Your browser doesn't support javascript.
loading
Semimechanistic Modeling of the Effects of Blast Overpressure Exposure on Cefazolin Pharmacokinetics in Mice.
Selig, Daniel J; Chin, Geoffrey C; Bobrov, Alexander G; DeLuca, Jesse P; Getnet, Derese; Livezey, Jeffrey R; Long, Joseph B; Sajja, Venkatasivasai S; Swierczewski, Brett E; Tyner, Stuart D; Antonic, Vlado.
Afiliação
  • Selig DJ; Walter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.) daniel.j.selig.mil@mail.mil.
  • Chin GC; Walter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.).
  • Bobrov AG; Walter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.).
  • DeLuca JP; Walter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.).
  • Getnet D; Walter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.).
  • Livezey JR; Walter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.).
  • Long JB; Walter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.).
  • Sajja VS; Walter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.).
  • Swierczewski BE; Walter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.).
  • Tyner SD; Walter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.).
  • Antonic V; Walter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.).
J Pharmacol Exp Ther ; 379(2): 175-181, 2021 11.
Article em En | MEDLINE | ID: mdl-34433578
Cefazolin is a first-line antibiotic to treat infection related to deployment-associated blast injuries. Prior literature demonstrated a 331% increase cefazolin liver area under the curve (AUC) in mice exposed to a survivable blast compared with controls. We repeated the experiment, validated the findings, and established a semimechanistic two-compartment pharmacokinetic (PK) model with effect compartments representing the liver and skin. We found that blast statistically significantly increased the pseudo-partition coefficient to the liver by 326% (95% confidence interval: 76-737%), which corresponds to the observed 331% increase in cefazolin liver AUC described previously. To a lesser extent, plasma AUC in blasted mice increased 14-45% compared with controls. Nevertheless, the effects of blast on cefazolin PK were transient, normalizing by 10 hours after the dose. It is unclear as to how this blast effect t emporally translates to humans; however, given the short-lived effect on PK, there is insufficient evidence to recommend cefazolin dosing changes based on blast overpressure injury alone. Clinicians should be aware that cefazolin may cause drug-induced liver injury with a single dose and the risk may be higher in patients with blast overpressure injury based on our findings. SIGNIFICANCE STATEMENT: Blast exposure significantly, but transiently, alters cefazolin pharmacokinetics in mice. The questions of whether other medications or potential long-term consequences in humans need further exploration.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Traumatismos por Explosões / Cefazolina / Doença Hepática Induzida por Substâncias e Drogas / Antibacterianos / Modelos Biológicos Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Traumatismos por Explosões / Cefazolina / Doença Hepática Induzida por Substâncias e Drogas / Antibacterianos / Modelos Biológicos Idioma: En Ano de publicação: 2021 Tipo de documento: Article