ABSTRACT
IMPORTANCE: Over the past decade, catfish farming has increased in Southeast Asia. However, there has been no existing for pharmacokinetic data in the hybrid catfish (Clarias macrocephalus x C. gariepinus). OBJECTIVE: This study was designed to evaluate the pharmacokinetic characteristics of oxytetracycline (OTC) in the hybrid catfish, following single intravascular (IV) or oral (PO) administration at a single dosage of 50 mg/kg body weight (BW). METHODS: In total, 140 catfish (each about 100-120 g BW) were divided into two groups (n = 70). Blood samples (0.6-0.8 mL) were collected from ventral caudal vein at pre-assigned times up to 144 h (sparse samples design). OTC plasma concentrations were analyzed using high-performance liquid chromatography-photodiode array detector. RESULTS: The pharmacokinetic parameter of OTC was evaluated using a non-compartment model. OTC plasma concentrations were detectable for up to 144 and 120 h after IV and PO, respectively. The elimination half-life value of OTC was long with slow clearance after IV administration in hybrid catfish. The average maximum concentration value of OTC was 2.72 µg/mL with a time at the maximum concentration of 8 h. The absolute PO bioavailability was low (2.47%). CONCLUSIONS AND RELEVANCE: These results showed that PO administration of OTC at a dosage of 50 mg/kg BW was unlikely to be effective for clinical use in catfish. The pharmacodynamic properties and clinical efficacy of OTC after multiple medicated feed are warranted.
Subject(s)
Catfishes , Oxytetracycline , Animals , Oxytetracycline/pharmacokinetics , Oxytetracycline/administration & dosage , Oxytetracycline/blood , Administration, Oral , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/blood , Injections, Intravenous/veterinary , Half-LifeABSTRACT
The pharmacokinetics of florfenicol (FFC) in green sea and hawksbill sea turtles were evaluated following intramuscular (i.m.) administration at two different dosages of 20 or 30 mg/kg body weight (b.w.). This study (longitudinal design) used 5 green sea and 5 hawksbill sea turtles for the two dosages. Blood samples were collected at assigned times up to 168 h. FFC plasma samples were analyzed using validated high-performance liquid chromatography equipped with diode array detection. The pharmacokinetic analysis was performed using a non-compartment approach. The FFC plasma concentrations increased with the dosage. The elimination half-life was similar between the treatment groups (range 19-25 h), as well as the plasma protein binding (range 18.59%-20.65%). According to the surrogate PK/PD parameter (T > MIC, 2 µg/mL), the 20 and 30 mg/kg dosing rates should be effective doses for susceptible bacterial infections in green sea and hawksbill sea turtles.
Subject(s)
Anti-Bacterial Agents , Thiamphenicol , Turtles , Animals , Turtles/blood , Turtles/metabolism , Thiamphenicol/analogs & derivatives , Thiamphenicol/pharmacokinetics , Thiamphenicol/administration & dosage , Thiamphenicol/blood , Injections, Intramuscular/veterinary , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/blood , Half-Life , Area Under Curve , Dose-Response Relationship, DrugABSTRACT
CMC is the most frequently diagnosed cancer and one of the leading causes of death in non-spayed female dogs. Exploring novel therapeutic agents is necessary to increase the survival rate of dogs with CMC. MPOBA is a BZOP derivative that has a significant anticancer effect in a human cell line. The main goal of this study was to investigate the anticancer properties of MPOBA against two CMC cell lines (REM134 and CMGT071020) using a 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, a wound healing assay, a transwell migration assay, an Annexin V-FITC apoptosis assay with a flow cytometry analysis, a mRNA expression analysis using quantitative real-time PCR (qRT-PCR), and an immunohistochemistry (IHC). According to the accumulated studies, MPOBA caused significant concentration- and time-dependent reductions in cell proliferation and cell migration and induced apoptosis in both CMC cell lines. In gene expression analysis, nine canine genes, including TP53, BCL-2, BAX, epidermal growth factor receptor (EGFR), snail transcription factor (SNAIL), snail-related zinc-finger transcription factor (SLUG), TWIST, E-cadherin, and N-cadherin, were investigated. The mRNA expression results revealed that MPOBA induced upregulation of TP53 and overexpression of the pro-apoptotic gene BAX, together with an inhibition of BCL-2. Moreover, MPOBA also suppressed the mRNA expression levels of SNAIL, EGFR, and N-cadherin and induced upregulation of E-cadherin, crucial genes related to the epithelial-to-mesenchymal transition (EMT). However, there was no significant difference in the IHC results of the expression patterns of vimentin (VT) and cytokeratin (CK) between MPOBA-treated and control CMC cells. In conclusion, the results of the present study suggested that MPOBA exhibited significant anticancer activity by inducing apoptosis in both CMCs via upregulation of TP53 and BAX and downregulation of BCL-2 relative mRNA expression. MPOBA may prove to be a potential candidate drug to be further investigated as a therapeutic agent for CMC.
