RESUMEN
Perflubron (perfluoroocytlbromide, PFOB) emulsion concentrations of 100%, 90%, or 60% w/v were administered to mice with and without 3 types of murine malignant tumor implants, and the distribution in blood, tumor, lung, liver and spleen were studied 48 hours after a dose of 10 or 3 g/Kg of PFOB. The most important changes were seen in the blood where the PFOB concentration [PFOB] was decreased in tumor bearing mice (TBM). Blood [PFOB] was also decreased in TBM and normal mice (NM) that received the 60% emulsion. Liver [PFOB] was increased in TBM. Lung [PFOB] was directly proportional to the emulsion concentration with the 10g/Kg dose. No major differences were seen in the biodistribution between the 100% and 90% emulsions using 10g/Kg, in spite of differences in composition and manufacturing history.
Asunto(s)
Sustitutos Sanguíneos/farmacocinética , Medios de Contraste/farmacocinética , Fluorocarburos/farmacocinética , Neoplasias Experimentales/metabolismo , Animales , Sustitutos Sanguíneos/administración & dosificación , Medios de Contraste/administración & dosificación , Emulsiones , Fluorocarburos/administración & dosificación , Hidrocarburos Bromados , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Neoplasias Experimentales/terapia , Distribución TisularRESUMEN
The biodistribution of Perflubron (perfluorocytylbromide, PFOB) was studied by infusing 10 or 3 g/Kg doses of 90% and 100% w/v emulsions into Balb C mice with and without malignant mammary tumor implants. PFOB concentrations were measured in blood, liver, spleen, lung and tumor, and X-rays were taken 48 hours after infusion. Ibuprofen (IBU) was given intraperitoneally 10 mg/Kg dialy for 3 days to study the effects of cyclooxygenase blockade. The results showed that the blood [PFOB] in tumor-bearing mice (TBM) was only 3.6% of that measured in normal mice (NM), and the liver [PFOB] was increased by 59%. The lung [PFOB] increase with IBU therapy in NM was highly significant. IBU therapy resulted in a 98% and 468% increase in blood [PFOB] in normal and TBM, respectively. Smaller but statistically significant changes occurred in blood [PFOB] with saline and sham injections. Tumor [PFOB] was lower by 17% (P = .028) in mice treated with IBU. Smaller decreases were seen with saline and sham injections but did not achieve statistical significance. In conclusion, the presence of this malignant tumor resulted in changes that might influence the usefulness of PFOB as a contrast agent and as an adjuvant for radiation and chemotherapy. This study shows that cyclooxygenase inhibition significantly modified the pharmacodynamics of PFOB emulsions in blood, tumor and lung. The changes seen in the saline placebo and sham category were attributed to stress from procedures.
Asunto(s)
Fluorocarburos/farmacocinética , Ibuprofeno/farmacología , Neoplasias Mamarias Experimentales/metabolismo , Animales , Medios de Contraste/administración & dosificación , Medios de Contraste/farmacocinética , Emulsiones , Fluorocarburos/administración & dosificación , Hidrocarburos Bromados , Tasa de Depuración Metabólica/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Fármacos Sensibilizantes a Radiaciones/farmacocinética , Distribución Tisular/efectos de los fármacosRESUMEN
Uptake of iopanoic acid (IOP) and iopanoate glucuronide (IOP-G) was studied in 3-day primary cultures of rat hepatocytes isolated by the collagenase perfusion method. 125I activity of cells after incubation with 125I-IOP (10-100 microM) and 125I-IOP-G (10-100 microM) was used as a measure of uptake. At each concentration, uptake was linear for the first 45 sec. In the absence of albumin, the initial uptake velocity was directly proportional to the concentration or IOP or IOP-G and was nonsaturable up to 100 microM. The calculated uptake rate constants for IOP and for IOP-G were 0.059 and 0.048 nmole/(mg protein X min X microM), respectively. IOP uptake was not inhibited by sodium taurocholate nor by the contrast agents iodipamide, ipodate, and iopronic acid. The data indicate that the enhancement of IOP excretion by bile salts noted in vivo does not occur at the uptake step and that the hepatic uptake of both IOP and IOP-G in the absence of albumin is limited by diffusion.
Asunto(s)
Ácido Yopanoico/análogos & derivados , Ácido Yopanoico/metabolismo , Hígado/metabolismo , Adsorción , Animales , Células Cultivadas , Hígado/efectos de los fármacos , Ratas , Ácido Taurocólico/farmacologíaRESUMEN
Uptake of iopanoic acid (IOP) was studied in 3-day primary cultures of rat hepatocytes isolated by the collagenase perfusion method. 125I activity of cells after incubation with 125I-IOP (1.0-100 microM) was used as a measure of uptake. At each IOP concentration uptake was linear for the first 45 s. The initial uptake velocity was directly proportional to IOP concentration and was nonsaturable up to 100 microM. The calculated uptake rate constant was 0.67 nmol . mg prot-1 . min-1 . microM-1. Uptake was only slightly reduced when the incubation was performed at 4 degrees C and was independent of sodium concentration. Albumin in the medium reduced IOP uptake. Uptake, however, was always greater than that predicted from the unbound IOP concentration alone. The data indicate that the hepatocyte uptake of IOP occurs by both a passive process and a saturable process. The saturable uptake component depends on an albumin-IOP-hepatocyte interaction. The influence of albumin on uptake occurs possibly by an undefined specific cell surface phenomenon of albumin that promotes uptake of IOP or by enhancement of the diffusibility of IOP across the unstirred layer.
Asunto(s)
Ácido Yopanoico/metabolismo , Hígado/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Células Cultivadas , Radioisótopos de Yodo , Cinética , Ratas , Albúmina Sérica/farmacologíaRESUMEN
Because of relatively low acute toxicity, iosulamide meglumine has been recommended as an improved contrast material for intravenous cholangiography. It has been postulated that high doses of the compound could be given safely with the expectation of achieving greater biliary excretion and improved opacification of the biliary tree. Experiments performed in dogs show that higher rates of infusion of iosulamide result in greater urinary elimination without additional biliary excretion. Consequently, iosulamide is unlikely to have any special advantage as a contrast agent.