In vitro antibacterial activity of danofloxacin against Escherichia coli isolated from pigeons and its pharmacokinetic in pigeons.

This experiment aimed to investigate the in vitro antimicrobial activity of danofloxacin against Escherichia coli (E. coli) isolated from pigeons, as well as the pharmacokinetics of danofloxacin in pigeons following oral (PO), intramuscular (IM), and intravenous (IV) administration. The minimum inhibitory concentration (MIC) of danofloxacin was first determined for 38 clinical E. coli strains using the micro broth dilution method. Subsequently, 30 healthy pigeons were weighed and randomly divided into 3 groups: IM, IV, and PO, with 10 pigeons in each group. Danofloxacin was given at 5 mg/kg body weight (BW) through 3 different routes. Blood was collected, and plasma was separated at various time points from 0 to 48 h. Plasma samples were analyzed for danofloxacin concentrations using a validated HPLC method. Pharmacokinetic analysis was performed using Phoenix software and a noncompartmental analytical (NCA) method. The results indicated that danofloxacin had a strong antibacterial effect on E. coli, with a MIC50 of 0.5 µg/mL. The noncompartmental analysis showed that after PO and IM administration at 5 mg/kg in pigeons, peak plasma concentrations (Cmax) of 0.61 and 1.62 µg/mL were reached at 4.5 and 0.53 h, respectively. The oral and intramuscular bioavailability (F) were 68.08% ± 24.82% and 87.82% ± 25.36%, respectively. Following IV administration, danofloxacin was widely distributed in pigeons, with volume of distribution (VZ) and volume of distribution at steady state (VSS) values of 6.11 ± 2.01 and 4.65 ± 1.62 L/kg, respectively, and was eliminated slowly, with an elimination half-life (t1/2λz) of 6.41 ± 2.15 h. Based on the calculated ratio values of AUC/MIC, the current IV, IM, and PO doses of 5 mg/kg of danofloxacin would be expected to effectively treat pigeons infected with E. coli strains with MIC values equal to or less than 0.5 µg/mL.

Liver involvement with Langerhans cell histiocytosis in adults.

BACKGROUND AND AIMS: Liver involvement portends poor prognosis in adults. We aimed to characterize the clinical features, liver function tests, radiologic findings, molecular profiles, therapeutic approaches and outcomes of adults patients with Langerhans cell histiocytosis (LCH) with liver involvement. METHODS: We conducted a retrospective analysis of all adults with LCH (≥ 18 years) seen at Peking Union Medical College Hospital (Beijing, China) between January 2001 and December 2022. RESULTS: Among the 445 newly diagnosed adults with LCH, 90 patients had liver involvement at diagnosis and 22 patients at relapse. The median age was 32 years (range, 18-66 years). Of 112 evaluable patients, 108 had full liver function testing, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), and total bilirubin and albumin. Elevated ALP was seen in 63.0% and GGT in 86.1%; 14.8% had elevated bilirubin. Next-generation sequencing of 54 patients revealed frequent BRAFN486_P490 (29.6%), BRAFV600E (18.5%), and MAP2K1 (14.8%). OUTCOMES: After a median 40 months' follow-up (range 1-168 months), 3-year progression-free survival (PFS) and overall survival were 49.7% and 86.6% respectively. In multivariable analyses, ≥3 abnormal liver function tests (HR 3.384, 95% CI 1.550-7.388, P = .002) associated with inferior PFS; immunomodulatory drug therapy (HR 0.073, 95% CI, 0.010-0.541, P = .010) correlated with superior PFS versus chemotherapy. CONCLUSIONS: In summary, elevated GGT and ALP were common in adults with LCH liver involvement. Greater than equal to 3 abnormal liver function tests predicted poor outcomes. Immunomodulatory drug therapy was associated with favorable progression-free survival compared to chemotherapy.

Palladium/Platinum/Ruthenium Trimetallic Dendritic Nanozymes Exhibiting Enhanced Peroxidase-like Activity for Signal Amplification of Lateral Flow Immunoassays.