ABSTRACT
The pharmacokinetics were described of meloxicam (MLX) in green sea turtles (Chelonia mydas), following a single intravenous (i.v.) and intramuscular (i.m.) administrations at one of two dosages of 0.1 or 0.2 mg/kg body weight (b.w.). The sample of 20 green sea turtles was divided into four groups (n = 5) using a randomization procedure according to a parallel study design. Blood samples were collected at pre-assigned times up to 168 h. MLX in the plasma was cleaned-up and quantified using a validated high-performance liquid chromatography method with UV detection. The concentration of MLX in the experimental green sea turtles with respect to time was pharmacokinetically analyzed using a non-compartment model. MLX plasma concentrations were quantifiable for up to 72 and 120 h after i.v. at dosages of 0.1 and 0.2 mg/kg b.w., respectively, whereas it was measurable for up to 168 h after i.m. administration at both dosages. The long elimination half-life value of MLX (28 h) obtained in green sea turtles after i.v. administration was consistent with the quite slow clearance rate for both dosages. The average maximum concentration (Cmax ) values of MLX were 1.05 µg/mL and 4.26 µg/mL at dosages of 0.1 and 0.2 mg/kg b.w., respectively, with their elimination half-life values being 37.26 h and 30.64 h, respectively, after i.m. administrations. The absolute i.m. bioavailability was approximately 110%. These results suggested that i.m. administration of MLX at a dosage of 0.2 mg/kg b.w. was likely to be effective for clinical use in green sea turtles (Chelonia mydas). However, further studies are needed to determine the pharmacodynamic properties and clinical efficacy of MLX for the treatment of inflammatory disease after single and multiple dosages.
Subject(s)
Turtles , Animals , Meloxicam , Half-Life , Injections, Intramuscular/veterinary , Administration, Intravenous/veterinaryABSTRACT
To date, the pharmacokinetics of fluoroquinolones in estuarine crocodiles (Crocodylus porosus) have been reported for enrofloxacin but not for marbofloxacin (MBF), which is a broad-spectrum antibiotic used only in veterinary medicine. This study investigated the pharmacokinetics of MBF after intramuscular administration at two difference dosages (2 and 4 mg/kg body weight) in estuarine crocodiles and estimated pharmacokinetic/pharmacodynamic (PK/PD) surrogate parameters for the optimization of dosage regimens. Ten treated estuarine crocodiles were divided into two groups (n = 5) using a randomization procedure according to a parallel study design. Blood samples were collected at assigned times up to 168 h. MBF plasma samples were cleaned up using liquid-liquid extraction and analyzed using a validated high-performance liquid chromatography method with fluorescence detection. A non-compartment approach was used to fit the plasma concentration of MBF vs time curve for each crocodile. The plasma concentrations of MBF were quantifiable for up to 168 h in both groups. The elimination half-life values of MBF were long (33.99 and 39.28 h for 2 and 4 mg/kg, respectively) with no significant differences between the groups. The average plasma protein binding of MBF was 30.85%. According to the surrogated PK/PD parameter (AUC0-24 -to-MIC ratio >100-125), the 2 and 4 mg/kg dosing rates should be effective for bacteria with MIC values lower than 0.125 µg/mL and 0.35 µg/mL, respectively.
