The Complete Analysis of the Distribution Kinetics of the Oxytetracycline Antibiotic in the Exoskeleton of Farmed Pacific White Shrimp,Litopenaeus vannamei

Oxytetracycline (OTC) in shrimp shells may be dispersed to the environment as shrimp shred old cuticle in growout ponds. The study aims to assess the kinetics of OTC accumulated in shrimp shell. Sub‐adult male Litopenaeus vannamei in the C–D₀ molting stage, were force fed with medicated feeds at various accurate dose levels that included 50, 500 and 1000 mg/kg‐body weight (BW). In addition to hemolymph, hepatopancreas and muscle were serially collected for 50 mg/kg‐BW‐dose group while cuticle was sampled for higher dose levels. All were assayed for OTC by a validated high‐performance liquid chromatography (HPLC) method. Mineral contents in shell samples of 500 mg/kg‐BW‐dose were also determined. The bioavailability markedly decreased with increasing dose due to incomplete dissolution and/or mild dysfunction in absorption. Administered doses, 2.69 and 2.25%, ended up in the shell after dosing with 500 and 1000 mg/kg‐BW, respectively. OTC data after a dose of 50 mg/kg‐BW was fitted into a three‐compartment model with an added shell compartment with r² of 0.9920. The model was successfully extrapolated to predict OTC distribution in shell at higher doses. In addition, there was evidence that OTC may disturb the biomineralization process via complex formation with calcium and magnesium lowering the exoskeleton mineral contents.     

Physicochemical properties and in vitro antioxidant activities of pyroligneous acid prepared from brushwood biomass waste of Mangosteen,Durian, Rambutan,and Langsat

Physicochemical characteristics and in vitro antioxidant activities of four pyroligneous acids carbonized from the wastes of wood species including Mangosteen (Garcinia mangostana Linn.), Durian (Durio zibethinus L.), Rambutan (Nephelium lappaceum L.), and Langsat (Lansium domesticum Serr.) were assessed. Appearing as transparent liquors with pH 3.9–4.2, the pyroligneous acid samples under test possessed acetic acid (23.22–25.46%) as the dominant component. The total soluble tar, total acid, and water content were 0.15 - 0.28 wt%, 99–192 mg KOH/g and 84.5–93.5 wt%, respectively. Phenolic compounds namely: 2,6-dimethoxyphenol (6.88–9.69%),phenol (2.97–5.88%), 4-methylsyringol (3.10–3.56%), guaiacol (2.36–3.55%), and 2-methoxy-4-methylphenol (1.08–1.28%) were found. All had in vitro antioxidant activities especially mangosteen pyroligneous acid, which showed activity roughly similar to BHT (P>0.05) against anti-lipid peroxidation. Nitric oxide scavenging capacities of all pyroligneous acids were significantly higher than BHT (P<0.05). Our results suggest that pyroligneous acids from the four types of branch waste could be used as sources of beneficial natural antioxidants, possibly as food or feed additives to protect against lipid peroxidation, and potentially also in veterinary medicine in anti-inflammatory products.     

The in vitro efficacy of oxytetracycline against re‐isolated pathogenic Aeromonas hydrophila carrying the cytolytic enterotoxin gene through hybrid catfish,Clarias macrocephalus (Günther, 1864) × Clarias gariepinus (Burchell, 1822) in Thailand

Aeromonas hydrophila is a pathogen infecting farmed hybrid catfish, Clarias macrocephalus (Günther, 1864) × Clarias gariepinus (Burchell, 1822) which incurs substantial economic losses in Thailand. The study aimed at a genetic tracking of A. hydrophila infection and the in vitro assessment of the efficacy of antibiotics against its virulent strains. Five clinical strains from catfishes and Nile tilapia were employed. They were 3‐passage re‐isolated through healthy hybrid catfish and the cytolytic enterotoxin gene (AHCYTOEN) of individuals was traced. Each of the re‐isolates at a dose of ~6.67 × 10⁵ CFU/g was intraperitoneally injected into ~15 g‐healthy hybrid catfish and their pathogenicity were observed for 7 days. It was found that AHCYTOEN was carried over whereas typical signs of motile aeromonas septicaemia were found in the specimens. The bacterial strains of Nile tilapia origin did not induce mortality but those of catfish origins (80%–100% rate of mortality). The strains were susceptible to the tetracycline antibiotics, and oxytetracycline produced MIC₅₀ and MBC as low as 0.007–0.031 μg/ml and 1–8 μg/ml respectively. As oxytetracycline specifically inhibited pathogenic A. hydrophila in vitro, it is recommended that an appropriate dosage regimen of the drug should be established.     

