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

Aurelio Romero-Castro, Mara Gutiérrez-Sánchez, José Correa-Basurto, Martha Cecilia Rosales Hernández, Itzia Irene Padilla Martínez, Jessica Elena Mendieta-Wejebe

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Abstract

© 2016 Romero-Castro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 5-[(4-carboxybutanoyl)amino]-2-hydroxybenzoic acid (C.2) 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 μgmin-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
Original languageAmerican English
JournalPLoS ONE
DOIs
StatePublished - 1 Jul 2016

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