Subject(s)
Alligators and Crocodiles , Animals , Area Under Curve , Injections, Intramuscular/veterinary , Fluoroquinolones/pharmacokineticsABSTRACT
Aflatoxin B1 (AFB1) is the most potent naturally occurring carcinogen for humans and animals produced by the common fungus Aspergillus flavus (A. flavus). Aflatoxin (AF) contamination in commodities is a global concern related to the safety of food and feed, and it also impacts the agricultural economy. In this study, we investigated the AFB1-inhibiting activity of a new benzaldehyde derivative, 2-[(2-methylpyridin-3-yl)oxy]benzaldehyde (MPOBA), on A. flavus. It was found that MPOBA inhibited the production of AFB1 by A. flavus, with an IC50 value of 0.55 mM. Moreover, the inhibition of conidiation was also observed at the same concentration. The addition of MPOBA resulted in decreased transcript levels of the aflR gene, which encodes a key regulatory protein for the biosynthesis of AF, and also decreased transcript levels of the global regulator genes veA and laeA. These results suggested that MPOBA has an effect on the regulatory mechanism of the development and differentiation of conidia, leading to the inhibition of AFB1 production. In addition, the cytotoxicity study showed that MPOBA had a very low cytotoxic effect on the Madin-Darby canine kidney (MDCK) cell line. Therefore, MPOBA may be a potential compound for developing practically effective agents to control AF contamination.
ABSTRACT
The study evaluated the pharmacokinetic features of azithromycin (AZM) in 15 freshwater crocodiles (Crocodylus siamensis) in Thailand. The crocodiles were administered a single intramuscular (i.m.) injection of AZM at three different dosages of 2.5, 5, and 10 mg/kg body weight (b.w.). Blood samples were collected at pre-assigned times up to 168 h. The plasma concentrations of AZM were measured using a validated liquid chromatography-tandem mass spectrometry method. The plasma concentration of AZM were quantifiable for up to 168 h after i.m. administration at the three different dosages. A non-compartmental model was used to fit the plasma concentration of AZM versus the time curve for each crocodile. The elimination half-life values of AZM were 33.70, 38.11, and 34.80 h following i.m. injection after dosages of 2.5, 5, and 10 mg/kg b.w., respectively. There were no significant differences among groups. The results indicated that the overall rate of elimination of AZM in freshwater crocodiles was relatively slow. The maximum concentration and area under the curve from zero to the last values of AZM increased in a dose-dependent fashion. The average binding percentage of AZM to plasma protein was 48.66%. Based on the pharmacokinetic data, the susceptibility break-point and the surrogate PK-PD index (T > MIC), the intramuscular administration of AZM at a dose of 10 mg/kg b.w. might be appropriate for the treatment of susceptible bacterial infections (MIC < 4 µg/ml) in freshwater crocodiles.
