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1.
J Vet Pharmacol Ther ; 47(4): 300-307, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38520083

ABSTRACT

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, Drug
2.
J Vet Pharmacol Ther ; 47(1): 54-59, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37715547

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/veterinary
3.
J Vet Pharmacol Ther ; 47(1): 48-53, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37381629

ABSTRACT

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/pharmacokinetics
4.
J Vet Pharmacol Ther ; 45(6): 501-507, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35717656

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 Water
5.
J Vet Pharmacol Ther ; 45(4): 352-357, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35582881

ABSTRACT

The present study evaluated the pharmacokinetic profiles of danofloxacin (DNX) in freshwater crocodiles (Crocodylus siamensis), following single intramuscular (i.m.) administrations at two different dosages of 6 and 12 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 168 h. DNX in the harvested crocodile plasma was extracted using liquid-liquid extraction and analyzed using a validated high-performance liquid chromatography method equipped with fluorescence detection. The pharmacokinetic analysis was performed using a non-compartmental approach. DNX in plasma was quantifiable from 5 min to 168 h after i.m. administration at the two dosages in freshwater crocodiles. The area under the curve (AUC) and maximum concentration (Cmax ) values increased in a dose-dependent fashion. Long elimination half-life (48.18 and 67.29 h) and low clearance (0.024 and 0.020 ml/g h) were obtained in the high- and low-dose groups, respectively. According to the pharmacokinetic-pharmacodynamic surrogate (AUC0-24h /MIC > 125), i.m. single administration of DNX at a dosage of 6 mg/kg b.w. is predicted to have antibacterial success for disease caused by bacteria with MIC < 0.04 µg/ml in the freshwater crocodile, C. siamensis.


Subject(s)
Alligators and Crocodiles , Animals , Area Under Curve , Fluoroquinolones/pharmacokinetics , Fresh Water , Half-Life , Injections, Intramuscular/veterinary
6.
J Vet Pharmacol Ther ; 45(4): 402-408, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35332549

ABSTRACT

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/pharmacokinetics
7.
J Vet Pharmacol Ther ; 45(2): 147-152, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34845734

ABSTRACT

Clarithromycin (CLA) is a new ß-lactamase-resistant macrolide antibiotic with potent activity against gram-positive and some gram-negative bacteria. To the authors' best knowledge, limited pharmacokinetic information to establish suitable therapeutic plans is available for freshwater crocodiles. To assess the prudent use of antibiotic in reptiles, this study was conducted to explore the pharmacokinetic characteristics of CLA in the freshwater crocodile, Crocodylus siamensis, following either single intravenous (i.v.) or intramuscular (i.m.) administration at a dosage of 2.5 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 168 h. CLA plasma samples were cleaned up using liquid-liquid extraction, and analysed by a validated liquid chromatography tandem-mass spectrometry (LC-MS/MS). CLA was quantifiable from 5 min to 72 h after i.v. administration, whereas it was detectable for 168 after i.m. administration at an identical dose rate. A non-compartmental model was used to fit the plasma concentration of CLA versus time curve for each crocodile. The t1/2λz value, similar for both routes (20 h), indicated that the overall rate of elimination of CLA in crocodiles is relatively slow. The average i.m. F% was complete. The protein plasma bound was found to be about 30%. CLA is a time-dependent antibiotic, and the T > MIC is the best PK/PD predictor for its efficacy. The CLA dosage of 2.5 mg/kg appeared to produce an appropriate value of the PK-PD surrogate that predicts antibacterial success for disease caused by susceptible bacteria.


Subject(s)
Alligators and Crocodiles , Clarithromycin , Animals , Chromatography, Liquid/veterinary , Clarithromycin/pharmacokinetics , Fresh Water , Tandem Mass Spectrometry/veterinary
8.
Toxins (Basel) ; 13(10)2021 10 13.
Article in English | MEDLINE | ID: mdl-34679017

