title: Effect of severe protein-calorie malnutrition on the penetration kinetics of trimethoprim and sulfamethoxazole to the deep tissues of Wistar rats.
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.
authors.affiliation: Department of Pharmacology, National Institute of Pediatrics-SSA, Colonia Insurgentes Cuicuilco, México City. ismaelares@yahoo.com
authors.forename: Ismael
authors.initials: I
authors.lastname: Lares-Asseff
authors.forename: Maria Gabriela
authors.initials: MG
authors.lastname: Pérez
authors.forename: Guadalupe A
authors.initials: GA
authors.lastname: Camacho
authors.forename: Alejandra R
authors.initials: AR
authors.lastname: Toledo
authors.forename: Maria
authors.initials: M
authors.lastname: del Carmen López
authors.forename: Adrián J
authors.initials: AJ
authors.lastname: Guillé
authors.forename: Martha G
authors.initials: MG
authors.lastname: Sosa
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004044:Dietary Proteins / Q000008:administration & dosage; D004334:Drug Administration Schedule; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D044342:Malnutrition; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000378:metabolism; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000890:Anti-Infective Agents; D004044:Dietary Proteins; D015662:Trimethoprim, Sulfamethoxazole Drug Combination