Subject(s)
Alligators and Crocodiles , Azithromycin , Animals , Azithromycin/pharmacokinetics , Azithromycin/therapeutic use , Alligators and Crocodiles/metabolism , Anti-Bacterial Agents , Chromatography, Liquid/veterinary , Fresh WaterABSTRACT
To date, the number of green sea and hawksbill sea turtles is in decline due to environmental, anthropogenic, and pathological factors. The present study described the pharmacokinetic characteristics of danofloxacin (DNX) in green sea and hawksbill sea turtles, following single intravenous (i.v.) and intramuscular (i.m.) administrations at single dosages of 6 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 168 h. DNX in the harvested plasma was cleaned up using liquid-liquid extraction and analyzed using a validated high-performance liquid chromatography method with fluorescence detection. The pharmacokinetic analysis was performed using a non-compartmental approach. DNX was quantifiable from 5 min to 168 h after i.v. and i.m. administrations at an identical dosage in both turtle types. No statistical differences were found in the pharmacokinetic parameters between green sea and hawksbill sea turtles. The long elimination half-life value of DNX obtained in green sea (35 h) and hawksbill sea (30.21 h) turtles was consistent with the quite large volume of distribution and the slow clearance rate. The high values of absolute bioavailability (87%-94%) should be advantageous for clinical use of DNX in sea turtles. According to the pharmacokinetic-pharmacodynamic surrogate (AUC0-24 /MIC > 125), DNX is predicted to have antibacterial success for disease caused by bacteria with MIC < 0.04 µg/ml.
Subject(s)
Turtles , Administration, Intravenous/veterinary , Animals , Anti-Bacterial Agents/pharmacokinetics , Fluoroquinolones/pharmacokineticsABSTRACT
BACKGROUND: The anti-cancer effects of Gynura procumbens leaves extract (GPE) have been reported in various human cancers. However, the anti-cancer effects and molecular mechanisms of this extract on canine mammary cancer (CMC) have not yet been elucidated. OBJECTIVES: The main goal of this study was to investigate the anti-cancer properties of GPE against two CMC cell lines (CHMp-13a and CHMp-5b). METHODS: The GP leaves were extracted with 80% ethanol. Anti-cancer potentials of GPE on CHMp-13a and CHMp-5b cancer cell lines using dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide (MTT), wound healing, transwell migration, and caspase 3/7 activity assays were evaluated. The mRNA expression levels of two oncogenes: epidermal growth factor receptor (EGFR) and twist family bHLH transcription factor 1 (TWIST) and one tumour suppressor gene: phosphatase and tensin homolog (PTEN) in these cell lines were determined by quantitative real-time PCR (qRT-PCR). In addition, The EGFR and PTEN protein levels as well as protein kinase B (AKT) and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation levels expression were also evaluated by western blot analysis. RESULTS: The results showed that GPE caused a significant concentration- and time-dependent reduction in cell proliferation of both CHMp-13a and CHMp-5b cells, detected by MTT assays. This extract also significantly suppressed cancer cell migration in both cell lines, tested by wound healing and transwell migration assays. Additionally, the increase in caspase 3/7 activity observed in both CMC cell treated with GPE suggests that GPE induced caspase 3/7 dependent apoptosis. Moreover, GPE significantly decreased EGFR mRNA and protein expression levels compared to control in both cell lines in a dose-dependent manner. CONCLUSION: These findings emphasized that GPE has an in vitro anti-cancer activity against CMC by inhibiting EGFR signalling pathway. Thus, GPE may serve as an alternative therapy in CMC with high EGFR expression.
Subject(s)
Breast Neoplasms , Dog Diseases , Animals , Breast Neoplasms/veterinary , Cell Line , Cell Proliferation , Dogs , Female , Plant Extracts/pharmacology , Plant LeavesABSTRACT
A significant impact of marine pollution is the contamination of seafood which has raised concerns due to its potential human health risks. This current study investigated seasonal bioaccumulation of 9 heavy metals (Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, and Zn) in 14 commercially important seafood species, including 4 fish, 5 molluscs, and 5 crustacean species. Samples were collected from Pattani Bay, Pattani province, Thailand, during the dry (July 2020) and wet (February 2021) seasons. The edible samples were analyzed for heavy metal concentrations using a flame atomic absorption spectrophotometer. The bioaccumulation trend of heavy metals decreased in the sequence of molluscs > crustaceans > fish. The possible human health risks associated with heavy metal-contaminated seafood consumption were assessed. The parameters investigated for non-carcinogenic and carcinogenic were target hazard quotient (THQ), total hazard index (HI), and target cancer risk (TR). The average ranges of THQs (7.79 × 10−8−8.97 × 10−3), HIs (4.30 × 10−5−1.55 × 10−2), and TRs (2.70 × 10−9−1.34 × 10−5) were observed in the studied seafood species. The results revealed no non-carcinogenic and carcinogenic health risks from consuming these 14 kinds of seafood.
