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1.
J Vet Pharmacol Ther ; 43(5): 435-439, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32743801

RESUMO

The objective of this study was to determine the pharmacokinetics of tolfenamic acid (TA) following intravenous (IV) administration at doses of 2 and 4 mg/kg in goats. In this study, six healthy goats were used. TA was administered intravenously to each goat at 2 and 4 mg/kg doses in a cross-over pharmacokinetic design with a 15-day washout period. Plasma concentrations of TA were analyzed using the high performance liquid chromatography with ultraviolet detector, and pharmacokinetic parameters were assigned by noncompartmental analysis. Following IV administration at dose of 2 mg/kg, area under the concentration-time curve (AUC0-∞ ), elimination half-life (t1/2ʎz ), total clearance (ClT ) and volume of distribution at steady state (Vdss ) were 6.64 ± 0.81 hr* µg/ml, 1.57 ± 0.14 hr, 0.30 ± 0.04 L h-1  kg-1 and 0.40 ± 0.05 L/kg, respectively. After the administration of TA at a dose of 4 mg/kg showed prolonged t1/2ʎz , increased dose-normalized AUC0-∞ , and decreased ClT . In goats, TA at 4 mg/kg dose can be administered wider dose intervals compared to the 2 mg/kg dose. However, further studies are needed to determine the effect of different doses on the clinical efficacy of TA in goats.

2.
J Vet Pharmacol Ther ; 43(5): 440-447, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32815194

RESUMO

The pharmacokinetics of cefquinome (2 mg/kg every 24 hr for 5 days) was determined following intramuscular administration alone and co-administration with ketoprofen (3 mg/kg every 24 hr for 5 days) in goats. Six goats were used for the study. In the study, the crossover pharmacokinetics design with 20-day washout period was performed in two periods. Plasma concentrations of cefquinome were assayed using high-performance liquid chromatography by ultraviolet detection. The mean terminal elimination half-life (t1/2ʎz ), area under the concentration-time curve (AUC0-24 ), peak concentration (Cmax ), apparent volume of distribution (Vdarea /F), and total body clearance (CL/F) of cefquinome after the administration alone were 4.85 hr, 11.06 hr*µg/ml, 2.37 µg/mL, 1.23 L/kg, and 0.17 L/h/kg after the first dose, and 5.88 hr, 17.01 hr*µg/mL, 3.04 µg/mL, 0.95 L/kg, and 0.11 L/h/kg after the last dose. Ketoprofen significantly prolonged t1/2ʎz of cefquinome, increased AUC0-24 and Cmax , and decreased Vdarea /F and CL/F. Cefquinome exhibited low accumulation after the administration alone and in combination with ketoprofen. These results indicated that ketoprofen prolonged the elimination of cefquinome in goats. The 24-hr dosing intervals at 2 mg/kg dose of cefquinome, which co-administered with ketoprofen, may maintain T> minimum inhibitory concentration (MIC) values above 40% in the treatment of infections caused by susceptible pathogens with the MIC value of ≤0.75 µg/ml in goats with an inflammatory condition.

3.
Acta Vet Hung ; 68(1): 65-70, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32384070

RESUMO

The pharmacokinetics of levofloxacin (4 mg/kg), administered both alone and in combination with tolfenamic acid (2 mg/kg) and flunixin meglumine (2.2 mg/kg), was established after intravenous administration in sheep. Plasma levofloxacin concentrations were assayed by high-performance liquid chromatography and analysed according to the two-compartment open model. Following the administration of levofloxacin alone, the mean distribution half-life, elimination half-life, total clearance, volume of distribution at steady state and area under the plasma concentration-time curve were 0.20 h, 1.82 h, 0.39 L/h/kg, 0.96 L/kg and 10.40 h × µg/mL, respectively. Tolfenamic acid and flunixin meglumine caused a slow elimination and increased plasma concentrations of levofloxacin in combination administration. Levofloxacin, with an alteration in the dosage regimen, can be used effectively with tolfenamic acid and flunixin meglumine for the therapy of infections and inflammatory conditions in sheep.

4.
J Vet Pharmacol Ther ; 43(5): 429-434, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32420638

RESUMO

The aim of this study was to determine the changes in the pharmacokinetics of meloxicam in goat kids who were castrated following the administration of xylazine. Six goat kids were used for the study. The study was performed in two periods according to a longitudinal study, with a 15-day washout period between periods. In the first period (Control group), 1 mg/kg meloxicam was administered by i.v. route to kids. In the second period (Castration group), the kids were sedated with 0.3 mg/kg xylazine and castration was performed following meloxicam administration. Plasma meloxicam concentration was analyzed using HPLC-UV, and pharmacokinetic parameters were calculated by noncompartmental model. In the control group following the administration of meloxicam, mean elimination half-life (t1/2 ʎz ), area under the concentration-time curve (AUC0-∞ ), total body clearance (ClT ), and volume of distribution at steady-state (Vdss ) were 13.50 ± 0.62 hr, 41.10 ± 2.86 hr µg/ml, 24.43 ± 1.75 ml hr-1  kg-1 , and 0.45 ± 0.03 L/kg, respectively. In the castration group, the t1/2 ʎz of meloxicam prolonged, AUC0-∞ increased, and ClT and Vdss decreased. In conclusion, the excretion of meloxicam from the body slowed and the t1/2 ʎz was prolonged in the castrated goat kids following xylazine administration. However, there is a need to determine the pharmacodynamics of meloxicam in castrated goat kids.

5.
J Vet Pharmacol Ther ; 43(3): 288-296, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32133667

RESUMO

The purpose of this study was to determine the influences of supportive therapy (ST) on the pharmacokinetics (PK) of marbofloxacin in lipopolysaccharide (LPS)-induced endotoxemic sheep. Furthermore, minimum inhibitory concentration (MIC) of marbofloxacin against Escherichia coli, Mannheimia haemolytica, Pasteurella multocida, Klebsiella pneumoniae, Salmonella spp., and Staphylococcus aureus was determined. The study was performed using a three-period cross PK design following a 15-day washout period. In the first period, marbofloxacin (10 mg/kg) was administered by an intravenous (IV) injection. In the second and third periods, marbofloxacin was co-administered with ST (lactated ringer + 5% dextrose + 0.45% sodium chloride, IV, 20 ml/kg, dexamethasone 0.5 mg/kg, SC) and ST + LPS (E. coli O55:B5, 10 µg/kg), respectively. Plasma marbofloxacin concentration was measured using HPLC-UV. Following IV administration of marbofloxacin alone, the t 1 / 2 λ z , AUC0-∞ , ClT , and Vdss were 2.87 hr, 34.73 hr × µg/ml, 0.29 L hr-1  kg-1 , and 0.87 L/kg, respectively. While no change was found in the MBX + ST group in terms of the PK parameters of marbofloxacin, it was determined that the ClT of marbofloxacin decreased, AUC0-∞ increased, and t 1 / 2 λ z and MRT prolonged in the MBX + ST + LPS group. MIC values of marbofloxacin were 0.031 to >16 µg/ml for E. coli, 0.016 to >16 µg/ml for M. haemolytica, 0.016-1 µg/ml for P. multocida, 0.016-0.25 µg/ml for K. pneumoniae, 0.031-0.063 µg/ml for Salmonella spp., and 0.031-1 µg/ml for S. aureus. The study results show the necessity to make a dose adjustment of marbofloxacin following concomitant administration of ST in endotoxemic sheep. Also, the PK and pharmacodynamic effect of marbofloxacin needs to be determined in naturally infected septicemic sheep following concomitant administration of single and ST.

6.
J Vet Pharmacol Ther ; 43(4): 319-324, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32212341

RESUMO

The aim of this study was to determine the effect of benzylpenicillin on the pharmacokinetics of acyclovir in red-eared slider turtles (Trachemys scripta elegans). Six clinically healthy red-eared slider turtles weighing 400 and 580 g were used for the study. Acyclovir (40 mg/kg) and benzylpenicillin (30 mg/kg) were administered intravenously to turtles. In the study, the cross-pharmacokinetic design (2 × 2) with a 30-day washout period was performed in two periods. Plasma concentrations of acyclovir were assayed using the high-performance liquid chromatography with fluorescence detection. Pharmacokinetic parameters were calculated by two-compartment open pharmacokinetic model. Following the administration of acyclovir alone, elimination half-life (t1/2 ß ), area under the plasma concentration-time curve (AUC), total clearance (ClT ), and volume of distribution at steady-state (Vdss ) were 20.12 hr, 1,372 hr * µg/mL, 0.03 L hr-1  kg-1 , and 0.84 L/kg, respectively. Benzylpenicillin administration increased t1/2 ß , AUC, and Vdss while decreased ClT of acyclovir. These results showed that benzylpenicillin changed the pharmacokinetics of acyclovir following simultaneous administration in turtles. However, further research is needed to determine molecular mechanism of interaction in turtle.

