Related Experiment Video
Updated: May 1, 2026
Subcutaneous Neurotrophin 4 Infusion Using Osmotic Pumps or Direct Muscular Injection Enhances Aging Rat Laryngeal Muscles
Published on: June 13, 2017
Pharmacokinetics and safety of human recombinant hepatocyte growth factor administered to vocal folds
Masanobu Mizuta1, Shigeru Hirano, Yo Kishimoto
1Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto.
Objectives/Hypothesis:
Previous animal studies demonstrated that hepatocyte growth factor (HGF) has the potential to regenerate scarred vocal folds. In addition, HGF is now produced under a good manufacturing practice (GMP) procedure. Therefore, human clinical trials of HGF are warranted in patients with vocal fold scarring. In the current study, we investigated the pharmacokinetics and the local tissue responses of HGF administered to rat vocal folds.
Study Design:
Prospective animal experiment.
Methods:
Five μg of recombinant human HGF was administered to the vocal folds of Sprague-Dawley rats (n = 60) using a microsyringe. The concentration of HGF in larynges and blood was investigated by enzyme-linked immunosorbent assay. To evaluate the local tissue responses caused by HGF administration, endoscopic and histological examinations were performed.
Results:
HGF concentration in the larynges was 50.1 μg/g tissue 5 minutes after administration. The concentration decreased rapidly to 1.71 μg/g tissue at 12 hours after administration and to 0.29 ng/g tissue at 24 hours after administration. Seven days after administration, HGF concentration was minimal in one-half of the cases and was not detected in the other cases. Transmission of HGF to blood was detected in two of six cases at 5 minutes after administration, but was no longer detected 12 hours later. Endoscopic and histological examinations revealed no edema or erythema of the vocal folds in any of the cases.
Conclusions:
The current results contribute to the safety and pharmacokinetic management of future clinical trials using HGF administered to vocal folds.
