RESUMEN
The purpose of this study was to examine the allometric analysis of ciprofloxacin and enrofloxacin using pharmacokinetic data from the literature. The pharmacokinetic parameters used were half-life, clearance and volume of distribution. Relationships between body weight and the pharmacokinetic parameter were based on the empirical formula Y = aW(b), where Y is half-life, clearance or volume of distribution, W the body weight and a is an allometric coefficient (intercept) that is constant for a given drug. The exponential term b is a proportionality constant that describes the relationship between the pharmacokinetic parameter of interest and body weight. A total of 21 different species of animals were studied. Results of the allometric analyses indicated similarity between clearance and volume of distribution as they related to body weight for both drugs. Results of the current analyses indicate it is possible to use allometry to predict pharmacokinetic variables of enrofloxacin or ciprofloxacin based on body size of species. This could provide information on appropriate doses of ciprofloxacin and enrofloxacin for all species.
Asunto(s)
Antiinfecciosos/farmacocinética , Ciprofloxacina/farmacocinética , Fluoroquinolonas/farmacocinética , Quinolonas/farmacocinética , Animales , Enrofloxacina , Humanos , Modelos Biológicos , Especificidad de la Especie , Drogas Veterinarias/farmacocinéticaRESUMEN
Plasma, urine, and skin drug concentrations were determined for dogs (n=12) given five daily oral doses of marbofloxacin (MAR) (2.75 mg/kg), enrofloxacin (ENR) (5.0 mg/kg) or difloxacin (DIF) (5.0 mg/kg). Concentrations of the active metabolite of ENR, ciprofloxacin (CIP), were also determined. The three-period, three-treatment crossover experimental design included a 21-day washout period between treatments. Area under the plasma drug concentration vs. time curve (AUC0-last, microg/mLxh of MAR was greater than for ENR, CIP, ENR/CIP combined, and DIF. Maximum concentration (Cmax) of MAR was greater than ENR, CIP, and DIF. Time of maximum plasma concentration (Tmax) was similar for MAR and DIF; Tmax occurred earlier for ENR and later for CIP. Plasma half-life (t1/2) of MAR was longer than for ENR, CIP, and DIF. Urine concentrations of DIF were less than MAR or ENR/CIP combined, but urine concentrations of MAR and ENR/CIP combined did not differ. DIF skin concentrations were less than the concentrations of MAR or ENR/CIP combined 2 h after dosing, but skin concentrations of MAR and ENR/CIP combined did not differ.
Asunto(s)
Antiinfecciosos/farmacocinética , Ciprofloxacina/análogos & derivados , Perros/metabolismo , Fluoroquinolonas , Administración Oral , Animales , Antiinfecciosos/administración & dosificación , Antiinfecciosos/sangre , Antiinfecciosos/orina , Área Bajo la Curva , Ciprofloxacina/metabolismo , Ciprofloxacina/farmacocinética , Estudios Cruzados , Enrofloxacina , Femenino , Quinolonas/farmacocinética , Piel/metabolismoRESUMEN
The effect of yohimbine pretreatment on gastric emptying of a liquid marker in horses was evaluated by measuring serum concentrations of acetaminophen. Gastric emptying was determined in normal, fasted horses, in horses given endotoxin (E. coli 055 B5; 0.2 microg/kg) intravenously, and in horses given yohimbine (0.25 mg/kg, IV, over 30 minutes) plus endotoxin. Acetaminophen (20 mg/kg) was given by stomach tube 15 minutes after the endotoxin infusion. Blood samples for acetaminophen analysis were collected, and time to reach the peak serum concentration (Tmax), the maximum serum concentration (Cmax) and the area under the acetaminophen serum concentration versus time curve (AUC) were determined for each treatment group. Endotoxin significantly increased Tmax, indicating a profound delay in gastric emptying and yohimbine pretreatment significantly (P < or = 0.05) prevented this effect.