Developing ultrasensitive lateral flow immunoassays (LFIAs) has garnered significant attention in the field of point-of-care testing. In this study, a trimetallic dendritic nanozyme (Pd@Pt-Ru) was synthesized through Ru deposition on a Pd@Pt core and utilized to enhancing the sensitivity of LFIAs. Pd@Pt-Ru exhibited a Km value of 5.23 mM for detecting H2O2, which indicates an H2O2 affinity comparable with that of horseradish peroxidase. The Ru surface layer reduces the activation energy barrier, which increases the maximum reaction rate. As a proof of concept, the proposed Pd@Pt-Ru nanozyme was incorporated into LFIAs (A-Pd@Pt-Ru-LFIAs) for detecting human chorionic gonadotropin (hCG). Compared with conventional gold nanoparticle (AuNP)-LFIAs, A-Pd@Pt-Ru-LFIAs demonstrated 250-fold increased sensitivity, thereby enabling a visible detection limit as low as 0.1 IU/L. True positive and negative rates both reached 100%, which renders the proposed Pd@Pt-Ru nanozyme suitable for detecting hCG in clinical samples.

Safety and efficacy of flumatinib as later-line therapy in patients with chronic myeloid leukemia.

To evaluate the efficacy and safety of flumatinib in the later-line treatment of Chinese patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia (CP-CML previously treated with tyrosine kinase inhibitors (TKIs). Patients with CML-CP were evaluated for the probabilities of responses including complete hematologic response (CHR), cytogenetic response, and molecular response (MR) and adverse events (AEs) after the later-line flumatinib therapy. Of 336 enrolled patients with median age 50 years, median duration of treatment with flumatinib was 11.04 (2-25.23) months. Patients who achieved clinical responses at baseline showed maintenance of CHR, complete cytogenetic response (CCyR)/2-log molecular response (MR2), major molecular response (MMR), and 4-log molecular response or deep molecular response (MR4/DMR) in 100%, 98.9%, 98.6%, and 92.9% patients, respectively. CHR, CCyR/MR2, MMR, and MR4/DMR responses were achieved in 86.4%, 52.7%, 49.6%, and 23.5% patients respectively, which showed the lack of respective clinical responses at baseline. The patients without response at baseline, treated with flumatinib as 2L TKI, having no resistance to prior TKI or only resistance to imatinib, with response to last TKI, and with BCR::ABL ≤10% had higher CCyR/MR2, MMR, or MR4/DMR. The AEs observed during the later-line flumatinib treatment were tolerable and consistent with those reported with the first-line therapy. Flumatinib was effective and safe in patients who are resistant or intolerant to other TKIs. In particular, 2L flumatinib treatment induced high response rates and was more beneficial to patients without previous 2G TKI resistance, thus serving as a probable treatment option for these patients.

Sirolimus is effective for refractory/relapsed idiopathic multicentric Castleman disease: A single-center, retrospective study.

Refractory/relapsed idiopathic multicentric Castleman disease (R/R iMCD) has limited treatment options. With studies showing increased mTOR activation in iMCD patients, sirolimus becomes an attractive and promising therapy for R/R iMCD. Here we report the results of a retrospective study involving 26 R/R iMCD patients treated with sirolimus-containing regimen. The median age at sirolimus initiation was 40.5 years (23-60), with a median prior treatment line of 2 (1-5). 18 patients (69.2%) achieved symptomatic and biochemical response, with a median time to at least overall partial remission of 1.9 months (0.5-14.6). The median follow-up time from sirolimus initiation was 11.7 months (1.6-50.7) and the median time to next treatment (TTNT) was 46.2 months. No patients died at the end of follow-up. Most of the patients in the cohort are in ongoing responses and continue sirolimus therapy. Sirolimus is well tolerated with minor adverse effects. In conclusion, sirolimus is effective for R/R iMCD patients with good tolerance.

Research Note: Pharmacokinetics of bromhexine hydrochloride in broilers after single oral and intravenous administration.

