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1.
Mech Ageing Dev ; 127(1): 73-8, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16298418

ABSTRACT

UNLABELLED: Acetylation capacity during drug metabolism differs between species, gender and age groups. OBJECTIVE: The purpose of this work was to determine variations in the acetylating phenotype (AP), in a longitudinal study, as a function of growth and development. METHODS: Twenty male Wistar rats were studied. AP was determined on days 21, 48, 114, 180, 457 and 780 with oral doses of 30mg/kg of sulphadiazine (SDZ) by urine collection. The Schröeder and Vree methods were used to obtain SDZ concentrations, both acetylated and not acetylated. Rats were classified as slow or fast acetylators in accordance with previously validated metabolic indicators. RESULTS: Of the 20 rats phenotyped at 21 and 48 days of age, 18 were slow and 2 were fast acetylators. As age and consequent growth progressed, changes in the expression of AP were registered. At 114 days, 16 rats were slow and 4 were fast acetylators; at 180 days, 12 were slow and 8 were fast; at 457 days, 6 were slow and 14 were fast; at 780 days, the 20 rats were fast acetylators. Slow acetylation predominates at younger ages. CONCLUSIONS: The effect of growth and developmental progress on AP is evident and relates to previous reports of changes in AP, determined by age in animal and human models. The relevance of changes determined by growth and development should be considered in rational drug management.


Subject(s)
Aging/metabolism , Sulfadiazine/metabolism , Acetylation , Aging/drug effects , Animals , Longitudinal Studies , Male , Phenotype , Rats , Rats, Wistar , Sulfadiazine/administration & dosage , Time Factors
2.
J Pharm Pharmacol ; 55(4): 469-77, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12803768

ABSTRACT

This study shows the effect that severe malnourishment has on the kinetics of antibiotic penetration in tissues. A total of 104 male Wistar rats, 21 days old, were randomly divided into eight groups. Five groups of experimental rats were severely malnourished (SM) and three further groups were considered well-nourished control groups (WN). A single dose of trimethoprim-sulfamethoxazole (TMP-SMX) was administered intraperitoneally. Blood samples were taken by heart puncture and five organs were extracted 0-24 h after the administration of the drug. HPLC was used to assess the amount of trimethoprim and sulfamethoxazole in fluids. The elimination half-life for trimethoprim from plasma was longer in SM rats with a median of 3.15 h; in WN rats, it was 0.390 h. Clearance was slower in SM rats: 646.72 mL microg(-1) h(-1) vs 3036.38 mL microg(-1) h(-1) in WN rats (P < 0.05). Tissue penetration was much higher for trimethoprim, with penetration indexes of 0.80-5.66 in WN rats, compared with 0.35-2.14 in SM rats. In the case of sulfamethoxazole, penetration indexes were 0.029-1.13 for WN and 0.075-0.657 for SM rats. Similarly, the penetration ratio to muscle and heart tissue was lower in SM rats. However, penetration to kidney, lung, liver and spleen was greater in SM rats. It is evident that severe SM decreases the capacity of trimethoprim more importantly than sulfamethoxazole biotransformation.


Subject(s)
Anti-Infective Agents/pharmacokinetics , Malnutrition , Trimethoprim, Sulfamethoxazole Drug Combination/pharmacokinetics , Animals , Anti-Infective Agents/administration & dosage , Chromatography, High Pressure Liquid , Dietary Proteins/administration & dosage , Drug Administration Schedule , Injections, Intraperitoneal , Kidney/metabolism , Liver/metabolism , Lung/metabolism , Male , Rats , Rats, Wistar , Spleen/metabolism , Trimethoprim, Sulfamethoxazole Drug Combination/administration & dosage
3.
Rev. gastroenterol. Méx ; Rev. gastroenterol. Méx;64(4): 159-66, oct.-dic. 1999. tab, graf
Article in Spanish | LILACS | ID: lil-276257

ABSTRACT

Antecedentes: la anemia es un problema hematológico prevalente en ancianos, que afecta a 14 por ciento de los hombres y a 6 por ciento de las mujeres de la población mayor de 60 años de edad en México. Objetivo: determinar el efecto de la administración prolongada de fumarato ferroso en ancianos con deficiencia de hierro. Método: se estudió una población de 178 ancianos con edades entre 65 y 100 años, en 51 de estos sujetos (28.65 por ciento) se diagnosticaron niveles séricos anormales de hierro, menores de 80m g/dL para los hombres y 60 m g/dL para las mujeres, únicamente 21 de estos ancianos (11.8 por ciento) aceptaron participar en el estudio, en los cuales se estudió la respuesta a la administración oral de 5 mg/kg de hierro elemental durante seis meses.Los pacientes fueron clasificados según la alteración de los parámetros del metabolismo del hierro en tres grupos. (grupo 1 = 10.9 por ciento anemia; grupo 2 = 28.0 por ciento y grupo 3 = 63.0 por ciento de anemia). Resultados: la eficacia del tratamiento se evaluó por los cambios ocurridos en los parámetros hematológicos, como concentración de hierro sérico, hemoglobina, ferritina e índice de saturación, a los 0, 30, 90 y 180 días. Se observó que el tratamiento con fumarato ferroso durante seis meses produjo mejoría en la población estudiada determinada por el incremento significativo en los valores de los parámetros del metabolismo del hierro.Conclusiones: los resultados de este estudio sugieren la utilidad del tratamiento prolongado con fumarato ferroso en pacientes ancianos con deficiencia de hierro, para evitar fallas terapéuticas como consecuencia del no cumplimiento, el cual es común en ellos


Subject(s)
Humans , Male , Female , Aged , Ferrous Compounds/administration & dosage , Ferrous Compounds/therapeutic use , Fumarates/administration & dosage , Fumarates/therapeutic use , /drug therapy , Anemia, Iron-Deficiency/drug therapy
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