7.
J Vet Pharmacol Ther ; 43(2): 108-114, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32043623

RESUMO

In this study, the pharmacokinetics of moxifloxacin (5 mg/kg) was determined following a single intravenous administration of moxifloxacin alone and co-administration with diclofenac (2.5 mg/kg) or flunixin meglumine (2.2 mg/kg) in sheep. Six healthy Akkaraman sheep (2 ± 0.3 years and 53.5 ± 5 kg of body weight) were used. A longitudinal design with a 15-day washout period was used in three periods. In the first period, moxifloxacin was administered by an intravenous (IV) injection. In the second and third periods, moxifloxacin was co-administered with IV administration of diclofenac and flunixin meglumine, respectively. The plasma concentration of moxifloxacin was assayed by high-performance liquid chromatography. The pharmacokinetic parameters were calculated using a two-compartment open pharmacokinetic model. Following IV administration of moxifloxacin alone, the mean elimination half-life (t1/2ß ), total body clearance (ClT ), volume of distribution at steady state (Vdss ) and area under the curve (AUC) of moxifloxacin were 2.27 hr, 0.56 L h-1  kg-1 , 1.66 L/kg and 8.91 hr*µg/ml, respectively. While diclofenac and flunixin meglumine significantly increased the t1/2ß and AUC of moxifloxacin, they significantly reduced the ClT and Vdss . These results suggest that anti-inflammatory drugs could increase the therapeutic efficacy of moxifloxacin by altering its pharmacokinetics.

8.
Vet Anaesth Analg ; 46(5): 699-706, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31395485

RESUMO

OBJECTIVE: To determine the pharmacokinetics of tolfenamic acid (TA) after different routes of administration [intravenous (IV) and intramuscular (IM), 2 mg kg-1] and doses (IV, 2 and 4 mg kg-1) in red-eared slider turtles (Trachemys scripta elegans). STUDY DESIGN: Randomized experimental trial. ANIMALS: Sixteen healthy red-eared slider turtles. METHODS: Turtles were randomly assigned to two groups (n = 8 each). Group 1 received TA at a dose of 2 mg kg-1 IV and then IM, after a washout period of 30 days. Group 2 received 4 mg kg-1 TA IV. A noncompartmental analysis was used to calculate pharmacokinetic variables. RESULTS: No local and/or systemic adverse drug effects were observed in any turtle. Elimination half-life and mean residence time following IM administration at 2 mg kg-1 were significantly longer than those following IV administration. The bioavailability following IM administration was complete. The area under the plasma concentration-time curve, elimination half-life, mean residence time and total clearance were significantly different between the dose groups. CONCLUSIONS AND CLINICAL RELEVANCE: The absence of adverse reactions in the turtles of the study of TA along with the favourable pharmacokinetic properties (the long half-life and the complete bioavailability) of TA administered at the single doses of 2 and 4 mg kg-1 suggest the possibility of its effective use in turtles. However, further studies are required to establish a multiple dosage regimen of TA and to evaluate the clinical efficacy of administering TA.


Assuntos
Analgésicos/farmacocinética , Tartarugas/metabolismo , ortoaminobenzoatos/farmacocinética , Analgésicos/sangue , Animais , Injeções Intramusculares/veterinária , Injeções Intravenosas/veterinária , ortoaminobenzoatos/sangue
9.
Am J Vet Res ; 80(7): 702-708, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31246127

RESUMO

OBJECTIVE: To determine the pharmacokinetics of pentoxifylline (PTX) and its 5-hydroxyhexyl metabolite (M-I) after IV administration of increasing doses of PTX to sheep. ANIMALS: 6 healthy adult Merino sheep. PROCEDURES: Each sheep received 10-, 20-, and 40-mg/kg doses of PTX, IV, with a 15-day washout period between doses. Blood samples were collected before and at predetermined times after administration of each dose to determine plasma PTX and M-I concentrations by high-performance liquid chromatography. Pharmacokinetic parameters for PTX and M-I were estimated by noncompartmental analysis. RESULTS: No adverse effects were observed after administration of the 10- and 20-mg/kg doses. Following administration of the 40-mg/kg dose, all sheep developed tachycardia and hypersalivation and appeared agitated for approximately 4 hours. Plasma PTX concentrations considered therapeutic in other species were achieved in all sheep after administration of all 3 doses. Pharmacokinetic parameters for PTX and M-I varied in a dose-dependent linear manner. For PTX, the mean area under the concentration-time curve (AUC), elimination half-life, and volume of distribution increased with dose and ranged from 15.67 to 94.66 h·µg/mL, 0.68 to 0.91 hours, and 0.55 to 0.66 L/kg, respectively, whereas clearance decreased with dose and ranged from 0.42 to 0.64 L/h/kg. The mean ratio of the AUC for M-I to AUC for PTX ranged from 0.38 to 0.46. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that pharmacokinetic parameters for PTX and M-I varied in a dose-dependent linear manner in healthy sheep. Further studies are warranted to determine the therapeutic threshold and optimal dosage for PTX in sheep.