ABSTRACT

Ergot alkaloids (EAs) are mycotoxins mainly produced by the fungus Claviceps purpurea. EAs are known to affect the nervous system and to be vasoconstrictors in humans and animals. This work presents recent advances in swine and dairy feeds regarding 11 major EAs, namely ergometrine, ergosine, ergotamine, ergocornine, ergocryptine, ergocristine, ergosinine, ergotaminine, ergocorninine, ergocryptinine, and ergocristinine. A reliable, sensitive, and accurate multiple mycotoxin method, based on extraction with a Mycosep 150 multifunctional column prior to analysis using UHPLC-MS/MS, was validated using samples of swine feed (100) and dairy feed (100) for the 11 targeted EAs. Based on the obtained validation results, this method showed good performance recovery and inter-day and intra-day precision that are in accordance with standard criteria to ensure reliable occurrence data on EA contaminants. More than 49% of the swine feed samples were contaminated with EAs, especially ergocryptine(-ine) (40%) and ergosine (-ine) and ergotamine (-ine) (37%). However, many of the 11 EAs were not detectable in any swine feed samples. In addition, there were contaminated (positive) dairy feed samples, especially for ergocryptine (-ine) (50%), ergosine (-ine) (48%), ergotamine (-ine), and ergocristine (-ine) (49%). The mycotoxin levels in the feed samples in this study almost complied with the European Union regulations.


Subject(s)
Animal Feed/analysis , Ergot Alkaloids/analysis , Animals , Cattle , Chromatography, High Pressure Liquid/methods , Food Contamination/analysis , Mycotoxins/analysis , Swine , Tandem Mass Spectrometry/methods
9.
J Vet Pharmacol Ther ; 44(4): 575-582, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33107624

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/veterinary
10.
Animals (Basel) ; 10(8)2020 Jul 27.
Article in English | MEDLINE | ID: mdl-32727082

ABSTRACT

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.

11.
J Vet Pharmacol Ther ; 43(6): 527-532, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32524632

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/blood
12.
J Vet Pharmacol Ther ; 43(4): 307-312, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32112576

ABSTRACT

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 Allocation
13.
J Vet Pharmacol Ther ; 43(1): 19-25, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31271466

ABSTRACT

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 , Male
14.
J Vet Pharmacol Ther ; 43(2): 141-146, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31353505

ABSTRACT

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 , Hemangioma
15.
J Vet Pharmacol Ther ; 43(2): 215-221, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31851387

ABSTRACT

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, Intravenous
16.
J Vet Pharmacol Ther ; 43(2): 135-140, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31705691

ABSTRACT

To the best of our knowledge, limited pharmacokinetic information to establish suitable therapeutic plans is available for Hawksbill turtles. Therefore, the present study aimed to assess the pharmacokinetic features of tolfenamic acid (TA) in Hawksbill turtles, Eretmochelys imbricata, after single intravenous (i.v.) and intramuscular (i.m.) administration at dosage 4 mg/kg body weight (b.w.). The study (parallel design) used 10 Hawksbill turtles randomly divided into equal groups. Blood samples were collected at assigned times up to 144 hr. The concentrations of TA in plasma were quantified by a validated liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS). The concentration of TA in the experimental turtles with respect to time was pharmacokinetically analyzed using a noncompartment model. The Cmax values of TA were 89.33 ± 6.99 µg/ml following i.m. administration. The elimination half-life values were 38.92 ± 6.31 hr and 41.09 ± 9.32 hr after i.v. and i.m. administration, respectively. The absolute i.m. bioavailability was 94.46%, and the average binding percentage of TA to plasma protein was 31.39%. TA demonstrated a long half-life and high bioavailability following i.m. administration. Therefore, the i.m. administration is recommended for use in clinical practice because it is both easier to perform and provides similar plasma concentrations to the i.v. administration. However, further studies are needed to determine the clinical efficacy of TA for treatment of inflammatory disease after single and multiple dosages.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Turtles/metabolism , ortho-Aminobenzoates/pharmacokinetics , Administration, Intravenous/veterinary , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/blood , Area Under Curve , Biological Availability , Chromatography, Liquid/veterinary , Endangered Species , Half-Life , Injections, Intramuscular/veterinary , Protein Binding , Random Allocation , Reproducibility of Results , Tandem Mass Spectrometry/veterinary , Thailand , ortho-Aminobenzoates/administration & dosage , ortho-Aminobenzoates/blood
17.
J Food Prot ; 82(6): 1007-1015, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31121103

ABSTRACT

HIGHLIGHTS: Contamination with multiple mycotoxins was found in rice and barley. BEA, DAS, ZEA, and aflatoxins were the mycotoxins most frequently found in samples. The assessed mycotoxin exposure does not represent a health risk for consumers.