Asunto(s)
Antagonistas Adrenérgicos alfa/farmacología , Endotoxinas/farmacología , Vaciamiento Gástrico/efectos de los fármacos , Caballos/fisiología , Yohimbina/farmacología , Acetaminofén/farmacocinética , Antagonistas Adrenérgicos alfa/farmacocinética , Animales , Antiinflamatorios no Esteroideos/farmacocinética , Área Bajo la Curva , Interacciones Farmacológicas , Femenino , Yohimbina/farmacocinéticaAsunto(s)
Bienestar del Animal , Caballos , Resistencia Física , Deportes , Bienestar del Animal/legislación & jurisprudencia , Animales , Doping en los Deportes , Enfermedades de los Caballos/etiología , Enfermedades de los Caballos/prevención & control , Deportes/legislación & jurisprudencia , Estados UnidosRESUMEN
OBJECTIVE: The effect of sedation on gastric emptying was evaluated in six ponies by monitoring serum concentrations of acetaminophen (AP) after intragastric administration. EXPERIMENTAL DESIGN: Prospective randomized experimental study. ANIMALS: Six adult ponies, 135 to 275 kg. METHODS: Fifteen minutes after the intravenous administration of xylazine (1 mg/kg), butorphanol (0.05 mg/kg), acepromazine (0.05 mg/kg) or saline, ponies were given AP (20 mg/kg in 350 mL water) by stomach tube. Blood for AP analysis was collected at baseline and 15, 30, 45, 75, 90, 105, and 120 minutes after AP administration. The time (Tmax) to reach peak serum concentration (Cmax), and the area under the AP serum concentration versus time curve (AUC) were determined for each treatment group. RESULTS: Tmax was 31 mins in the control group, and this increased significantly (P<.05) after sedation. Cmax decreased (P<.05) after xylazine administration, and AUC decreased (P<.05) after acepromazine. CONCLUSIONS: This study indicated that sedation has a significant effect on the gastric emptying rate of a liquid in ponies.
Asunto(s)
Acetaminofén/farmacocinética , Analgésicos no Narcóticos/farmacocinética , Vaciamiento Gástrico/efectos de los fármacos , Caballos/metabolismo , Hipnóticos y Sedantes/farmacología , Acepromazina/farmacología , Acetaminofén/administración & dosificación , Acetaminofén/sangre , Agonistas alfa-Adrenérgicos/farmacología , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/sangre , Analgésicos Opioides/farmacología , Animales , Antipsicóticos/farmacología , Área Bajo la Curva , Butorfanol/farmacología , Femenino , Intubación Gastrointestinal/veterinaria , Estudios Prospectivos , Xilazina/farmacologíaRESUMEN
The effect of metoclopramide on gastric emptying of a liquid marker in horses was evaluated by measuring serum concentrations of acetaminophen. Gastric emptying was determined in normal, fasted horses (n = 7), horses given endotoxin intravenously (n = 7), and horses given intravenous metoclopramide plus endotoxin (n = 6). The mean time to reach maximum serum acetaminophen concentration (Tmax), the maximum serum concentration (Cmax), and the area under the serum acetaminophen concentration vs time curve (AUC) were compared among treatment groups. Endotoxin caused a profound delay in gastric emptying, and pretreatment with metoclopramide significantly (P < 0.05) ameliorated this effect.
Asunto(s)
Antagonistas de Dopamina/farmacología , Endotoxinas/farmacología , Vaciamiento Gástrico/efectos de los fármacos , Caballos/fisiología , Metoclopramida/farmacología , Acetaminofén/sangre , Acetaminofén/farmacocinética , Animales , Antiinflamatorios no Esteroideos/sangre , Área Bajo la Curva , Biomarcadores , FemeninoRESUMEN
The dose of most cancer chemotherapeutic drugs administered to dogs is calculated on the basis of estimated body surface area (BSA); however results of some chemotherapy trials have revealed that this dosing method increases toxicosis in small dogs. The current formula used to estimate BSA in dogs may be inaccurate or the assumption that BSA correlates with chemotherapeutic drug exposure may be unfounded. Results presented in this review suggest that canine BSA estimates may be inaccurate because the values for the constant (K) and exponent (a) in the formulae (BSA = K.Wa) are incorrect or because a linear parameter such as body length is lacking from the formulae. Results that suggest the relationship between BSA and the physiologic/pharmacologic factors that influence drug exposure may not be closely correlated are also presented. Studies are warranted to determine whether there are dosing methods that normalize chemotherapeutic drug toxicity in dogs.
