Evaluation of Blast Overpressure Exposure Effects on Concentration of Antibiotics in Mice

Autor:	Brittany I Garry, Joseph B. Long, Brittney Potter, Jason C. Sousa, Jonathan P. Shearer, Venkatasivasaisujith Sajja, Vlado Antonic, Ken Nguyen, Chad C. Black, Maria Medina-Rojas, Yonas Alamneh, Samandra T. Demons, Chau Vuong, Daniel V. Zurawski, Donna M. Wilder, Stuart D. Tyner
Rok vydání:	2020
Předmět:	medicine.drug_class Antibiotics Cefazolin Explosions Context (language use) Pharmacology Mice Pharmacokinetics Blast Injuries In vivo Pressure medicine Animals Mice Inbred BALB C business.industry Basic Local Alignment Search Tool Public Health Environmental and Occupational Health General Medicine IV injection Anti-Bacterial Agents Disease Models Animal ROC Curve Area Under Curve Pharmacodynamics business medicine.drug
Zdroj:	Military Medicine. 185:256-262
ISSN:	1930-613X 0026-4075
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1cb0a1d34c676aedc11103c44e423bf6 https://doi.org/10.1093/milmed/usz212 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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