The current study aimed to investigate the pharmacokinetics of bromhexine hydrochloride in broilers after single intravenous (IV) and oral (PO) administration at 2.5 mg/kg body weight (BW). The trial adopted a randomized, parallel-controlled design, where 20 twelve-wk-old broilers were randomly assigned to either the PO or IV group. Blood samples were collected at predetermined time points, and plasma was further separated for analysis. The bromhexine hydrochloride concentrations in plasma samples were determined using an ultra-performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) method. Noncompartmental analysis (NCA) using Phoenix software was conducted to analyze the concentration versus time data of bromhexine hydrochloride in every chicken. Subsequently, the main pharmacokinetic parameters between the 2 groups were statistically analyzed using SPSS software. Results from NCA revealed that after oral administration at 2.5 mg/kg BW, bromhexine hydrochloride exhibited slow absorption, reaching an average peak concentration of 32.72 ng/mL at 1.78 h. However, incomplete absorption was observed, with an absolute bioavailability of only 20.06% ± 10.84%. Additionally, bromhexine hydrochloride displayed wide distribution, with a steady-state distribution volume (VSS) of 22.55 ± 13.45 L/kg, and slow elimination, with a clearance (Cl) of 1.52 ± 0.38 L/h/kg. Furthermore, gender effects were assessed on the pharmacokinetics of bromhexine hydrochloride in broilers, revealing better absorption in male broilers compared to females. This disparity may be attributed to the faster blood flow and richer blood volume typically found in male broilers.

Comparison of gamithromycin residue depletion in yellow-feather and white-feather broilers after one single subcutaneous injection.

This study aimed to compare the residue depletion of gamithromycin in yellow-feather and white-feather broilers, using Sanhuang and Arbor Acres chickens as typical examples, respectively. Each breed (54 chickens) received a single subcutaneous dose of gamithromycin at 7.5 mg/kg bodyweight (BW). Tissues, including muscle, skin + fat, liver, kidney, and injection site, were collected at 6 h, 3, 5, 7, 10, 14, 21, 28, and 35 d postdrug administration. Gamithromycin concentrations in these tissues were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The kinetics of gamithromycin were analyzed in different tissues using a noncompartmental method in the Phoenix software. Differences were observed in gamithromycin concentrations and kinetic characteristics in both breeds of chickens, with higher residue concentrations and longer residue times found in yellow-feathered broilers. In Sanhuang broilers, the elimination rates of gamithromycin followed this order: injection site > muscle > liver > kidney > skin + fat. The corresponding elimination half-lives (t1/2λzs) in these samples were 1.22, 1.30, 1.71, 2.04, and 2.52 d, respectively. In contrast, in Arbor Acres broilers, a different order was noted: muscle > injection site > kidney > liver > skin + fat, with corresponding t1/2λzs of 1, 1.23, 1.88, 1.93, and 2.21 d, respectively. These differences may be related to variations in pigments in various tissues of chickens of the 2 breeds. However, further investigations are warranted to discern the underlying reasons.

Phase 2 study using low dose cytarabine for adult patients with newly diagnosed Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) lacks a standardized first-line therapy. This single-center, phase 2 prospective study (NCT04121819) enrolled 61 newly diagnosed adult LCH patients with multisystem or multifocal single system disease from October 2019 to June 2022. Subcutaneous cytarabine (100 mg/m2 for 5 days) was administered in 35-day cycles for 12 total cycles. The primary endpoint was event-free survival (EFS). The median age was 33 years (range 18-66). Twelve patients (19.7%) had liver involvement, of which 2 also had spleen involvement. Among 43 patients undergoing next-generation sequencing, BRAF alterations (44.2%) were most frequent, followed by TP53 (16.3%), MAP2K1 (14.0%) and IDH2 (11.6%). MAPK pathway alterations occurred in 28 patients (65.1%). The overall response rate was 93.4%, with 20 (32.7%) achieving complete response and 37 (60.7%) partial response. After a median 30 months follow-up, 21 (34.4%) relapsed without deaths. Estimated 3-year OS and EFS were 100.0% and 58.5%, respectively. Multivariate analysis identified ≥3 involved organs (P = 0.007; HR 3.937, 95% CI: 1.456-9.804) and baseline lung involvement (P = 0.028; HR 2.976, 95% CI: 1.126-7.874) as poor prognostic factors for EFS. The most common grade 3-4 toxicities were neutropenia (27.9%), thrombocytopenia (1.6%), and nausea (1.6%). In conclusion, cytarabine monotherapy is an effective and safe regimen for newly diagnosed adults, while baseline lung or ≥3 involved organs confers poor prognosis.

In vitro antibacterial activity of danofloxacin against Escherichia coli in Gushi chickens and its residue depletion following multiple oral administration.