A Toxicokinetic Study of Oxytetracycline Antibiotics in Farmed Pacific White Shrimp,Penaeus vannamei

Toxicokinetics has demonstrated abnormal signs in drug distribution/disposition without waiting until the drug damages the tissues/organs. It is a study of the kinetic assessment of administering high‐dose of oxytetracycline (OTC) to white shrimp. Male Penaeus vannamei in the C–D₀ molting stage, were force fed with medicated feeds at various accurate dose levels including 500, 1000, and 2500 mg/kg‐body weight (BW). After dosing with different time intervals, hemolymph, muscle, and hepatopancreas were collected, and assayed for OTC by validated high‐performance liquid chromatography method. The simulated profile based on the maximum recommended dose was tested to approach the systemic level where the drug was anticipated not to cause significant toxic responses. OTC kinetic profiles in the hemolymph were fitted into the flow limited model having r² value between 0.8341 and 0.9373. The relative affinities for the muscle and hepatopancreas changed at dose level exceeding 1000 mg/kg BW. Although hepatopancreatic clearance was non‐linearly related with dose, the persistence of OTC in muscle after 2500 mg/kg BW dosing was observed to indicate abnormalities in drug distribution/disposition. It was hypothesized that the pharmacokinetic alteration after extreme dosing was because of induction of functional abnormalities in hepatopancreas. In addition, a single administration of OTC at 1000 mg/kg BW was anticipated to be a tolerated dose.     

Hepatopancreatic and muscular distribution of oxytetracycline antibiotics in farmed pacific white shrimp (Penaeus vannamei): a physiological‐based pharmacokinetic model approach

Oxytetracycline (OTC) pharmacokinetic models previously used to investigate Penaeus vannamei have not addressed the specific problems related to drug distribution/disposition in particular tissues. This study aimed to provide an insight into OTC kinetics in the hepatopancreas and muscle based on a physiological model approach. Adult male P. vannamei at the C‐D₀ inter‐moulting stage were randomly assigned to intra‐sinus and oral administrations. In the intra‐sinus group, shrimps were dosed via the ventral sinus at an OTC level of 10.0 μg g^?1 body weight, while in the oral one, they were force fed at a dose level of 50.2 μg g^?1. The medicated animals were sampled at various time intervals until 170 h after dosing. Haemolymph, muscle and hepatopancreas samples were taken and OTC levels were determined using the validated HPLC method. A model focused on the hepatopancreas and muscle was developed. Oxytetracycline pharmacokinetic profiles in particular tissues were fitted into the model with an R² of between 0.6568 and 0.9904. Oxytetracycline muscular distributions were essentially identical for both groups and the drug did not accumulate in muscle. The distributions in the hepatopancreas for both groups were extensive, whereas that for oral administration was approximately 2.3 times greater than that for the intra‐sinus one. It was demonstrated that hepatopancreatic OTC may undergo significant first‐pass elimination with non‐linear kinetics.     

The complete analysis of oxytetracycline pharmacokinetics in farmed Pacific white shrimp (Litopenaeus vannamei)

Lack of dosing information of the major antibiotics known as oxytetracycline (OTC) for the Pacific white shrimp (Litopenaeus vannamei) could have harmful impact on aquaculture in Thailand. The aim of this study was to detail complete pharmacokinetic information of OTC in the Pacific white shrimp. Sixty-four male L. vannamei weighing 14-22 g with carapace length of 2.30-3.00 cm in the standardized moulting stage of C-D(0) were used for the investigations. Single dose, 10 microg/g body weight OTC solution was administered intra-sinusally (i.s.), and the shrimps were then sampled in three replicates at time intervals of 0.25, 0.5, 2, 4, 6, 9, 12, 24, 48, 72, 170, 336 and 504 h postdose. OTC levels with time intervals in biological matrices including the hemolymph, abdominal muscle, and digestive gland of each sample were determined by validated high-performance liquid chromatography, and were analyzed with noncompartment and compartment models. A simplified two-compartment model was employed rather than a more complicated model, with additional digestive compartment if necessary. A significant portion of the OTC was found in the digestive glands, even though the OTC was administered i.s. The model indicated that the OTC was thus not only distributed into the tissue compartment, but also to the digestive gland, from where it was eliminated from the shrimp's body. The dispositional half-lives of all compartments was found to be 14-21 h. Approximately 60% of the drug elimination took place in digestive gland, which is proposed to be the major route of elimination.