Assuntos
Pentoxifilina/farmacologia , Inibidores da Agregação de Plaquetas/farmacologia , Ovinos/metabolismo , Administração Intravenosa/veterinária , Animais , Área Sob a Curva , Cromatografia Líquida de Alta Pressão/veterinária , Estudos Cross-Over , Relação Dose-Resposta a Droga , Meia-Vida , Pentoxifilina/farmacocinética , Inibidores da Agregação de Plaquetas/farmacocinética , Distribuição Aleatória
10.
Trop Anim Health Prod ; 51(8): 2603-2610, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31230255

RESUMO

The study aimed to define the effects of M. haemolytica and a single oral dose of albendazole on the single-dose pharmacokinetics of marbofloxacin in lambs. The pharmacokinetic-pharmacodynamic integration of marbofloxacin was applied to describe a 3 mg/kg intramuscular dose in lambs. The 6 healthy and 12 naturally infected with M. haemolytica lambs (Akkaraman, males weighing 10-15 kg and aged 2-3 months) were used in this study. In the marbofloxacin group, 6 healthy lambs received marbofloxacin. In the albendazole group after 2 weeks washout period, the same animals received marbofloxacin on 1 h after albendazole. In the diseased marbofloxacin group, 6 lambs naturally infected with M. haemolytica received marbofloxacin. In the diseased albendazole group, 6 lambs naturally infected with M. haemolytica received marbofloxacin on 1 h after albendazole. The marbofloxacin and albendazole were administered each as a single dose of 3 mg/kg intramuscular and 7.5 mg/kg oral, respectively, in the respective groups. Plasma concentration of marbofloxacin was measured with HPLC-UV and pharmacokinetic parameters were analyzed by non-compartmental model. Albendazole did not change the pharmacokinetic profiles of marbofloxacin in healthy and diseased lambs. However, M. haemolytica affected the pharmacokinetics of marbofloxacin in diseased lambs, AUC0-24/MIC90 ratio was not found to be higher than 125, but Cmax/MIC90 ratios was found to be higher than 10 for an MIC value of 0.25 µg/mL in all groups. The marbofloxacin dose described in this study may not be effective for the treatment of infections due to M. haemolytica in lambs, with MIC ≤ 0.25 µg/mL.


Assuntos
Albendazol/farmacologia , Anti-Helmínticos/farmacologia , Antibacterianos/farmacocinética , Fluoroquinolonas/farmacocinética , Mannheimia haemolytica/fisiologia , Pasteurelose Pneumônica/tratamento farmacológico , Doenças dos Ovinos/tratamento farmacológico , Animais , Injeções Intramusculares/veterinária , Masculino , Pasteurelose Pneumônica/microbiologia , Ovinos , Doenças dos Ovinos/microbiologia , Turquia
11.
J Vet Pharmacol Ther ; 42(6): 624-631, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31190327

RESUMO

The aim of this study was to determine the pharmacokinetics/pharmacodynamics of enrofloxacin (ENR) and danofloxacin (DNX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. The study was performed on twenty-four calves that were determined to be premature by anamnesis and general clinical examination. Premature calves were randomly divided into four groups (six premature calves/group) according to a parallel pharmacokinetic (PK) design as follows: ENR-IV (10 mg/kg, IV), ENR-IM (10 mg/kg, IM), DNX-IV (8 mg/kg, IV), and DNX-IM (8 mg/kg, IM). Plasma samples were collected for the determination of tested drugs by high-pressure liquid chromatography with UV detector and analyzed by noncompartmental methods. Mean PK parameters of ENR and DNX following IV administration were as follows: elimination half-life (t1/2λz ) 11.16 and 17.47 hr, area under the plasma concentration-time curve (AUC0-48 ) 139.75 and 38.90 hr*µg/ml, and volume of distribution at steady-state 1.06 and 4.45 L/kg, respectively. Total body clearance of ENR and DNX was 0.07 and 0.18 L hr-1  kg-1 , respectively. The PK parameters of ENR and DNX following IM injection were t1/2λz 21.10 and 28.41 hr, AUC0-48 164.34 and 48.32 hr*µg/ml, respectively. The bioavailability (F) of ENR and DNX was determined to be 118% and 124%, respectively. The mean AUC0-48CPR /AUC0-48ENR ratio was 0.20 and 0.16 after IV and IM administration, respectively, in premature calves. The results showed that ENR (10 mg/kg) and DNX (8 mg/kg) following IV and IM administration produced sufficient plasma concentration for AUC0-24 /minimum inhibitory concentration (MIC) and maximum concentration (Cmax )/MIC ratios for susceptible bacteria, with the MIC90 of 0.5 and 0.03 µg/ml, respectively. These findings may be helpful in planning the dosage regimen for ENR and DNX, but there is a need for further study in naturally infected premature calves.