This study aimed to investigate the in vitro antibacterial activity of danofloxacin against Escherichia coli isolated from Gushi chickens, as well as the tissue distribution and residue depletion of danofloxacin in Gushi chickens following multiple oral administration. A total of 42 clinical E. coli strains were isolated from the cloaca of locally farmed Gushi chickens between August and October 2023. Then the minimum inhibitory concentration (MIC) of danofloxacin against these isolates was determined by broth microdilution method. Additionally, 42 healthy Gushi chickens were randomly divided into 6 groups, and danofloxacin was orally administered at a dose of 5 mg/kg body weight (BW) for 3 consecutive days. Plasma, intestinal content, and tissue samples, including muscle, skin + fat, liver, kidney, lung, and intestine, were collected at 4, 12, 24, 48, 72, and 120 h after the last administration. Danofloxacin concentrations in all samples were determined using a high-performance liquid chromatography (HPLC) method. The average concentration vs. time data were then subjected to noncompartmental analysis using Phoenix software, and withdrawal periods for danofloxacin in Gushi chickens were further determined with WT1.4 software, setting a 95% confidence interval. Results indicated a notable inhibitory effect of danofloxacin on E. coli, with an MIC50 of 0.5 µg/mL. Additionally, danofloxacin exhibited widespread distribution in Gushi chickens, detectable in all collected samples. Among all tissues, the liver exhibited the highest concentration, followed by the intestine. Even on the fifth day postadministration, danofloxacin persisted in skin + fat, liver, and lung. The elimination half-lives (t1/2λzs) of danofloxacin varied across samples: skin + fat (47.87 h), lung (30.61 h), liver (22.07 h), plasma (16.05 h), muscle (12.53 h), intestine (9.83 h), and kidney (6.34 h). Considering residue depletion and the maximum residue limit (MRL) of danofloxacin in poultry set by Chinese regulatory authorities, withdrawal periods for the kidney, muscle, liver, and skin + fat were determined as 1.03, 1.38, 3.34, and 5.85 d, respectively, rounded to a final withdrawal time of 6 d.

Nickel doping of ferrous disulfide nanocubes exhibits enhanced oxidase-like activity for In vitro detection of total antioxidant capacity.

The development of nanomaterials that mimic oxidase-like activities has recently attracted an increasing amount of attention. Obtaining highly active and cost-effective oxidase mimics has posed a significant challenge in this area of research. In this study, we successfully synthesized nickel-doped ferrous disulfide nanocubes (Ni-FeS2) via a facile one-step method. Characterization by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed that Ni was predominantly distributed within the surface layer of the Ni-FeS2 nanocubes. The incorporation of nickel in density functional theory (DFT) calculations effectively reduced the d-band center of Fe, resulting in weakened adsorption to intermediates and thereby enhancing its catalytic efficiency. Moreover, we developed a novel approach based on Ni-FeS2 (the Ni-FeS2 method) for detecting reducing substances, which exhibited good sensitivity toward ascorbic acid (AA), glutathione (GSH), and cysteine (Cys). Remarkably, the established Ni-FeS2 method was successfully employed for in vitro assessment of total antioxidant capacity (TAC) in cellular and organ samples, thereby enabling discrimination between normal, senescent, and malignant cells as well as distinguishing among healthy liver tissue, cancerous liver tissue, and metastatic organs.

Depletion of tilmicosin residue in Gushi chickens following oral administration via drinking water.

This study aimed to examine the depletion of tilmicosin residues in Gushi chickens following the administration at a concentration of 75 mg/L in their drinking water for three consecutive days. Plasma, liver, kidney, lung, muscle, and skin + fat samples were collected from 6 chickens at 6 h, 1, 3, 5, and 7 days after the treatment. Tilmicosin concentrations in the samples were determined using a high-performance liquid chromatography (HPLC) method. The findings revealed that the highest tilmicosin residues were detected in the liver, followed by the kidney, lung, skin + fat, muscle, and plasma. Notably, at 7 days post-treatment, no drug residue was detected in all samples except for the liver and kidney. The non-compartmental model was employed to calculate relevant pharmacokinetic parameters. The elimination half-lives (t1/2λz ) of tilmicosin were as follows, ranked from long to short: skin + fat (45.42 h), liver (44.17 h), kidney (40.06 h), plasma (37.64 h), lung (31.39 h), and muscle (30.05 h). Considering the current residue depletion and the maximum residue limits (MRLs) set by Chinese regulatory authorities, the withdrawal times for tilmicosin were estimated as 18.91, 10.81, and 8.58 days in the kidney, liver, and skin + fat, respectively. A rounded-up value of 19 days was selected as the conclusive withdrawal time. Furthermore, based on the observed tilmicosin concentrations in plasma and lung, combined with previously reported minimum inhibitory concentration (MIC) values against Mycoplasma gallisepticum, the current dosing regimen was deemed adequate for treating Mycoplasma gallisepticum infections in Gushi chickens.

