TY - JOUR
T1 - Pharmacokinetics and tissue distribution of N-(2-hydroxyphenyl)-2-propylpentanamide in Wistar Rats and its binding properties to human serum albumin
AU - Correa-Basurto, Ana María
AU - Romero-Castro, Aurelio
AU - Correa-Basurto, José
AU - Hernández-Rodríguez, Maricarmen
AU - Soriano-Ursúa, Marvin Antonio
AU - García-Machorro, Jazmin
AU - Tolentino-López, Luis Esteban
AU - Rosales-Hernández, Martha Cecilia
AU - Mendieta-Wejebe, Jessica Elena
N1 - Publisher Copyright:
© 2018
PY - 2019/1/5
Y1 - 2019/1/5
N2 - N-(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 silico, UV and Raman spectroscopy data showed weak interactions between the test compound and human serum albumin. Thus, the results that were obtained demonstrated that despite its low oral bioavailability, the potential anticancer agent HO-AAVPA exhibits acceptable pharmacokinetic properties that would allow it to reach its site of action and exert its pharmacological effect in Wistar Rats, and it has a convenient profile for future assays to evaluate its human applications.
AB - N-(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 silico, UV and Raman spectroscopy data showed weak interactions between the test compound and human serum albumin. Thus, the results that were obtained demonstrated that despite its low oral bioavailability, the potential anticancer agent HO-AAVPA exhibits acceptable pharmacokinetic properties that would allow it to reach its site of action and exert its pharmacological effect in Wistar Rats, and it has a convenient profile for future assays to evaluate its human applications.
KW - Antitumor
KW - Docking
KW - Pharmacokinetics
KW - Protein binding
KW - Valproic acid derivative
UR - http://www.scopus.com/inward/record.url?scp=85053428189&partnerID=8YFLogxK
U2 - 10.1016/j.jpba.2018.09.010
DO - 10.1016/j.jpba.2018.09.010
M3 - Artículo
C2 - 30236821
SN - 0731-7085
VL - 162
SP - 130
EP - 139
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
ER -