title: Pharmacokinetic study of Growth Hormone-Releasing Peptide 6 (GHRP-6) in nine male healthy volunteers.
abstract: GHRP-6 is a growth hormone secretagogue that also enhances tissue viability in different organs. In the present work, we studied the pharmacokinetics of this short therapeutic hexapeptide (His-(D-Trp)-Ala-Trp-(D-Phe)-Lys-NH(2,) MW=872.44 Da) in nine male healthy volunteers after a single intravenous bolus administration of 100, 200 and 400 μg/kg of body weight. GHRP-6 was quantified in human plasma by a specific LC-MS method, previously developed and validated following FDA guidelines, using (13)C(3)Ala-GHRP-6 as internal standard (Gil et al., 2012, J. Pharm. Biomed. Anal. 60, 19-25). The Lower Limit of Quantification (5 ng/mL) was reached in all subjects at 12h post-administration, which was sufficient for modeling a pharmacokinetic profile including over 85% of the Area under the Curve (AUC). Disposition of GHRP-6 best fitted a bi-exponential function with R(2) higher than 0.99, according to a mathematic modeling and confirmed by an Akaike index (AIC) lower than that of the corresponding one-compartment model for all subjects. Averaging all three dose levels, the distribution and elimination half-life of GHRP-6 were 7.6 ± 1.9 min and 2.5 ± 1.1h, respectively. These values are coherent with existing data for other drugs whose disposition also fits this model. Dose dependence analysis revealed a noticeable trend for AUC to increase proportionally with administered dose. Atypical GHRP-6 concentration spikes were observed during the elimination phase in four out of the nine subjects studied.
authors.affiliation: Department of Chemical Synthesis, Center for Genetic Engineering and Biotechnology, PO Box 6162, Havana, Cuba.
authors.forename: Ania
authors.initials: A
authors.lastname: Cabrales
authors.forename: Jeovanis
authors.initials: J
authors.lastname: Gil
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernández
authors.forename: Carmen
authors.initials: C
authors.lastname: Valenzuela
authors.forename: Francisco
authors.initials: F
authors.lastname: Hernández
authors.forename: Idrián
authors.initials: I
authors.lastname: García
authors.forename: Ariadna
authors.initials: A
authors.lastname: Hernández
authors.forename: Vladimir
authors.initials: V
authors.lastname: Besada
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Reyes
authors.forename: Gabriel
authors.initials: G
authors.lastname: Padrón
authors.forename: Jorge
authors.initials: J
authors.lastname: Berlanga
authors.forename: Gerardo
authors.initials: G
authors.lastname: Guillén
authors.forename: Luis Javier
authors.initials: LJ
authors.lastname: González
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D013007:Growth Hormone-Releasing Hormone; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide; D013007:Growth Hormone-Releasing Hormone