RESUMEN
We present data on pharmacokinetics of free and liposomal forms of gentamicin. Comparative study of two drug forms showed that immobilization of gentamicin in liposomes significantly increased most important pharmacokinetic parameters of the antibiotic (AUC, Cmax, MRTpo, T(1/2), Kel, Vzpo) and reduced Clpo and Kel.
Asunto(s)
Antibacterianos/farmacocinética , Gentamicinas/farmacocinética , Liposomas/metabolismo , Animales , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Gentamicinas/administración & dosificación , Gentamicinas/farmacología , Inyecciones Intraperitoneales , Radioisótopos de Yodo/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Liposomas/ultraestructura , Ratones , Microscopía Electrónica , Espectrofotometría , Factores de TiempoRESUMEN
Glanders is a zoonotic infection inducing acute forms of the disease (pneumonia, sepsis) in humans and animals under certain conditions, which even with the use of modern chemotherapy have unfavourable prognosis. Insufficient of efficacy of antibiotics with in vitro low MIC for planktonic bacterial suspension of Burkholderia mallei in chemotherapy of acute forms of glanders was due to the capacity of the pathogen for intracellular survival and formation of biofilms. Under such conditions the susceptibility of B. mallei to antibiotics lowered by several orders of magnitude. Chemotherapy of the glanders acute forms in animals usually provided only an increase of the lifespan, while among the survivors there was recorded a high relapse rate. More favourable outcomes were observed with the use of in vitro effective antibiotics in the form of clathrate compounds or especially liposomal forms. In the experiments with golden hamsters the survival rate reached 100% in 1000 Dlm infection even with the treatment onset by meropenem liposomal form 48 hours after the infection. Chemotherapeutics in the liposomal form significantly lowered resistance of B. mallei in both the experiments with a suspension of planktonic organisms and the use of bacteria interned in eukaryotic cells (Tetrahymena pyriformis).
Asunto(s)
Antibacterianos/farmacología , Burkholderia mallei/efectos de los fármacos , Muermo/tratamiento farmacológico , Tienamicinas/farmacología , Enfermedad Aguda , Animales , Burkholderia mallei/patogenicidad , Ceftazidima/farmacología , Cricetinae , Doxiciclina/farmacología , Femenino , Fiebre/tratamiento farmacológico , Muermo/etiología , Muermo/microbiología , Muermo/mortalidad , Liposomas , Masculino , Meropenem , Mesocricetus , Pruebas de Sensibilidad Microbiana , Tasa de Supervivencia , Terpenos/química , Terpenos/farmacologíaRESUMEN
A new method for obtaining the liposomal formulation of streptomycin and tetracycline is described in the present work. The physicochemical properties of this formulation were evaluated. We compared the effects of free and liposomal formulations from streptomycin and tetracycline on activity of liver enzymes in albino mice. Immobilization of antibiotics in liposomes was followed by a decrease in the inhibitory effect on protease, alkaline phosphatase, and phosphorylase. The influence of this preparation on ATPase was reduced by 2 times.
Asunto(s)
Fosfatasa Alcalina/metabolismo , Liposomas/metabolismo , Hígado/enzimología , Fosforilasas/metabolismo , Inhibidores de Proteasas/metabolismo , Estreptomicina/farmacología , Tetraciclina/farmacología , Fosfatasa Alcalina/antagonistas & inhibidores , Animales , Hígado/efectos de los fármacos , Ratones , Fosforilasas/antagonistas & inhibidoresRESUMEN
Preparation and physicochemical properties of liposome-incorporated tetracycline are described. Comparison of the effects of tetracycline hydrochloride in free and liposome-incorporated forms on enzymatic functions of the liver showed that immobilization of the antibiotic into liposomes protects liver cells from functional disturbances.
Asunto(s)
Hígado/efectos de los fármacos , Hígado/enzimología , Tetraciclina/farmacología , Adenosina Trifosfatasas/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Animales no Consanguíneos , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Liposomas , Extractos Hepáticos/metabolismo , Pruebas de Función Hepática , Ratones , Fosforilasas/metabolismo , Tetraciclina/administración & dosificación , Factores de TiempoRESUMEN
The data on preparation of liposome-entrapped gentamicin sulfate and cefoperazone and their investigation on albino mice with staphylococcal destructive pneumonia are presented. Comparative study of the efficacy of gentamicin sulfate and cefoperazone in free and liposome-entrapped forms showed that immobilization of the antibiotics in phospholipid vesicles provided a 2-fold increase of their efficacy.