title: Pharmacokinetics in Wistar Rats of 5-[(4-Carboxybutanoyl)Amino]-2-Hydroxybenzoic Acid: A Novel Synthetic Derivative of 5-Aminosalicylic Acid (5-ASA) with Possible Anti-Inflammatory Activity.
abstract: 5-[(4-carboxybutanoyl)amino]-2-hydroxybenzoic acid (C2) is a novel synthetic derivative of 5-aminosalicylic acid (5-ASA), which is currently being evaluated ex vivo as an anti-inflammatory agent and has shown satisfactory results. This study aimed to obtain the pharmacokinetic profiles, tissue distribution and plasma protein binding of C2 in Wistar Rats. Additionally, an HPLC method was developed and validated to quantify C2 in rat plasma. The pharmacokinetic profiles of intragastric, intravenous and intraperitoneal administration routes at singles doses of 100, 50, and 100 mg/kg, respectively, were studied in Wistar rats. The elimination half-life of intravenously administered C2 was approximately 33 min. The maximum plasma level of C2 was reached approximately 24 min after intragastric administration, with a Cmax value of 2.5 g/mL and an AUCtot value of 157 μg min-1/mL; the oral bioavailability was approximately 13%. Following a single intragastric or oral dose (100 mg/kg), C2 was distributed and detected in all examined tissues (including the brain and colon). The results showed that C2 accumulates over time. The plasma protein binding results indicated that the unbound fraction of C2 at concentrations of 1 to 20 μg/mL ranged from 89.8% to 92.5%, meaning that this fraction of C2 is available to cross tissues. Finally, the blood-plasma partitioning (BP ratio) of C2 in rat plasma was 0.71 and 0.6 at concentrations of 5 and 10 μg/mL, respectively, which indicates that C2 is free in the plasmatic phase and not inside blood cells. The results of this study suggest that a fraction of the administered C2 dose is absorbed in the stomach, and the fraction that is not absorbed reaches the small intestine and colon. This distribution constitutes the main advantage of C2 compared with 5-ASA for the treatment of ulcerative colitis (UC) and Crohn's disease (CD).
authors.affiliation: Laboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México 11340, México.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Romero-Castro
authors.affiliation: Laboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México 11340, México.
authors.forename: Mara
authors.initials: M
authors.lastname: Gutiérrez-Sánchez
authors.affiliation: Laboratorio de Modelado Molecular y Bioinformática, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México 11340, México.
authors.forename: José
authors.initials: J
authors.lastname: Correa-Basurto
authors.affiliation: Laboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México 11340, México.
authors.forename: Martha Cecilia
authors.initials: MC
authors.lastname: Rosales Hernández
authors.affiliation: Laboratorio de Química Supramolecular y Orgánica, Departamento de Ciencias Básicas, Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional, Av. Acueducto s/n, Barrio La Laguna Ticomán, Ciudad de México 07340, México.
authors.forename: Itzia Irene
authors.initials: II
authors.lastname: Padilla Martínez
authors.affiliation: Laboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México 11340, México.
authors.forename: Jessica Elena
authors.initials: JE
authors.lastname: Mendieta-Wejebe
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring; D004355:Drug Stability; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine