Pharmacokinetics of magnolol following different routes of administration to goldfish (Carassius auratus) and its oral efficacy against Ichthyophthirius multififiliis infection

Abstract

Magnolol is a promising lead compound for the development of commercial drug for the control of Ichthyophthirius multifiliis infection. However, a lack of information on pharmacokinetics of magnolol in fish limited the further application. Here, this study was to determine the pharmacokinetics in goldfish (Carassius auratus) following a single administration by oral (OR) gavage, intraperitoneal (IP) injection at a dose of 30 mg magnolol /kg fish and bath at 1.5 mg magnolol /L at 22 ± 1 °C. First, we found a mixture containing 1 mL of methanol-ethyl acetate (7: 3, v/v) and 5 μL hydrochloric acid for extraction of mangolol from 1 g of tissue or 1 mL of serum had satisfied recovery (>85%). Furthermore, the concentrations of magnolol in the serum, intestine, liver, kidney, muscle and gill were investigated by a high-performance liquid chromatography (HPLC). For all routes of administration, magnolol could be absorbed and distributed slowly. The results showed that the maximum serum concentration (Cmax) for OR, IP and bath administration were 0.89 mg·L −1, 0.2 mg·L −1 and 0.61 mg·L −1, with time to peak concentration (Tmax) were 8 h, 3 h and 10 h, respectively. The concentrations of magnolol in the serum, liver and intestine were below the limits of quantification at 72 h post-OR administration. Finally, the study investigated the efficacy of OR administration of magnolol against I. multifiliis infection. The results showed that OR of magnolol at a dose of 90 mg magnolol /kg fish per day for 3 days increased the survival rate (p = 0.0281) of goldfish, and decreased infection level (p < 0.0001) and incidence of infestation (p < 0.0001) of goldfish significantly. Our results may help in the use of magnolol in fish, and also indicate that OR administration of mangolol is a potential means for controlling I. multifiliis infection.