Assuntos
Animais Recém-Nascidos , Antibacterianos/farmacocinética , Bovinos/sangue , Enrofloxacina/farmacocinética , Fluoroquinolonas/farmacocinética , Nascimento Prematuro , Animais , Antibacterianos/sangue , Área Sob a Curva , Bactérias/efeitos dos fármacos , Bovinos/metabolismo , Enrofloxacina/sangue , Fluoroquinolonas/sangue , Meia-Vida , Testes de Sensibilidade Microbiana
12.
J Vet Pharmacol Ther ; 42(6): 632-639, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31197850

RESUMO

The aim of this study was to evaluate the pharmacokinetics and bioavailability of cefquinome (CFQ) and ceftriaxone (CTX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. Using a parallel design, 24 premature calves were randomly divided into the two antibiotic groups. Each of the six animals in the first group received CFQ (2 mg/kg) through IV or IM administration. The second group received CTX (20 mg/kg) via the same administration route. Plasma concentrations of the drugs were analyzed by high-performance liquid chromatography and noncompartmental methods. Mean pharmacokinetic parameters of CFQ and CTX following IV administration were as follows: elimination half-life (t1/2λz ) 1.85 and 3.31 hr, area under the plasma concentration-time curve (AUC0-∞ ) 15.74 and 174 hr * µg/ml, volume of distribution at steady-state 0.37 and 0.45 L/kg, and total body clearance 0.13 and 0.12 L hr-1  kg-1 , respectively. Mean pharmacokinetic parameters of CFQ and CTX after IM injection were as follows: peak concentration 4.56 and 25.04 µg/ml, time to reach peak concentration 1 and 1.5 hr, t1/2λz 4.74 and 3.62 hr, and AUC0-∞ 22.75 and 147 hr * µg/ml, respectively. The bioavailability of CFQ and CTX after IM injection was 141% and 79%, respectively. IM administration of CFQ (2 mg/kg) and CTX (20 mg/kg) can be recommended at 12-hr interval for treating infections caused by susceptible bacteria, with minimum inhibitory concentration values of ≤0.5 and ≤4 µg/ml, respectively, in premature calves. However, further research is indicated to assess the pharmacokinetic parameters following multiple doses of the drug in premature calves.


Assuntos
Animais Recém-Nascidos , Antibacterianos/farmacocinética , Bovinos/sangue , Ceftriaxona/farmacocinética , Cefalosporinas/farmacocinética , Nascimento Prematuro , Animais , Antibacterianos/sangue , Área Sob a Curva , Bactérias/efeitos dos fármacos , Bovinos/metabolismo , Ceftriaxona/sangue , Cefalosporinas/sangue , Meia-Vida , Testes de Sensibilidade Microbiana
13.
J Vet Pharmacol Ther ; 42(6): 654-659, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30933367

RESUMO

The pharmacokinetics and bioavailability of levamisole were determined in red-eared slider turtles after single intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration. Nine turtles received levamisole (10 mg/kg) by each route in a three-way crossover design with a washout period of 30 days. Blood samples were collected at time 0 (pretreatment), and at 0.25, 0.5, 1, 1.5, 3, 6, 9, 12, 18, 24, 36, and 48 hr after drug administration. Plasma levamisole concentrations were determined by a high-performance liquid chromatography assay. Data were analyzed by noncompartmental methods. The mean elimination half-life was 5.00, 7.88, and 9.43 hr for IV, IM, and SC routes, respectively. The total clearance and volume of distribution at steady state for the IV route were 0.14 L hr-1  kg-1 and 0.81 L/kg, respectively. For the IM and SC routes, the peak plasma concentration was 9.63 and 10.51 µg/ml, respectively, with 0.5 hr of Tmax . The bioavailability was 93.03 and 115.25% for the IM and SC routes, respectively. The IM and SC route of levamisole, which showed the high bioavailability and long t1/2ʎz , can be recommended as an effective way for treating nematodes in turtles.