ABSTRACT
The present study aimed to assess the pharmacokinetic features of enrofloxacin (ENR) and its major metabolite, ciprofloxacin (CIP) in green sea turtles (Chelonia mydas) after single intravenous (i.v.) and intramuscular (i.m.) administration at two dosages of 5 and 7.5 mg/kg body weight (b.w.). The study used 10 animals randomly divided into equal groups. Blood samples were collected at assigned times up to 168 hr. The concentrations of ENR and CIP in turtle plasma were quantified by a validated high-performance liquid chromatography equipped with fluorescence detector (HPLC-FLD). The concentration of ENR in the experimental turtles with respect to time was pharmacokinetically analyzed using a noncompartment model. The concentrations of ENR in the plasma were quantified up to 144 hr after i.v. and i.m. administrations at dosages of 5 and 7.5 mg/kg b.w., whereas CIP was quantified up to 96 and 144 hr, respectively. The elimination half-life values of ENR were 38.7 and 50.4 hr at dose rates of 5 and 7.5 mg/kg b.w. after i.v. administration, whereas CIP was 33.6 and 22.6 hr, respectively. The maximum concentration (Cmax ) values of ENR were 2.07 and 2.59 µg/ml at dose rates of 5 and 7.5 mg/kg b.w., respectively. The value of area under the curve from 0 to 24 hr (AUC0-24 )/minimum inhibitory concentration (MIC) ratio of ENR was >125 for bacteria with MIC of 0.12 and 0.13 µg/ml after the administration of 5 mg/kg by i.m. and i.v. administration, respectively. Based on the pharmacokinetic data, susceptibility break-point and pharmacokinetic (PK)/pharmacodynamic (PD) indices, i.m. single administration of ENR at a dosage of 5 mg/kg b.w. might be clinically appropriate for treatment of susceptible bacteria in green sea turtles (Chelonia mydas).
Subject(s)
Ciprofloxacin , Turtles , Animals , Anti-Bacterial Agents , Area Under Curve , Enrofloxacin , Fluoroquinolones , Microbial Sensitivity Tests/veterinaryABSTRACT
To date, the necessary pharmacokinetic information has been limited to establish suitable therapeutic plans for freshwater crocodiles. Therefore, this study was conducted to evaluate the pharmacokinetic profile of the oxytetracycline long-acting formulation (OTC-LA) in the freshwater crocodile, Crocodylus siamensis, following a single intramuscular (i.m.) administration at three different dosages of 5, 10 and 20 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 216 h after i.m. administration at the three different dosages. The plasma concentrations of OTC were measured using a validated liquid chromatography tandem-mass spectrometry (LC-MS/MS) method. The Cmax (± SD) values of OTC were 2.15 ± 0.51 µg/mL, 7.68 ± 1.08 µg/mL and 17.08 ± 2.09 µg/mL at doses of 5, 10 and 20 mg/kg b.w., respectively. The elimination half-life values were 33.59 ± 2.51 h, 38.42 ± 5.47 h and 38.04 ± 1.98 h at dosages of 5, 10 and 20 mg/kg b.w., respectively. Based on the pharmacokinetic data, the pharmacokinetic/pharmacodynamic (PK/PD) index, the susceptibility break-point and plasma protein binding, a dosage once every two weeks of 10 mg/kg b.w. OTC intramuscularly might be suitable for initiating the treatment of susceptible bacterial infections in freshwater crocodiles. However, further PK/PD studies are warranted to confirm whether the dose rates used in this study can produce longer-term antimicrobial success for diseases caused by susceptible bacteria in freshwater crocodiles.
ABSTRACT
The present study aimed to evaluate the pharmacokinetic features of tolfenamic acid (TA) in green sea turtles, Chelonia mydas. Green sea turtles were administered single either intravenous (i.v.) or intramuscular (i.m.) injection of TA, at a dose of 4 mg/kg body weight (b.w.). Blood samples were collected at preassigned times up to 168 hr. The plasma concentrations of TA were measured using a validated liquid chromatography tandem mass spectrometry method. Tolfenamic acid plasma concentrations were quantifiable for up to 168 hr after i.v. and i.m. administration. The concentration of TA in the experimental green sea turtles with respect to time was pharmacokinetically analyzed using a noncompartment model. The Cmax values of TA were 55.01 ± 8.34 µg/ml following i.m. administration. The elimination half-life values were 32.76 ± 4.68 hr and 53.69 ± 3.38 hr after i.v. and i.m. administration, respectively. The absolute i.m. bioavailability was 72.02 ± 10.23%, and the average binding percentage of TA to plasma protein was 19.43 ± 6.75%. Based on the pharmacokinetic data, the i.m. administration of TA at a dosage of 4 mg/kg b.w. might be sufficient to produce a long-lasting anti-inflammatory effect (7 days) for green sea turtles. However, further studies are needed to determine the clinical efficacy of TA for treatment of inflammatory disease after single and multiple dosages.
Subject(s)
Analgesics/pharmacokinetics , Turtles/blood , ortho-Aminobenzoates/pharmacokinetics , Analgesics/administration & dosage , Analgesics/blood , Animals , Area Under Curve , Half-Life , Injections, Intramuscular , Injections, Intravenous , ortho-Aminobenzoates/administration & dosage , ortho-Aminobenzoates/bloodABSTRACT
The aim of the present study was to elucidate the pharmacokinetic profiles of amoxicillin trihydrate (AMX) in Siamese freshwater crocodiles (Crocodylus siamensis). Crocodiles were administered a single intramuscular injection of AMX, at a dose of either 5 or 10 mg/kg body weight (b.w.). Blood samples were collected at preassigned times up to 120 hr. The plasma concentrations of AMX were measured using a validated liquid chromatography tandem-mass spectrometry method. AMX plasma concentrations were quantifiable for up to 72 hr (5 mg/kg b.w.) and 96 hr (10 mg/kg b.w.). The elimination half-life (t1/2λ z ) of AMX following dosing at 5 mg/kg b.w. (8.72 ± 0.61 hr) was almost identical to that following administration at 10 mg/kg b.w (8.98 ± 1.13 hr). The maximum concentration and area under the curve from zero to the last values of AMX increased in a dose-dependent fashion. The average binding percentage of AMX to plasma protein was 21.24%. Based on the pharmacokinetic data, susceptibility break point, and the surrogate PK-PD index (T > MIC, 0.25 µg/ml), intramuscular administration of AMX at dose of 5 mg/kg b.w. every 4 days might be appropriate for the treatment of susceptible bacterial infections in freshwater crocodiles.
Subject(s)
Alligators and Crocodiles/metabolism , Amoxicillin/pharmacokinetics , Anti-Bacterial Agents/pharmacokinetics , Alligators and Crocodiles/blood , Amoxicillin/administration & dosage , Amoxicillin/blood , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/blood , Area Under Curve , Drug Administration Schedule , Fresh Water , Half-Life , Injections, Intramuscular/veterinary , Male , Random AllocationABSTRACT
Limited pharmacokinetic information to establish suitable therapeutic plans is available for green sea turtles. Therefore, the present study was conducted to evaluate the pharmacokinetic characteristics of marbofloxacin (MBF) in the green sea turtle, Chelonia mydas, following single intravenous (i.v.) or intramuscular (i.m.) administration at two dosages of 2 and 4 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 168 hr. MBF in plasma was extracted using liquid-liquid extraction and analyzed by a validated high-performance liquid chromatography (HPLC). MBF was quantifiable from 15 min to 96 hr after i.v. and i.m. administrations at two dose rates. A noncompartmental model was used to fit the plasma concentration of MBF versus time curve for each green sea turtle. The t1/2λz value, similar for both the dosages (22-28 hr), indicated that the overall rate of elimination of MBF in green sea turtles is relatively slow. The average i.m. F% ranged 88%-103%. MBF is a concentration-dependent drug and the AUC/MIC ratio is the best PK/PD predictor for its efficacy. The MBF dosage of 4 mg/kg appeared to produce an appropriate value of the PK-PD surrogate that predicts antibacterial success for disease caused by susceptible bacteria. In contrast, i.m. administration of MBF at a dosage of 2 mg/kg b.w. was not found to produce a suitable PK-PD surrogate index. However, further studies of multiple doses and plasma binding proteins are warranted to confirm an appropriate dosage regimen.
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Fluoroquinolones/pharmacokinetics , Turtles/blood , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/blood , Area Under Curve , Dose-Response Relationship, Drug , Fluoroquinolones/administration & dosage , Fluoroquinolones/blood , Half-Life , Injections, Intramuscular , Injections, IntravenousABSTRACT
One of the major obstacles to the successful treatment of infectious disease in freshwater crocodile species is incorrect dosing of antibiotics. There are few reports on pharmacokinetics and dosage regimens of antimicrobial drugs in crocodiles. The purpose of the present study was to clarify the pharmacokinetic characteristics of ceftriaxone (CEF) in Siamese freshwater crocodiles (Crocodylus siamensis). Freshwater crocodiles, Crocodylus siamensis, in breeding farms were treated with a single intramuscular administration of CEF at two dosages, 12.5 and 25 mg/kg body weight (b.w.). Blood samples were collected at preassigned times up to 168 hr. The plasma concentrations of CEF were measured by a validated method through liquid chromatography tandem-mass spectrometry. CEF plasma concentrations were quantified up to 72 and 96 hr after low- and high-dose administration, respectively. The Cmax values of CEF were 24.61 ± 5.15 µg/ml and 26.39 ± 2.81 µg/ml at dosages of 12.5 and 25 mg/kg b.w., respectively. The AUClast values increased in a dose-dependent fashion. The half-life values were not statistically different between the groups (around 20 hr). The average binding percentage of CEF to plasma protein was 53.78 ± 2.11%. Based on the pharmacokinetic data, susceptibility break-point and the surrogate PK-PD index (T > MIC, 0.2 µg/ml), i.m. administration of CEF at a dose of 12.5 mg/kg b.w. might be appropriate for initiating treatment of susceptible bacterial infections in freshwater crocodiles.
Subject(s)
Alligators and Crocodiles/blood , Anti-Bacterial Agents/pharmacokinetics , Ceftriaxone/pharmacokinetics , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/blood , Area Under Curve , Ceftriaxone/administration & dosage , Ceftriaxone/blood , Dose-Response Relationship, Drug , Half-Life , HemangiomaABSTRACT
To the best of the authors' knowledge, pharmacokinetic information to establish suitable therapeutic plans for freshwater crocodiles is limited. Therefore, the purpose of this study was to clarify the pharmacokinetic characteristics of enrofloxacin (ENR) in freshwater crocodiles, Crocodylus siamensis, following single intravenous and intramuscular administration at a dosage of 5 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 168 hr. The plasma concentrations of ENR and its metabolite ciprofloxacin (CIP) were measured by liquid chromatography tandem-mass spectrometry. The concentrations of ENR and CIP in the plasma were quantified up to 144 hr after both the administrations. The half-life was long (43-44 hr) and similar after both administrations. The absolute i.m. bioavailability was 82.65% and the binding percentage of ENR to plasma protein ranged from 9% to 18% with an average of 10.6%. Percentage of CIP (plasma concentrations) was 15.9% and 19.9% after i.v. and i.m. administration, respectively. Based on the pharmacokinetic data, susceptibility break point and PK-PD indexes, i.m. single administration of ENR at a dosage of 5 mg/kg b.w. might be appropriate for treatment of susceptible bacteria (MIC > 1 µg/mL) in freshwater crocodiles, C. siamensis.