Asunto(s)
Superficie Corporal/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Esquema de Medicación/veterinaria , Animales , PerrosRESUMEN
Anticancer drug dosages that specify the maximum dose and minimum dosing interval that are tolerated in a population of dogs are commonly recommended. Because the differences between the effective and toxic doses of most cancer chemotherapeutics is slight, it is important to achieve therapeutic concentrations in tumor tissues at the same time that concentrations in nontarget tissues are minimized. In order to determine the dosage regimen that will most likely accomplish these goals, similar drug concentrations must be achieved in all patients dosed according to a specific regimen. Dosing based on body surface area (BSA) is generally used in an effort to normalize drug concentrations. This is because it is well recognized that measures of many physiologic parameters that are responsible for drug disposition, including renal function and energy expenditure, can be normalized by use of BSA. However, there is substantial evidence that drug disposition is not always proportional to BSA. Differences in distribution, metabolism, and excretion pathways may preclude dose extrapolation among species or among individuals within a species based on BSA. Moreover, genetic differences in drug metabolism are well recognized in humans and in laboratory animals, and it is likely that similar differences exist among breeds of dogs. A review of the pharmacokinetic disposition of several cancer chemotherapeutics suggests that studies are needed to determine the most effective method to achieve equivalent anticancer drug concentrations in diverse veterinary patients.
Asunto(s)
Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Superficie Corporal/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Esquema de Medicación/veterinaria , Animales , PerrosRESUMEN
This study investigated the effect of lidocaine i.v. on halothane minimum alveolar concentration (MAC) in ponies. Six ponies were anaesthetised with thiopentone and succinylcholine, intubated and anaesthesia maintained with halothane. Ventilation was controlled and blood pressure maintained within clinically acceptable limits. Following a 2 h equilibration period, baseline halothane MAC was determined. The ponies were then given a loading dose of lidocaine (2.5 or 5 mg/kg bwt) or saline over 5 min, followed by a constant infusion of lidocaine (50 or 100 microg/kg/min, or saline, respectively). The halothane MAC was redetermined after a 60 min infusion of lidocaine or saline. The baseline halothane MAC for the control group was mean +/- s.d. 0.94 +/- 0.03%, and no significant decrease occurred following saline infusion. Lidocaine decreased halothane MAC in a dose-dependent fashion (r = 0.86; P < 0.0003). The results indicate that i.v. lidocaine may have a role in equine anaesthesia.
Asunto(s)
Anestésicos por Inhalación/análisis , Anestésicos/farmacología , Halotano/análisis , Caballos/fisiología , Lidocaína/farmacología , Anestésicos/administración & dosificación , Anestésicos/sangre , Anestésicos por Inhalación/administración & dosificación , Animales , Estado de Conciencia/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Halotano/administración & dosificación , Infusiones Intravenosas/veterinaria , Lidocaína/administración & dosificación , Lidocaína/sangre , MasculinoRESUMEN
Gastric emptying was evaluated in ponies using the acetaminophen (AP) method. Fifteen minutes after i.v. administration of metoclopramide, erythromycin, yohimbine, atropine or saline, the ponies were given AP by stomach tube. Blood samples for AP analysis were collected at baseline and 15, 30, 45, 60, 75, 90, 105 and 120 min after AP administration. Time to reach peak serum concentration (Tmax), maximum serum concentration (Cmax) and area under the AP serum concentration vs. time curve (AUC) were determined for each treatment group. In the control group, Tmax was 31 min and this decreased significantly (P < 0.05) following the administration of metoclopramide. Atropine significantly increased Tmax and decreased Cmax and AUC. Yohimbine significantly increased AUC. Erythromycin did not significantly change any parameter. This study indicates that acetaminophen can be used to evaluate gastric emptying in ponies. The method is easy to perform and is minimally invasive. Metoclopramide stimulated gastric emptying of liquid in healthy, fasting ponies. Atropine significantly delayed, while erythromycin had little effect on, gastric emptying. Yohimbine increased the cumulative absorption of AP.