Effects of chitooligosaccharide on the in vitro antibacterial activity against avian Escherichia coli and the pharmacokinetics of florfenicol in healthy chickens.

This study investigates the combined effects of chitooligosaccharide (COS) and florfenicol (FLO) on the inhibition of Escherichia coli in vitro, as well as the pharmacokinetic interactions between these compounds in healthy chickens. The minimum inhibitory concentration (MIC) of COS and FLO alone and the fractional inhibitory concentration index (FICI) after combined treatment were determined using the broth microdilution method and checkerboard method, respectively. Additionally, we evaluated the pharmacokinetic interactions between the 2 types of COS and FLO in healthy chickens. Thirty chickens were randomly divided into 3 groups: Florfenicol group (30 mg/kg), COS J85 group (COS J85 20 mg/kg + florfenicol 30 mg/kg), COS H85 group (COS H85 20 mg/kg + florfenicol 30 mg/kg). Either FLO or COS was orally administered by gavage. The concentrations of FLO in chicken plasma were measured at different time points after the drug withdrawal using high-performance liquid chromatography (HPLC), and pharmacokinetic parameters were calculated by a compartmental method. The results showed that COS J85 and COS H85, when combined with FLO, had FICI values of 0.1875 to 0.75 and 0.3125 to 1, respectively, indicating good synergistic or additive effects against Escherichia coli. The pharmacokinetics of FLO alone and in combination with COS followed a 1-compartment model with first-order absorption and elimination. Furthermore, the pharmacokinetic analysis revealed that the elimination half-life (t1/2ke) of florfenicol was significantly increased in the COS H85 group compared to oral administration of florfenicol alone (P < 0.05). Other pharmacokinetic parameters did not show significant changes (P > 0.05), except between the 2 combined treatment groups, where statistical differences were observed for various parameters, excluding the area under the concentration-time curve from the time of dosing to infinity (AUC) and peak concentration (Cmax).

Clinical features, genomic profiling, and outcomes of adult patients with unifocal Langerhans cell histiocytosis.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare highly heterogeneous histiocytosis, which can be divided into single system and multiple system disease according to site of involvement. There is a paucity of studies examining unifocal LCH in adults in the molecular era. RESULTS: We retrospectively analysed records from 70 patients with unifocal LCH. The median age at diagnosis was 36 years (18-69). The most common organ involved was the bone (70.0%), followed by pituitary gland (7.1%). Target gene sequencing of lesion tissues was performed on 32 of the 70 patients. MAPK/PI3K pathway alterations were observed in 78.1% of the patients; the most common mutations included BRAFV600E (28.1%), MAP2K1 (18.8%) and PIK3CA (9.4%). After a median follow-up time of 39.4 months (0.7-211.8), 10 (14.3%) patients developed disease progression, of whom 4 had local recurrence, 2 progressed to single-system multifocal and 4 progressed to multiple system LCH. The 3-year progression-free survival (PFS) was 81.9%. Univariate analysis showed that age < 30 years at diagnosis was associated with worse 3-year PFS (52.2% vs. 97.0%, p = 0.005). The 3-year overall survival was 100%. CONCLUSIONS: In our large cohort of adults with unifocal LCH, we found that prognosis of unifocal LCH in adults was very good, and age < 30 years at diagnosis was associated with increased relapse risk.

Pharmacokinetics of Danofloxacin in Gushi Chickens after Single Oral and Intravenous Administration.

