Pharmacokinetics and tissue distribution of N-(2-hydroxyphenyl)-2-propylpentanamide in Wistar Rats and its binding properties to human serum albumin

Publication date: Available online 5 September 2018Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Ana María Correa-Basurto, Aurelio Romero-Castro, José Correa-Basurto, Maricarmen Hernández-Rodríguez, Marvin Antonio Soriano-Ursúa, Jazmin García-Machorro, Luis Esteban Tolentino-López, Martha Cecilia Rosales-Hernández, Jessica Elena Mendieta-WejebeAbstractN-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) is a novel valproic acid derivative that has shown anti-proliferative activity against epitheloid cervix carcinoma (HeLa), rhabdomyosarcoma (A204), and several breast cancer cell lines. The aim of this research was to evaluate the pharmacokinetic profile and tissue distribution of HO-AAVPA in Wistar rats, as well as its human serum albumin binding potential by experimental and in silico methods. A single dose of HO-AAVPA was given to male rats by intravenous, intragastric or intraperitoneal routes at doses of 25, 100, and 100 mg/kg, respectively. Then, blood samples were drawn at predetermined intervals of time, and the HO-AAVPA concentration in the plasma was quantified with a validated HPLC method. The elimination half-life (t1/2) was approximately 222 min, and the systemic clearance (CL) and apparent volume of distribution (Vd) were 2.20 mL/min/kg and 0.70 L/kg, respectively. The absolute oral bioavailability of HO-AAVPA was 33.8%, and the binding rate of HO-AAVPA with rat plasma proteins was between 66.2% and 83.0%. Additionally, in sili...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research