Asunto(s)
Acetaminofén , Analgésicos no Narcóticos , Vaciamiento Gástrico/fisiología , Caballos/fisiología , Acetaminofén/sangre , Acetaminofén/farmacocinética , Analgésicos no Narcóticos/sangre , Analgésicos no Narcóticos/farmacocinética , Animales , Antibacterianos/farmacología , Antieméticos/farmacología , Área Bajo la Curva , Atropina/farmacología , Eritromicina/farmacología , Vaciamiento Gástrico/efectos de los fármacos , Metoclopramida/farmacología , Parasimpatolíticos/farmacología , Simpaticolíticos/farmacología , Yohimbina/farmacologíaRESUMEN
The effect of cisapride pretreatment on gastric emptying in horses was determined by measuring serum concentrations of acetaminophen, a drug known to be readily absorbed in the small intestine but not in the stomach. The time to reach maximum serum acetaminophen concentrations (Tmax), the maximum serum concentrations (Cmax) and the area under the serum acetaminophen concentration vs. time curves (AUC) were compared among treatment groups. In the first part of the study, the effect of orally administered cisapride (0.1, 0.2 and 0.4 mg/kg bwt) on gastric emptying was examined in 6 normal fasted horses. In the second part of the study, gastric emptying in horses given endotoxin i.v. (n = 6) was compared to those that received cisapride per os prior to administration of endotoxin (n = 6) and those that received neither compound (n = 6). Cisapride did not alter gastric emptying in normal horses. Endotoxin caused a profound delay in gastric emptying and pretreatment with cisapride significantly attenuated this effect. It is concluded that cisapride may be useful as a prophylactic measure when administered prior to the development of endotoxaemia.
Asunto(s)
Endotoxinas/toxicidad , Vaciamiento Gástrico/efectos de los fármacos , Fármacos Gastrointestinales/farmacología , Enfermedades de los Caballos/tratamiento farmacológico , Obstrucción Intestinal/veterinaria , Piperidinas/farmacología , Acetaminofén/farmacocinética , Administración Oral , Analgésicos no Narcóticos/farmacocinética , Animales , Área Bajo la Curva , Cisaprida , Femenino , Fármacos Gastrointestinales/administración & dosificación , Fármacos Gastrointestinales/uso terapéutico , Enfermedades de los Caballos/inducido químicamente , Enfermedades de los Caballos/fisiopatología , Caballos , Obstrucción Intestinal/inducido químicamente , Obstrucción Intestinal/tratamiento farmacológico , Obstrucción Intestinal/fisiopatología , Piperidinas/administración & dosificación , Piperidinas/uso terapéutico , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/fisiopatología , Complicaciones Posoperatorias/veterinariaRESUMEN
The effect of phenylbutazone on gastric emptying in horses was determined by measuring serum concentrations of acetaminophen. Gastric emptying was determined in normal fasted horses (n = 6), horses given endotoxin intravenously (n = 6), horses given intravenous phenylbutazone (n = 6), and horses given intravenous phenylbutazone plus endotoxin (n = 6). The mean time to reach maximum serum acetaminophen concentration (Tmax), the maximum serum concentration (Cmax), and the area under the serum acetaminophen concentration versus time curve (AUC) were compared among treatment groups. Phenylbutazone did not alter gastric emptying in normal horses. Endotoxin caused a profound delay in gastric emptying, and pretreatment with phenylbutazone abolished this effect.