Subject(s)
Food Contamination , Hordeum , Mycotoxins , Oryza , Food Contamination/analysis , Hordeum/chemistry , Hordeum/microbiology , Mycotoxins/analysis , Oryza/chemistry , Oryza/microbiology , Tandem Mass Spectrometry , Thailand
18.
Toxicol Rep ; 2: 351-356, 2015.
Article in English | MEDLINE | ID: mdl-28962368

ABSTRACT

Zearalenone (ZEA) is a secondary fungal metabolite produced mainly by a Fusarium graminearum. To clarify the toxicokinetics, and residues of ZEA and its major metabolites α-zearalenol (α-ZOL) and ß-zearalenol (ß-ZOL) in chickens, ZEA was then administered intravenously (iv) or orally (po) to broiler chickens at a dosage of 1.2 mg/kg body weight. The concentrations of ZEA, α-ZOL and ß-ZOL in the plasma and various tissues were quantified using LC-MS/MS. The plasma concentrations of ZEA were measurable up to 2 h after iv and po administration, and the concentrations of α-ZOL and ß-ZOL were detected up to 4 h after both types of administration. A two-compartment model was developed to describe the toxicokinetic of ZEA in broilers. The values of t1/2ß and Vd were 1.36 ± 0.29 h and 6.40 ± 0.89 l/kg, respectively. The absolute oral bioavailability was 29.66 ± 5.6%. ZEA, α-ZOL and ß-ZOL were measurable in the vital organs after po administration. These results suggest that ZEA is absorbed from the gastrointestinal tract and it has ability to penetrate into the various tissues of broiler chickens.

19.
J Vet Med Sci ; 76(12): 1549-53, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25649934

ABSTRACT

This study was conducted to evaluate the pharmacokinetic characteristics of vincristine and their correlation with its clinical effects in dogs with transmissible venereal tumor (TVT). Dogs with TVT were intravenously administered vincristine sulfate at a dose of 0.7 mg/m(2) of body surface area. Blood samples were collected starting from 5 min to 48 hr after drug administration. The plasma concentration of vincristine was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters of vincristine were characterized using a two-compartmental pharmacokinetic model. The volume of distribution, distribution half-life, elimination half-life and plasma clearance were 0.660 ± 0.210 l/kg, 21.5 ± 6.90 min, 47.6 ± 14.2 min and 0.010 ± 0.001 l/min/kg, respectively. Tumor regression was determined at weekly interval by a physical examination and histopathological analysis. In our study, three to eight administrations of vincristine at a dose of 0.7 mg/m(2) were able to induce a complete tumor regression without any evidence of gross lesion of disease. Therefore, this investigation provides the pharmacokinetic characteristics of vincristine in dogs with TVT, which may be used as an integration tool to gain a better understanding of the disposition properties of the drug and the correlation of these properties with the drug's clinical effects. In addition, we validated the LC-MS/MS method and found that it is suitable for the pharmacokinetic study of vincristine in dog plasma.


Subject(s)
Chromatography, Liquid/veterinary , Dog Diseases/drug therapy , Tandem Mass Spectrometry/veterinary , Venereal Tumors, Veterinary/drug therapy , Vincristine/pharmacokinetics , Administration, Intravenous , Animals , Chromatography, Liquid/methods , Dogs , Half-Life , Models, Biological , Tandem Mass Spectrometry/methods , Vincristine/administration & dosage , Vincristine/blood , Vincristine/therapeutic use
20.
J Food Prot ; 71(9): 1931-3, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18810882

ABSTRACT

A total of ninety samples in three kinds of wheat products (30 noodle, 30 bread, and 30 cereal samples) were collected from the supermarkets in Bangkok, Thailand, from February to April 2007. The occurrence of deoxynivalenol (DON) contamination in wheat products was investigated using high-performance liquid chromatography equipped with a UV light detector. The extraction method was performed using a multifunctional cleanup column. The limit of quantification was 0.10 microg x g(-1) from the range obtained in a linear calibration. The survey found almost 94% of the DON-contaminated samples below 1 microg x g(-1), which corresponds to the U.S. Food and Drug Administration advisory level. DON was detected in 18.9% (17 of 90) of all samples, in 6.67% (2 of 30) and 16.67% (5 of 30) of noodle and bread samples at levels from 0.17 to 0.35 and 0.14 to 1.13 microg x g(-1), respectively, while it was in 33.33% (10 of 30) of cereal samples at levels from 0.13 to 0.39 microg x g(-1). The results suggest that the exposure to DON from the consumption of wheat products, especially noodles, bread, and cereal, is at a very low risk level.


Subject(s)
Consumer Product Safety , Food Contamination/analysis , Fusarium/metabolism , Trichothecenes/isolation & purification , Triticum/chemistry , Chromatography, High Pressure Liquid/methods , Food Microbiology , Humans , Mycotoxins/analysis , Risk Assessment , Sensitivity and Specificity , Thailand , Trichothecenes/analysis
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