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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.
Artigo em Inglês | MEDLINE | ID: mdl-32613470

RESUMO

BACKGROUND AND OBJECTIVE: The antitumor activity and toxicity of doxorubicin are potentiated and attenuated by calcitriol, respectively. Potentially, calcitriol can be combined with doxorubicin for clinical benefit in chemotherapy. To gain insight into the interaction between doxorubicin and calcitriol, proposed for combined use in cancer treatment, we studied calcitriol's effect on the plasma pharmacokinetics, tissue distribution and excretion of doxorubicin in female and male mice. METHODS: The control and calcitriol-treated groups, including an equal number of both sexes, received corn oil and calcitriol (2.5 µg/kg), respectively, intraperitoneally every other day for 8 days. At day 9, doxorubicin was administered intraperitoneally at a 6 mg/kg dose to each group. Doxorubicin concentrations in biologic specimens were determined by a high-performance liquid chromatographic-ultraviolet detector and analyzed using a non-compartmental model. RESULTS: The plasma pharmacokinetics of doxorubicin were similar in the control and calcitriol-treated groups. While calcitriol did not alter the area under the plasma concentration-time curves (AUCs) and peak concentrations (Cmax) of doxorubicin in the small intestine and testis, it significantly reduced the AUCs and Cmax of doxorubicin in the lung, kidney, spleen, liver, stomach and ovaries. However, calcitriol increased the AUCs and Cmax of doxorubicin in the heart of females, brain of males and duodenum content and vitreous humor of female and male mice. The percent cumulative urine and fecal amounts of doxorubicin in calcitriol-treated mice were higher at 89.23% and 29.37% for female mice and 118.57% and 41.65% for male mice than those in the control mice, respectively. CONCLUSIONS: The tissue concentrations and excretion of doxorubicin in both female and male mice are influenced by calcitriol without changes in the plasma pharmacokinetics. The results from this study can provide insights to help obtain the optimal drug combination effects of doxorubicin with calcitriol in cancer treatment.

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.
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.

6.
Mitochondrion ; 52: 83-88, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32119925

RESUMO

To determine the effects of alpha lipoic acid (ALA) and vitamin E (Vit E) on mitochondrial dysfunction caused by statins. A total of 38 Wistar Albino rats were used in this study. The control group received dimethyl sulfoxide. The atorvastatin (A) group received atorvastatin (10 mg/kg). The A + ALA group received atorvastatin (10 mg/kg) and ALA (100 mg/kg). The A + Vit E group was administered atorvastatin (10 mg/kg) and Vit E (100 mg/kg). The A + ALA + Vit E group was administered atorvastatin (10 mg/kg), ALA (100 mg/kg) and Vit E (100 mg/kg). All applications were administered simultaneously by gavage for 20 days. ATP level and complex I activity were measured from liver, muscle, heart, kidney and brain. Atorvastatin significantly decreased the ATP levels in heart and kidney, while a slight decrease was seen in liver, muscle and brain. Atorvastatin caused an insignificant decrease in the complex I activity in all tissues examined. ALA administration significantly improved the ATP levels in the liver, heart and kidney, while Vit E improved the ATP levels in all tissues except the muscle compared to Atorvastatin group. Single administration of both ALA and vit E ameliorated complex I activity in the muscle, heart, kidney and brain. The combination of ALA and Vit E significantly improved the ATP levels in the liver, heart, kidney and brain and also provided significant improvements the complex I activity in all tissues. The undesirable effects of Atorvastatin on mitochondrial functions in this study ameliorated by using ALA and/or Vit E alone and in combination.

7.
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.

8.
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.