Assuntos
Antinematódeos/farmacocinética , Levamisol/farmacocinética , Tartarugas/sangue , Animais , Antinematódeos/sangue , Área Sob a Curva , Disponibilidade Biológica , Estudos Cross-Over , Meia-Vida , Injeções Intramusculares , Injeções Intravenosas , Injeções Subcutâneas , Levamisol/sangue
14.
Acta Vet Hung ; 67(1): 87-97, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30922094

RESUMO

The administration of high doses of non-steroidal anti-inflammatory drugs (NSAID), such as tolfenamic acid (TA), has undesirable effects on different organs. Some novel biomarkers have been reported that can determine the gastrointestinal and renal injury caused by a high dose of NSAIDs or other toxic substances. This study was aimed at determining the changes in gastrointestinal (TFF2 and HYP), renal (NGAL and KIM-1) and cardiac (cTn-I, CK-MB) injury markers after the use of increasing intravenous doses of TA in sheep. TA was administered intravenously to groups of six sheep each, at the dose levels of 0 (Group 0, i.e., G0), 2 (G2), 4 (G4), 8 (G8) and 16 (G16) mg/kg. The concentrations of the studied biomarkers were measured at 3, 9, 18 and 36 h after administration of TA. The TFF2 and NGAL concentrations in G16 were found to be significantly higher (P < 0.05) than in the other groups except for G8 at different sampling times. HYP concentration in G16 was observed to be significantly (P < 0.05) lower than that in all other groups at 36 h. KIM-1 level in G16 was significantly (P < 0.05) higher than in all other groups at different sampling times. An increase in the renal markers, KIM-1 and NGAL, in G8 was observed before any change in plasma creatinine and urea. The cardiac marker cTn-I in G16 was significantly (P < 0.05) higher than in other groups at different sampling times. The results showed that the novel biomarkers (HYP, TFF2, NGAL, and KIM-1) can be used to determine gastric and renal injury in sheep.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Gastroenteropatias/veterinária , Nefropatias/veterinária , Doenças dos Ovinos/induzido quimicamente , ortoaminobenzoatos/administração & dosagem , Administração Intravenosa , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Biomarcadores/sangue , Relação Dose-Resposta a Droga , Feminino , Gastroenteropatias/sangue , Gastroenteropatias/induzido quimicamente , Nefropatias/sangue , Nefropatias/induzido quimicamente , Ovinos , Doenças dos Ovinos/sangue , ortoaminobenzoatos/efeitos adversos
15.
J Vet Med Sci ; 81(5): 753-757, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-30853667

RESUMO

This study aimed to investigate the pharmacokinetics of danofloxacin in red-eared slider turtle (Trachemys scripta elegans) following a single intravenous (IV) and intramuscular (IM) administrations of 6 mg/kg, using a two-way crossover study with 30-day washout period. Eight clinically healthy red-eared slider turtle weighing 410-600 g (mean 490 g) were used for the study. Danofloxacin concentrations were measured using the reversed-phase high-performance liquid chromatography. The plasma concentration-time data were evaluated by a non-compartmental method. After IV administration, the elimination half-life (t1/2ʎz), mean residence time (MRT0-∞), area under the concentration-time curve (AUC0-∞), volume of distribution at steady state and total body clearance in plasma were 24.17 hr, 30.64 hr, 143.31 hr·µg/ml, 1.29 l/kg and 0.04 l/hr/kg, respectively. Following IM administration, t1/2ʎz, MRT0-∞, AUC0-∞, peak concentration (Cmax), time to reach Cmax, and bioavailability in plasma were 32.00 hr, 41.15 hr, 198.23 hr·µg/ml, 8.75 µg/ml, 1.5 hr and 139.89%, respectively. Danofloxacin has clinically superior pharmacokinetic properties, including the complete IM absorption, slow elimination and wide volume of distribution in red-eared slider turtles. However, further pharmacokinetics/pharmacodynamics studies are necessary for the treatment of diseases caused by susceptible bacteria with known minimum inhibitory concentration values in red-eared slider turtles.


Assuntos
Anti-Infecciosos/farmacocinética , Fluoroquinolonas/farmacocinética , Tartarugas , Animais , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/sangue , Disponibilidade Biológica , Estudos Cross-Over , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/sangue , Injeções Intramusculares/veterinária , Injeções Intravenosas/veterinária
16.
J Vet Pharmacol Ther ; 42(6): 647-653, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30719732