Asunto(s)
Acetaminofén/farmacocinética , Endotoxinas/toxicidad , Vaciamiento Gástrico/efectos de los fármacos , Fenilbutazona/farmacología , Animales , Endotoxinas/administración & dosificación , Escherichia coli , Ayuno , Femenino , Caballos , Inyecciones Intravenosas , Tasa de Depuración Metabólica , Fenilbutazona/administración & dosificaciónAsunto(s)
Anestesia , Anestésicos por Inhalación/metabolismo , Halotano/metabolismo , Caballos/metabolismo , Alveolos Pulmonares/metabolismo , Anestésicos por Inhalación/administración & dosificación , Anestésicos por Inhalación/farmacología , Animales , Estimulación Eléctrica , Extremidades , Halotano/administración & dosificación , Halotano/farmacología , Cabeza , Masculino , Movimiento/efectos de los fármacosRESUMEN
In the pharmacokinetic evaluation of a single doxorubicin dose calculated by body surface area (25 mg/m2) or body weight (1 mg/kg body weight) and given intravenously as a 10-, 15-, or 20-minute infusion, the rate of doxorubicin infusion (mg per minute per m2 or mg per minute per kg) correlated positively with clearance and the distribution rate constant alpha, and it inversely correlated with area under the plasma concentration versus time curve (AUC). These findings suggest that a slower infusion rate results in a greater AUC and longer distribution phase than a faster infusion rate and indicates the importance of normalizing dosage regimes by infusion rate rather than by infusion duration when considering dose-response phenomena in veterinary patients.
Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/farmacocinética , Enfermedades de los Gatos/metabolismo , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacocinética , Neoplasias de los Tejidos Blandos/veterinaria , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/veterinaria , Animales , Antibióticos Antineoplásicos/uso terapéutico , Área Bajo la Curva , Superficie Corporal , Peso Corporal/fisiología , Enfermedades de los Gatos/tratamiento farmacológico , Enfermedades de los Gatos/fisiopatología , Gatos , Relación Dosis-Respuesta a Droga , Doxorrubicina/uso terapéutico , Femenino , Fibrosarcoma/tratamiento farmacológico , Fibrosarcoma/metabolismo , Fibrosarcoma/veterinaria , Infusiones Intravenosas/veterinaria , Neoplasias Mamarias Animales/tratamiento farmacológico , Neoplasias Mamarias Animales/metabolismo , Neoplasias Mamarias Animales/fisiopatología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/veterinaria , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/metabolismo , Factores de TiempoRESUMEN
Six cycles of the maximum tolerable intravenous doses of lonidamine (400 mg/m2) and doxorubicin (30 mg/m2) were administered to three normothermic dogs and three dogs undergoing whole-body hyperthermia (WBH) (42 degrees C X 90 min), at 3-week intervals. Lonidamine pharmacokinetics was unaltered by WBH. WBH increased doxorubicin clearance 1.6-fold, however this trend was not statistically significant. WBH resulted in a 2.4-fold increase in the volume of distribution (Vdss) of doxorubicin relative to dogs treated under euthermic conditions (p < 0.001). This finding suggests tissue extraction of doxorubicin was increased by WBH. The specific tissues in which this occurred is unknown, but myelosuppression and cardiotoxicity were only minimally increased. Therefore, doxorubicin uptake in critical normal tissues was probably unaffected. The biochemical and haematologic toxicities observed 6 h and 1 week after each treatment did not appear to differ in character or severity from that reported in dogs receiving lonidamine +/- WBH or doxorubicin +/- WBH. These results suggest WBH did not decrease the maximum tolerable dose of doxorubicin when given with lonidamine, and that the antitumour activity of this combination should be assessed.
