subcutaneous injection is 88%.
Conclusion:
We describe the pharmacokinetics of subcutaneous administration of cefazolin. This route shows good bioavailability, although the maximum serum concentrations achieved with subcutaneous injection are not as high as those from IV injection. The serum levels have a lower peak, but the medication remains in the blood for a longer period of time. As a result, higher doses of antibiotic can be injected locally without incurring systemic toxicity. Subcutaneous administration will therefore result in higher concentrations of antibiotic at the incision site than standard IV administration and thus may be more effective in preventing SSIs. Further studies are needed to detail the exact effect of subcutaneous antibiotic injection on SSI rates.