9.
Am J Vet Res ; 81(2): 139-146, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31985285

RESUMO

OBJECTIVE: To evaluate the usefulness of intestinal biomarkers in determining the presence of intestinal epithelial damage in neonatal calves with diarrhea caused by 4 etiologic agents. ANIMALS: 40 neonatal calves that were healthy (n = 10) or had diarrhea (30). PROCEDURES: The study was a cross-sectional study. Results of hematologic analyses and serum concentrations of intestinal fatty acid-binding protein (I-FABP), liver fatty acid-binding protein (L-FABP), trefoil factor 3 (TFF-3), Claudin-3 (CLDN-3), γ-enteric smooth muscle actin (ACTG2), intestinal alkaline phosphatase (IAP), interleukin-8 (IL-8), platelet-activating factor (PAF), and leptin (LP) were compared among calves grouped according to whether they were healthy (control group; G-1) or had diarrhea caused by K99 Escherichia coli (G-2; n = 10), bovine rota- or coronavirus (G-3; 5 each), or Cryptosporidium spp (G-4; 10). RESULTS: Across the 3 time points at which blood samples were obtained and evaluated, the groups of calves with diarrhea generally had markedly higher mean serum concentrations of L-FABP, TFF-3, IAP, IL-8, and LP, compared with the control group. In addition, G-2 also consistently had markedly higher mean serum concentrations of I-FAB and ACTG2 and lower mean serum concentrations of CLDN-3, compared with the control group. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that degree of intestinal epithelial damage differed among calves grouped by the etiologic agent of diarrhea and that such damage might have been more severe in calves with diarrhea caused by K99 E coli. Additionally, our results indicated that serum concentrations of I-FABP, L-FABP, TFF-3, IAP, IL-8, ACTG2, LP, and CLDN-3 were useful biomarkers of intestinal epithelial damage in calves of the present study.


Assuntos
Doenças dos Bovinos , Criptosporidiose , Cryptosporidium , Animais , Biomarcadores , Bovinos , Estudos Transversais , Diarreia/veterinária , Escherichia coli , Fezes , Recém-Nascido , Intestinos
10.
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
11.
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
12.
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
13.
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
14.
J Vet Pharmacol Ther ; 42(5): 497-504, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31183888

RESUMO

The purpose of this study was to determine the pharmacokinetic interaction between ivermectin (0.4 mg/kg) and praziquantel (10 mg/kg) administered either alone or co-administered to dogs after oral treatment. Twelve healthy cross-bred dogs (weighing 18-21 kg, aged 1-3 years) were allocated randomly into two groups of six dogs (four females, two males) each. In first group, the tablet forms of praziquantel and ivermectin were administered using a crossover design with a 15-day washout period, respectively. Second group received tablet form of ivermectin plus praziquantel. The plasma concentrations of ivermectin and praziquantel were determined by high-performance liquid chromatography using a fluorescence and ultraviolet detector, respectively. The pharmacokinetic parameters of ivermectin following oral alone-administration were as follows: elimination half-life (t1/2λz ) 110 ± 11.06 hr, area under the plasma concentration-time curve (AUC0-∞ ) 7,805 ± 1,768 hr. ng/ml, maximum concentration (Cmax ) 137 ± 48.09 ng/ml, and time to reach Cmax (Tmax ) 14.0 ± 4.90 hr. The pharmacokinetic parameters of praziquantel following oral alone-administration were as follows: t1/2λz 7.39 ± 3.86 hr, AUC0-∞ 4,301 ± 1,253 hr. ng/ml, Cmax 897 ± 245 ng/ml, and Tmax 5.33 ± 0.82 hr. The pharmacokinetics of ivermectin and praziquantel were not changed, except Tmax of praziquantel in the combined group. In conclusion, the combined formulation of ivermectin and praziquantel can be preferred in the treatment and prevention of diseases caused by susceptible parasites in dogs because no pharmacokinetic interaction was determined between them.


Assuntos
Antiparasitários/farmacocinética , Cães/sangue , Ivermectina/farmacocinética , Praziquantel/farmacocinética , Administração Oral , Animais , Antiparasitários/administração & dosagem , Área Sob a Curva , Interações Medicamentosas , Feminino , Meia-Vida , Ivermectina/administração & dosagem , Ivermectina/sangue , Masculino , Praziquantel/administração & dosagem , Praziquantel/sangue
15.
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
16.
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
17.
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
18.
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
19.
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
20.
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
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