Pharmacokinetic study of Vibrio parahaemolyticus phage Фvp140 in Litopenaeus vannamei following oral administration

Bacteriophages (phages) are natural predators of bacteria, and have been shown to be potential alternatives to antibiotics in the prevention and treatment of bacterial infections of shrimp. In order to understand whether phages can effectively reach the site of infection, the pharmacokinetics of Vibrio parahaemolyticus phage Фvp140 in Litopenaeus vannamei was investigated following oral administration by gavage and via medicated feed. Whether administered by gavage or via medicated feed, phage Фvp140 could be rapidly distributed to various tissues of shrimp. The phage titer was the highest in the intestine, followed by the hepatopancreas, whose phage titer was about 10 % of that in the intestine, and only a small amount of phages could enter the circulatory system. A simple exponential decay model could effectively describe the elimination of phages in each tissue, and the higher the dose, the faster the elimination rate. The elimination rate of the phage in the hepatopancreas was the fastest, while the elimination rate of the phage in the intestine was similar to (by oral gavage) or faster than (via medicated feed) that in hemolymph. After oral gavage at three doses, the phage titers in shrimp tissues showed a dose-dependent relationship. This study found that after oral administration of phages, a large number of phages could directly into the hepatopancreas. Although the phage eliminated quickly，the continuous oral administration of phages in shrimp via medicated feed enabled the maintenance of a high level of phage titers in the hepatopancreas. This study provided pharmacokinetic evidence for the application of phage in shrimp farming and laid the foundation for further optimization of bacteriophage therapy.