Asunto(s)
Antineoplásicos/farmacocinética , Doxorrubicina/farmacocinética , Doxorrubicina/toxicidad , Hipertermia Inducida , Indazoles/farmacocinética , Indazoles/toxicidad , Animales , Antineoplásicos/sangre , Antineoplásicos/toxicidad , Ácidos y Sales Biliares/sangre , Análisis Químico de la Sangre , Perros , Doxorrubicina/sangre , Indazoles/sangre , Hígado/efectos de los fármacos , Hígado/ultraestructura , Tasa de Depuración Metabólica , Microscopía Electrónica , Contracción Miocárdica/efectos de los fármacos , Miocardio/ultraestructura , Vacuolas/efectos de los fármacos , Vacuolas/ultraestructuraRESUMEN
Pharmacokinetics and toxicity of a single dose of doxorubicin, at dosages of 30 mg/m2 of body surface area and 1 mg/kg of body weight, were compared in 17 dogs. Effects of doxorubicin on complete blood cell count, platelet count, and the dogs' clinical condition were evaluated for 14 days. Cluster analysis, on the basis of clinical signs of doxorubicin toxicosis at the 30-mg/m2 dosage, revealed that 6 of 7 small dogs (< or = 10 kg) became ill, whereas 7 of 10 large dogs (> 10 kg) remained clinically normal. Small dogs that received doxorubicin at a dosage of 30 mg/m2 had higher peak plasma concentrations, greater area under the curve for plasma drug concentration vs time, longer drug elimination half-lives, greater volumes of distribution, and more clinical signs of toxicosis than had large dogs (P < or = 0.05). Five of 9 small dogs that received doxorubicin at a dosage of 30 mg/m2 developed severe myelosuppression (< 1 x 10(3) granulocytes/microliters). In contrast to the toxicoses with body surface area-based dosing, myelosuppression was not induced in small dogs that received doxorubicin at a dosage of 1 mg/kg. In small and large dogs given doxorubicin at a dosage of 1 mg/kg, pharmacokinetic characteristics and clinical signs of toxicosis were similar. Mean WBC counts and granulocyte counts for all dogs were lower on day 7 with 30 mg of doxorubicin/m2 (n = 17), compared with that for 1 mg of doxorubicin/kg (n = 14; P < or = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Perros/anatomía & histología , Doxorrubicina/farmacocinética , Doxorrubicina/toxicidad , Animales , Recuento de Células Sanguíneas/efectos de los fármacos , Superficie Corporal , Peso Corporal , Relación Dosis-Respuesta a Droga , Doxorrubicina/sangre , Femenino , Recuento de Leucocitos/efectos de los fármacos , Masculino , Neutrófilos/efectos de los fármacos , Recuento de Plaquetas/efectos de los fármacosRESUMEN
The United States pet population has been a vastly underutilized resource for cancer therapy studies. Naturally occurring tumors in dogs develop twice as frequently as in man, have histopathologic features and a biologic behavior similar to tumors in man, and progress at a more rapid rate than in man. Cancer is one of the leading causes of death in man and dogs. The canine malignancies that are of practical use for comparative therapeutic studies include lymphoma, mammary tumors, oral melanoma, lung tumors, nasal tumors, soft tissue sarcomas, and osteosarcoma. This report will discuss the comparative nature of these malignancies and the current trends in clinical cancer research, namely dose intensification and biomodulation, using naturally occurring tumors in client-owned dogs.
Asunto(s)
Enfermedades de los Perros , Neoplasias Experimentales , Neoplasias/veterinaria , Animales , Enfermedades de los Perros/epidemiología , Perros , Femenino , Humanos , Neoplasias/epidemiología , Neoplasias/patología , Neoplasias/terapia , Neoplasias Experimentales/patología , Neoplasias Experimentales/terapia , Investigación/tendencias , Estados Unidos/epidemiologíaRESUMEN
Effective antitumor photodynamic therapy (PDT) may be related to damage of vasculature within the tumor. The purpose of this study was to determine if tumor cells secrete factors that stimulate proliferation of human umbilical vein endothelial cells (HUVEC) and result in enhanced sensitivity of HUVEC to aluminum-sulfonated phthalocyanine (AlSPc)-PDT. Three human tumor cell lines--pharyngeal squamous carcinoma, colonic carcinoma, and mammary carcinoma--were used in this study. Co-culture of HUVEC and either squamous carcinoma or colonic carcinoma, but not mammary carcinoma, significantly increased HUVEC proliferation and AlSPc-PDT mediated cell damage. In addition, supernatant from squamous carcinoma and colonic carcinoma cultures also stimulated HUVEC proliferation and sensitivity to AlSPc-PDT. Both supernatant and cell lysate from squamous carcinoma cells contained angiogenic factors consistent with basic and acidic fibroblast growth factors, as evidenced by Western blot analysis and BALB/c 3T3 fibroblast cell proliferation assays. Collectively, these results suggest that selected tumor cell lines produce angiogenic factors that induce HUVEC proliferation and subsequently enhance sensitivity to AlSPc-PDT.
Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Carcinoma/metabolismo , Endotelio Vascular/efectos de los fármacos , Rayos Láser , Fotoquimioterapia , Células 3T3/efectos de los fármacos , Aluminio/farmacología , Animales , Western Blotting , Carcinoma/patología , Carcinoma de Células Escamosas/patología , División Celular/efectos de los fármacos , Línea Celular , Células Cultivadas , Endotelio Vascular/patología , Factor 1 de Crecimiento de Fibroblastos/metabolismo , Factor 1 de Crecimiento de Fibroblastos/farmacología , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Factor 2 de Crecimiento de Fibroblastos/farmacología , Humanos , Indoles/farmacología , Ratones , Ratones Endogámicos BALB C , Neovascularización Patológica , Compuestos Organometálicos/farmacología , Fármacos Sensibilizantes a Radiaciones/farmacología , Células Tumorales Cultivadas , Venas Umbilicales/citologíaRESUMEN
The effect of prior hyperthermia on the concentrations of adriamycin in tumors was examined. Chemically induced (9,10-dimethyl-1,2-benzanthracene) rat mammary adenocarcinomas were not heated or were heated one or two times (43.5 degrees C, 1 h; 24 h apart when two times) using an Nd:YAG laser. Rats were administered adriamycin (5 mg/kg, iv) 3 h after hyperthermia treatment. The concentrations of adriamycin in plasma and tissue were determined using high-performance liquid chromatography. Although plasma pharmacokinetics was unchanged by prior local hyperthermia, the concentration of adriamycin was significantly lower in tumors that had been heated previously compared to that in unheated tumors. Tumor blood flow rate was determined after an identical heating protocol using a reference sample technique with 113Sn microspheres. Tumor blood flow rate increased slightly during hyperthermia and then rapidly returned to control levels after hyperthermia. Decreased concentrations of adriamycin in tumors may result from biochemical changes induced by hyperthermia in neoplastic cells and may explain the adriamycin resistance in thermotolerant cells reported previously.
Asunto(s)
Doxorrubicina/farmacocinética , Hipertermia Inducida , Neoplasias Mamarias Experimentales/metabolismo , 9,10-Dimetil-1,2-benzantraceno , Animales , Terapia Combinada , Doxorrubicina/sangre , Doxorrubicina/uso terapéutico , Femenino , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Neoplasias Mamarias Experimentales/terapia , Ratas , Ratas Sprague-DawleyRESUMEN
The purpose of this study was to determine if recombinant angiogenic cytokines modulate the sensitivity of endothelial cells to the toxic effects of chloroaluminum sulphonated phthalocyanine (AlSPc) photodynamic therapy (PDT). Bovine pulmonary artery endothelial cells in 24-well tissue culture plates were pretreated for 24 hr with AlSPc and either acidic fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), tumor necrosis factor-alpha (TNF), interleukin-1-alpha (IL-1), or transforming growth factor-beta (TGF) followed by argon-pumped dye laser. Endothelial cell damage was monitored with 51chromium release. FGF, TGF, and, to a lesser extent, IL-1, enhanced the PDT-mediated damage to endothelial cells, whereas PDGF and TNF did not significantly modulate toxicity. The enhanced endothelial cell damage was seemingly not related to rate of cell proliferation or amount of photoactive drug uptake by the EC. These results suggest that presence of tumor secreted cytokines may enhance PDT-mediated toxicity of tumor associated endothelial cells.