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Objective Infection as sequelae to explosion-related injury is an enduring threat to our troops. There are limited data on the effects of blast on antibiotic pharmacokinetics (PK), pharmacodynamics (PD), and efficacy. The observational study presented here is our Institute’s first attempt to address this issue by combining our existing interdepartmental blast, infection modeling, and in vivo PK/PD capabilities and was designed to determine the PK effects of blast on the first-line antibiotic, cefazolin, in an in vivo mouse model. Methods A total of 160 male BALB/c mice were divided to sham and blast (exposed to blast overpressure of 19 psi) in two biological replicates. At 1 hour after blast/sham exposure, the animals received IV injection of cefazolin (328 mg/kg). Animals were euthanized at 3 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, or 10 hours after the injection. Plasma and liver were analyzed for concentration of cefazolin using mass-spectrometry. Results We observed increases in the concentration of cefazolin in the plasma and liver of blast exposed animals at later time points and increase in elimination half-life. Conclusion Our results indicate that blast-induced physiologic changes significantly influence cefazolin PK and suggest that efficacy could be affected in the context of the blast; assessment of efficacy and PD effects require further investigation. Metabolic changes resulting from blast may influence other classes of antibiotics and other therapeutics used with these injuries. Therefore, this may have important treatment considerations in other areas of military medicine.

Particle size is an important determinant of gastrointestinal absorption of compounds administrated orally. The present study evaluates the effect of a reduction in particle size assessed by homogenization, sonication, and homogenization plus sonication on the bioavailability of imidazolidinedione (IZ), an antimalarial compound with known causal prophylactic activity and radical cure of relapsing malaria. Formulations were administrated intragastrically to mice, and blood samples were collected for LC-MS/MS analysis. The homogenization method manually decreased particle size with minimal variance, resulting in a mean particle diameter of 42.22 μm, whereas the probe sonication method evenly distributed pulses of sound to break apart particles, resulting in a mean diameter of 1.50 μm. Homogenization plus sonication resulted in a mean particle diameter of 1.44 μm, which was similar to that of the sonication method alone. The compound suspensions did not show a significant difference in mean particle size between the different vehicles. The sonically engineered microparticle delivers high sonic energy to the suspension leads to faster breakdown and stabilizing of the micronized particles when compared with homogenizer. The bioavailability of the small particle IZ formulation was 100%, compared to the 55.79% relative bioavailability of IZ with larger particle size. These initial data clearly show that a reduction in particle size of orally administered IZ with probe sonication could significantly increase bioavailability in rodent animals that is affected by a high first-pass effect.