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Bioavailability and kinetics of the antihypertensive casein-derived peptide HLPLP in rats

AutorSánchez-Rivera, Laura ; Ares, I.; Miralles, Beatriz ; Gómez-Ruiz, José Ángel ; Recio, Isidra ; Martínez-Larrañaga, M. R.; Anadón, A.; Martínez, Maria A.
Palabras claveTandem MS
Plasma disposition
Oral bioavailability
Antihypertensive peptide HLPLP
Fecha de publicación2014
EditorAmerican Chemical Society
CitaciónJournal of Agricultural and Food chemistry 62(49): 11869-11875 (2014)
ResumenThe aim of this study was to investigate the oral bioavailability and kinetics of the milk casein-derived peptide HLPLP, which had previously demonstrated antihypertensive effect in spontaneously hypertensive rats. HLPLP disposition after single intravenous (4 mg/kg body weight) and oral (40 mg/kg body weight) doses was studied in rats. Plasma concentrations of HLPLP [β-casein fragment f(134-138)], and two derived fragments found after HLPLP administration, LPLP [β-casein fragment f(135-138)] and HLPL [β-casein fragment f(134-137)], were determined by ultrahigh performance liquid chromatography (UPLC) coupled on line to a Q-TOF instrument. For HLPLP, the elimination half-lives (T1/2β) were 7.95 min after intravenous and 11.7 min after oral administration. The volume of distribution at steady state (Vss = 30.8 L/kg) suggests a considerable uptake of HLPLP into tissues. HLPLP was converted to the peptides LPLP and HLPL. After HLPLP intravenous administration, the elimination half-lives (T1/2β) for these biotransformed peptides, LPLP and HLPL, were 8.38 and 10.9 min, respectively. After oral administration, HLPLP was rapidly absorbed with an absorption half-life (T1/2a) of 2.79 min. The oral bioavailability of HLPLP was found to be 5.18%. Our study suggested that HLPLP was rapidly absorbed and eliminated after oral administration, biotransformed into smaller fragments LPLP and HLPL, and distributed throughout the body by the circulation blood. The present pharmacokinetic information from a preclinical kinetic study in rats can also play an important role in designing future kinetic studies in humans for assessing HLPLP dose-response relationship.
Identificadoresdoi: 10.1021/jf5035256
issn: 0021-8561
e-issn: 1520-5118
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