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 12 h 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 ± 1.1 h, 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.