Subject(s)
Alligators and Crocodiles , Anti-Bacterial Agents/pharmacokinetics , Ciprofloxacin/metabolism , Ciprofloxacin/pharmacokinetics , Enrofloxacin/pharmacokinetics , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/blood , Anti-Bacterial Agents/metabolism , Area Under Curve , Ciprofloxacin/administration & dosage , Enrofloxacin/administration & dosage , Half-Life , Injections, Intramuscular , Injections, Intravenous , MaleABSTRACT
Eight duck farms and a local market in Suphanburi province, Thailand adjacent to paddy fields were selected for this study. The concentrations of endosulfan isomers (α- and ß-endosulfan) and endosulfan sulfate in environmental matrices (water, soil, feed) and duck eggs were determined. Human health risk via the contaminated egg consumption was also evaluated. Analysis of environmental matrices found both endosulfan isomers (α- and ß-endosulfan) and endosulfan sulfate in most samples. Endosulfan sulfate was predominantly found in all matrices followed by ß- and α-endosulfan, respectively. The total endosulfan concentrations were in the following order: feed > soil > water. However, the levels of endosulfan detected were lower than the regulatory maximum residue limit of endosulfan, except in water (>0.200 ng mL(-1)). Endosulfan sulfate in duck egg samples was also predominantly detected in both yolk and albumin. The average total endosulfan residues (∑endosulfan) in yolk (6.73 ng g(-1)) were higher than in albumin (4.78 ng g(-1)). According to principle component analysis, we found that paddy soil surrounding the duck farms is the suspected source of endosulfan contamination in husbandry water which subsequently contaminates duck eggs. The estimated daily intakes (EDIs) of these endosulfan-contaminated eggs were well below the acceptable daily intake (ADI) for endosulfan (6 µg kg(-1) day(-1)). However, the consumption of this contaminated duck eggs should be of concerns in regard to chronic exposure. Therefore, the better environmental managements to reduce endosulfan residues can play a crucial role for decreasing human health risk.
Subject(s)
Ducks , Eggs/analysis , Endosulfan/analysis , Environmental Exposure/analysis , Food Contamination/analysis , Insecticides/analysis , Animals , Environmental Exposure/statistics & numerical data , Environmental Monitoring , Food Contamination/statistics & numerical data , Humans , Risk , Soil/chemistry , ThailandABSTRACT
Antibiotic beads have become popular for the treatment of local bacterial infections. The preparation of antibiotic beads from commercial pharmaceutical antibiotics is a convenient method in clinic. The elution characteristics of cefazolin from polymethylmethacrylate (PMMA) (SmartSet HV, Depuy I and Cemfix 3) beads and calcium sulfate beads were studied. Commercial cefazolin formulation was incorporated in PMMA or calcium sulfate at 1 g cefazolin/10 g of matrix substances to form beads. The concentrations of eluted cefazolin during 15 days were greater than MIC for Staphylococcus aureus (ATCC 25923). The eluted cefazolin concentrations were in the range of 3.6 ± 1.2 to 4.6 ± 0.4 mg for PMMA beads and 15.4 ± 1.7 mg for calcium sulfate beads. The accumulated eluted cefazolin from PMMA beads and calcium sulfate beads for 15 days were 34.41 ± 3.93 to 38.67 ± 3.04% and 95.94 ± 3.93%, respectively. The various storage conditions; at room temperature or 4°C, with or without light-protection, for 6 months had little effects on the amounts of eluted cefazolin. The results showed both in-housed cefazolin-PMMA beads and cefazolin-calcium sulfate beads could be the effective tools for the treatment of local bacterial infections.