This study aimed to determine the pharmacokinetics of danofloxacin in Gushi chickens after a single oral (PO) and intravenous (IV) dose at 5 mg/kg body weight (BW). Thirty-two Gushi chickens, aged 20 weeks, were selected and divided into two groups at random, with each group consisting of 16 chickens, evenly distributed between males and females. Following danofloxacin administration, blood samples were taken at predetermined time intervals and the plasma was separated. The concentrations of danofloxacin in plasma were quantified by HPLC with a fluorescence detector. Then the concentrations versus time data were subjected to non-compartmental analysis (NCA) using Phoenix software (version: 8.1.0). After administering danofloxacin orally at a dose of 5 mg/kg BW to Gushi chickens, our results demonstrated that the peak concentration reached 0.53 µg/mL at 4 h. The half-life of absorption (t1/2ka) was determined to be 2.37 ± 1.60 h, and the bioavailability (F) was calculated as 40.12 ± 15.83%. For both oral and intravenous administration, the area under the concentration-time curve (AUC0-∞) was determined to be 4.72 ± 1.86 and 11.76 ± 3.25 h·µg/mL, respectively. The corresponding elimination half-life (t1/2λz) was measured as 11.24 ± 3.90 and 10.17 ± 3.72 h. Moreover, the mean residence time (MRT) was calculated as 10.20 ± 2.47 and 7.05 ± 1.97 h for these respective routes. Based on the calculated AUC/MIC ratio values, it can be inferred that the 5 mg/kg BW dosage of danofloxacin, whether administered orally or intravenously, is expected to effectively treat Escherichia coli and Pasteurella multocida infections in Gushi chickens.

Safety and efficacy of jaktinib (a novel JAK inhibitor) in patients with myelofibrosis who are intolerant to ruxolitinib: A single-arm, open-label, phase 2, multicenter study.

Although ruxolitinib improves splenomegaly and constitutional symptoms in patients with myelofibrosis (MF), a substantial proportion of patients discontinue ruxolitinib because of intolerance. This phase 2 trial investigated the safety and efficacy of jaktinib, a novel JAK inhibitor in patients with ruxolitinib-intolerant MF. The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) at week 24. The secondary endpoints included change of MF-related symptoms, anemic response, and safety profiles. Between December 18, 2019, and November 24, 2021, 51 patients were enrolled, 45 treated with jaktinib 100 mg bid (100 mg bid group) and six received non-100 mg bid doses (non-100 mg bid group). The SVR35 at week 24 in the 100 mg bid group was 43.2% (19/44, 95% CI 29.7%-57.8%). There were 41.9% (13/31) of transfusion-independent patients with hemoglobin (HGB) ≤100 g/L who had HGB elevation ≥20 g/L within 24 weeks. The proportion of patients with a ≥50% decrease in the total symptom score (TSS 50) at week 24 was 61.8% (21/34). The most commonly reported grade ≥3 treatment-emergent adverse events (TEAEs) in the 100 mg bid group were anemia 31.1%, thrombocytopenia 22.2%, and infectious pneumonia 17.8%. A total of 16 (35.6%) in the 100 mg bid group had serious adverse events, and 4 (8.9%) were considered possibly drug related. These results indicate jaktinib can provide a treatment option for patients with MF who are intolerant to ruxolitinib.

Population Pharmacokinetics of Difloxacin in Crucian Carp (Carassius auratus) after a Single Oral Administration.

This study aimed to investigate the population pharmacokinetics of difloxacin in crucian carp (Carassius auratus) orally provided a single dose of 20 mg/kg body weight (BW). To achieve this, fish were sampled at various intervals using a sparse sampling strategy, and plasma samples were analyzed using the high-performance liquid chromatography (HPLC) method. Subsequently, naïve average data were analyzed using a non-compartmental method, and a population model was developed based on the nonlinear mixed effects approach. The covariate of BW and the relationship between covariances were sequentially incorporated into the population model. However, it was found that only covariance and not BW affected the population parameters. Therefore, the covariance model was taken as the final population model, which revealed that the typical values of the absorption rate constant (tvKa), apparent volume of distribution per bioavailability (tvV), and clearance rate per bioavailability (tvCl) were 1.18 1/h, 14.18 L/kg, and 0.20 L/h/kg, respectively. Based on the calculated free AUC/MIC values, the current oral dose of difloxacin (20 mg/kg BW) cannot generate adequate plasma concentrations to inhibit pathogens with MIC values above 0.83 µg/mL. Further study should be carried out to collect the pathogens from crucian carp and determine the MIC data of difloxacin against them. Pharmacodynamic experiments must also be further carried out to determine the optimal therapeutic dose for the treatment of Aeromonas hydrophila infection.