RESUMO

The purpose of this study was to determine the pharmacokinetics of cefquinome (CFQ) following single and repeated subcutaneous (SC) administrations in sheep. Six clinically healthy, 1.5 ± 0.2 years sheep were used for the study. In pharmacokinetic study, the crossover design in three periods was performed. The withdrawal interval between the study periods was 15 days. In first period, CFQ (Cobactan, 2.5%) was administered by an intravenous (IV) bolus (3 sheep) and SC (3 sheep) injections at 2.5 mg/kg dose. In second period, the treatment administration was repeated via the opposite administration route. In third period, CFQ was administrated subcutaneously to each sheep (n = 6) at a dose of 2.5 mg/kg q. 24 hr for 5 days. Plasma concentrations of CFQ were measured using the HPLC-UV method. Pharmacokinetic parameters were calculated using non-compartmental methods. The elimination half-life and mean residence time of CFQ after the single SC administration were longer than IV administration (p < 0.05). Bioavailability (F%) of CFQ following the single SC administration was 123.51 ± 11.54%. The area under the curve (AUC0-∞ ) and peak concentration following repeated doses (last dose) were higher than those observed after the first dose (p < 0.05). CFQ accumulated after repeated SC doses. CFQ can be given via SC at a dose of 2.5 mg/kg every 24 hr for the treatment of infections caused by susceptible pathogens, which minimum inhibitory concentration is ≤1.0 µg/ml in sheep.


Assuntos
Cefalosporinas/farmacocinética , Ovinos/sangue , Animais , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Antibacterianos/farmacocinética , Área Sob a Curva , Bactérias/efeitos dos fármacos , Cefalosporinas/administração & dosagem , Cefalosporinas/sangue , Esquema de Medicação , Meia-Vida , Injeções Subcutâneas , Testes de Sensibilidade Microbiana , Ovinos/metabolismo
17.
Trop Anim Health Prod ; 51(2): 435-441, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30219998

RESUMO

This study investigated the pharmacokinetics of pentoxifylline (PTX) and its 5-hydroxyhexyl metabolite (M-I) after single-dose intravenous (IV) administration (10 mg/kg) of PTX in six healthy cattle. The safety of PTX was evaluated by clinical observation and biochemical analysis. Plasma concentrations of PTX and M-I were simultaneously determined by reverse-phase high performance liquid chromatography. Pharmacokinetic parameters were calculated using non-compartmental methods. Salivation and discomfort were observed for 2 h following the drug administration. Serum direct bilirubin, total bilirubin, and phosphorus levels at 24 h following the drug administration were significantly different from the control values (0 h) (P < 0.05). Pharmacokinetic variables of PTX were characterized by a short terminal elimination half-life (1.05 ± 0.19 h), a large volume of distribution (6.30 ± 1.76 L/kg), and high total body clearance (5.31 ± 1.27 L/h/kg). The mean ratio between the area under the concentration-time curves of M-I and PTX was 1.34. These results indicate that single-dose administration of PTX at 10 mg/kg IV in cattle resulted in therapeutic concentrations similar to those observed in humans and horse. However, further studies are necessary to determine the safety and pharmacokinetics following repeated administrations of PTX.


Assuntos
Bovinos , Pentoxifilina/farmacocinética , Inibidores de Fosfodiesterase/farmacocinética , Administração Intravenosa , Animais , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Meia-Vida , Injeções Intravenosas , Pentoxifilina/administração & dosagem , Pentoxifilina/metabolismo , Inibidores de Fosfodiesterase/administração & dosagem , Inibidores de Fosfodiesterase/metabolismo
18.
J Vet Pharmacol Ther ; 42(2): 207-213, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30474236

RESUMO

The aim of the present study was to determine the pharmacokinetics (PKs) and bioavailability of danofloxacin in chukar partridge (Alectoris chukar) following intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations at a dose of 10 mg/kg. A total of eight clinically healthy chukar partridges weighing 480 ± 45 g were used for the investigation. The study was performed in a crossover design (2 × 2 × 2 × 2) with a 15-day washout period between two administrations in four periods. The plasma concentrations of danofloxacin were determined using reversed-phase high-performance liquid chromatography. Noncompartmental PK parameters were also estimated. No local or systemic adverse drug effects were observed in any of the chukar partridges. The mean elimination half-life ranged between 8.18 and 12.08 hr and differed statistically among administration routes. The mean peak plasma concentrations of danofloxacin following IM, SC, and PO administrations were 8.05, 9.58, and 3.39 µg/ml at 0.5, 1, and 4 hr, respectively. Following IM, SC, and PO administrations, the mean bioavailability was 86.33%, 134.40%, and 47.62%, respectively. The mean total clearance and volume of distribution at steady-state following IV administration were 0.13 L hr-1  kg-1 and 0.96 L/kg, respectively. These data, including favorable PKs and the absence of adverse drug effects, suggest that danofloxacin is a useful antibiotic in chukar partridges.


