This study aimed to determine whether the challenge from Escherichia coli ( E. coli ) lipopolysaccharide ( LPS ) affects the pharmacokinetics of danofloxacin in broilers. Twenty 1-day-old Arbor Acres ( AA ) broilers were equally and randomly divided into 2 groups. When the chickens were 23, 25, 27, and 29 days old, E. coli LPS (1 mL; 0.5 mg/kg body weight [ BW ]) and sterile saline (1 mL) were intraperitoneally injected into the two groups. After the last injection, danofloxacin was given to all chickens by gavage at the dose of 5 mg/kg BW. Then serum and plasma samples at each time point were collected through the wing vein. Danofloxacin concentrations in plasma were detected through the high-performance liquid chromatography ( HPLC ) method and subjected to noncompartmental analysis using Phoenix software. The levels of chicken interleukin-1β ( IL-1β ) and corticosterone ( CORT ) in serum were measured by the Enzyme-linked immunosorbent assay ( ELISA ) kit. In addition, after the collection of plasma or serum samples, 7 chickens (31 days of age) in each group were killed to calculate the organ indices. Compared with the control group, the challenge of LPS significantly decreased the parameters of AUC 0-∞ , C max , and t 1/2λz and increased the parameters of T max and λz. Additionally, in the LPS group, the absorption time of danofloxacin was prolonged; however, the elimination was accelerated, which resulted in reduced internal exposure.
The pharmacokinetics and tissue distribution of enrofloxacin were determined in Yellow River carp (Cyprinus carpio haematopterus) reared at 20°C after single oral administration of enrofloxacin at 10 mg·kg−1 body weight (BW). Plasma, bile, and different tissue samples, including liver, kidney, gill, gut, and skin-muscle, were collected at predetermined times points. An HPLC method was developed to simultaneously determine the concentrations of enrofloxacin and its metabolite, ciprofloxacin. However, ciprofloxacin was only detectable in some liver samples with trace levels. Then the average enrofloxacin concentrations vs. time data were subjected to a non-compartmental analysis using WinNonLin 5.2 software. Multiple peaking profiles were observed in all enrofloxacin concentration-time curves. The peak concentration (Cmax) values were observed as 0.79, 1.01, 2.09, 2.85, 4.34, 10.78, and 13.07 μg·ml−1 (or g−1) in plasma, skin-muscle, gill, kidney, liver, bile, and gut, respectively, and the corresponding time to reach peak concentration (Tmax) was 8, 8, 1, 8, 1, 72, and 4 h, respectively. The values of elimination half-life (T1/2λZ) of enrofloxacin in different tissues was in the following order: gill (291.13 h) > liver (222.29 h) > kidney (157.22 h) > plasma (129.44 h) > gut (91.47 h) > skin-muscle (87.77 h) > bile (86.22 h). The present results showed that enrofloxacin had a wide distribution in different tissues, however slow absorption and elimination in Yellow River carp. Additionally, enrofloxacin exhibited large distribution in bile, indicating that bile excretion might be the primary elimination route of enrofloxacin in Yellow River carp. A withdrawal period was calculated as 379.2 °C-day for single oral dosing of enrofloxacin at 10 mg/kg BW. Based on the calculated PK/PD indices of AUC/MIC or Cmax/MIC, the current enrofloxacin dosing regimen might have a positive therapeutic effect on the infection of Flavobacterium columnare, Aeromonas sobria, or Aeromonas hydrophila. However, the depletion study following multiple oral doses should be carried out in Yellow River carp reared at lower temperatures, and the withdrawal period should also be further calculated.
The objective of this study was to determine the pharmacokinetics of meloxicam after a single intravenous (IV), intramuscular (IM), and oral (PO) dose at 1 mg/kg body weight in Jing Hong laying hens. Blood samples were collected at predetermined time points. Plasma meloxicam concentrations were determined using a validated high‐performance liquid chromatography (HPLC) assay method and then subjected to a non‐compartmental analysis. After IV administration, meloxicam had a mean (±SD) volume of distribution at steady‐state (Vdss) of 206.50 ± 25.23 ml/kg, a terminal half‐life (t1/2λ) of 5.45 ± 0.53 h, and a total body clearance (Cl) of 26.48 ± 4.13 ml/h/kg. After PO and IM administration, meloxicam was absorbed relatively rapidly: the peak concentrations (Cmaxs) of 3.04 ± 0.56 and 8.94 ± 2.31 μg/ml were observed at 3.08 and 0.80 h, respectively. After PO and IM administration, the absolute bioavailability (F) was determined as 70.13% and 125.50%, respectively. Assuming that hens shared the same analgesic threshold of meloxicam (0.5 μg/ml) with humans, the plasma concentrations after three different routes (PO, IM, and IV) of administration were above this value for 16.7, 19.2, and 14.9 h, respectively.
Enrofloxacin (ENR) has been approved for the treatment of infections in aquaculture, but it may cause tissue residue. This research aimed to develop and validate a water temperature related PBPK model, including both ENR and ciprofloxacin (CIP), in rainbow trout, and to predict further their residue concentrations and the withdrawal periods for ENR at different water temperatures. With the published concentrations data, a flow-limited PBPK model including both ENR and CIP sub-models was developed to predict ENR and CIP concentrations in tissues and plasma/serum after intravenous, oral, or immersion administration. A Monte Carlo simulation including 500 iterations was further incorporated into this model. Based on the model and Monte Carlo analysis, the withdrawal intervals were estimated for different dosage regimens and at different water temperatures, ranging from 80 to 272 degree-days. All of these values were shorter than the labeled withdrawal period (500 degree-days) in fish. This model provided a useful tool for predicting the tissue residues of ENR and CIP in rainbow trout under different dosage regimens and at different water temperatures.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.