Assuntos
Antibacterianos/farmacocinética , Fluoroquinolonas/farmacocinética , Galliformes/metabolismo , Administração Oral , Animais , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão/veterinária , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/sangue , Galliformes/sangue , Meia-Vida , Injeções Intramusculares/veterinária , Injeções Intravenosas/veterinária , Injeções Subcutâneas/veterinária
19.
Artigo em Inglês | MEDLINE | ID: mdl-30352010

RESUMO

Plasma and muscle pharmacokinetics of danofloxacin were investigated after 10 mg/kg intravenous (IV, caudal vein) and intramuscular (IM, right epaxial muscles) administrations in 168 healthy brown trout (Salmo trutta fario) at 10°C-13°C. High-performance liquid chromatography was used to determine its plasma and muscle concentrations. Pharmacokinetic parameters were analysed with a non-compartmental model. After IV administration, elimination half-life (t1/2ʎz), area under the concentration-time curve (AUC0-∞), mean residence time (MRT0-∞), volume of distribution at steady state, total body clearance in plasma and AUCMuscle/AUCPlasma ratio were 22.22 h, 140.66 h*µg/mL, 23.15 h, 2.28 L/kg, 0.07 L/h/kg and 3.79, respectively. After IM administration, t1/2ʎz, AUC0-∞, MRT0-∞, peak concentration (Cmax), time to reach Cmax, bioavailability in plasma and AUCMuscle/AUCPlasma ratio were 28.28 h, 84.39 h*µg/mL, 37.31 h, 4.79 µg/mL, 1 h, 59.99% and 8.46, respectively. Danofloxacin exhibited long t1/2ʎz and good bioavailability after IM administration. Therefore, 10 mg/kg IM administration of danofloxacin in brown trout can provide AUC0-24/MIC of > 125 and Cmax/MIC of > 10 to treat diseases caused by susceptible bacteria with ≤ 0.336 µg/mL MIC.


Assuntos
Fluoroquinolonas/sangue , Fluoroquinolonas/farmacocinética , Truta/sangue , Truta/metabolismo , Administração Intravenosa , Animais , Cromatografia Líquida de Alta Pressão , Fluoroquinolonas/administração & dosagem , Injeções Intramusculares , Músculos/metabolismo , Distribuição Tecidual
20.
J Vet Pharmacol Ther ; 41(6): 871-877, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30084126

RESUMO

The pharmacokinetics, bioavailability, and tolerability of tolfenamic acid (TA) were determined after treating sheep with TA via different routes and doses. This crossover study was carried out with a washout period of 15 days. In the study, 16 clinically healthy sheep were randomly assigned to two equal groups. In the first group (n = 8), animals received TA by intravenous (IV), intramuscular (IM), subcutaneous (SC), or oral (OR) routes at 2 mg/kg. In the second group (n = 8), TA was administered intravenously to each sheep at 2, 4, 8, and 16 mg/kg. Plasma samples were analyzed with a high-performance liquid chromatography assay. Noncompartmental pharmacokinetic analyses were used to evaluate the data. The area under the concentration-time curves (AUC0-∞ ), elimination half-life (t1/2ʎz ), and the mean residence time (MRT) significantly differed among the administration routes at 2 mg/kg of TA. Following IM, SC, and OR administrations, TA demonstrated different peak concentrations (Cmax ) and time to reach Cmax (Tmax ), with a bioavailability of 163%, 127%, and 107%, respectively. The dose-normalized AUC0-∞ revealed a significant difference among the dose groups; however, the relationship between dose and AUC0-∞ was linear. Both t1/2ʎz and MRT increased depending on the dose. Although the total clearance (ClT ) decreased depending on dose, the volume of distribution at steady-state (Vss ) increased. Tolfenamic acid indicated a long half-life and high bioavailability following IM, SC, and OR administrations at 2 mg/kg. TA exhibited linear kinetics and was well tolerated by the animals, except at 16 mg/kg. Thus, TA may be used in different routes and doses (≤8 mg/kg) in sheep; however, further studies are needed to determine the clinical efficacy of TA during the inflammatory and painful conditions and the pharmacokinetics and safety of repeated administration in sheep.


Assuntos
Analgésicos/farmacocinética , Ovinos/sangue , ortoaminobenzoatos/farmacocinética , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Analgésicos/sangue , Animais , Área Sob a Curva , Disponibilidade Biológica , Estudos Cross-Over , Relação Dose-Resposta a Droga , Vias de Administração de Medicamentos , Meia-Vida , Distribuição Aleatória , ortoaminobenzoatos/administração & dosagem , ortoaminobenzoatos/efeitos adversos , ortoaminobenzoatos/sangue
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