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1.
N Z Vet J ; 70(6): 313-318, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35852416

RESUMO

AIMS: To assess the pharmacokinetic profile of ivermectin in Bilgorajska geese (Anser anser domesticus) after single I/V or oral administration, in order to compare these routes of administration and assess oral bioavailability. METHODS: Ten healthy male geese were used in a single-dose, two-phase study with a 3-month washout period between phases. In the first phase, all geese were given 0.2 mg/kg I/V ivermectin, while in the second phase they were treated orally with the same dosage. Blood samples were collected at selected time points up to 480 hours after each administration. Samples were purified using protein precipitation and drug concentration was quantified using HPLC. The analytical method was validated on blank goose plasma and was characterised by an optimal linearity and a limit of quantification of 0.025 µg/mL. The pharmacokinetic analysis was carried out using a non-compartmental approach. RESULTS: The drug was quantifiable up to 240 hours after I/V administration, while after oral treatment it was quantifiable up to 144 hours in most of the geese. The elimination half-life of ivermectin was approximately 3.8 (95% CI = 1.98-7.92; p = 0.027) times higher after I/V administration compared to oral administration. Moreover, the area under the curve from zero to the last detectable timepoint was 6.4 (95% CI = 4.65-8.74; p < 0.001) hours greater after I/V than oral administration. This difference led to a bioavailability of 20.38 (SD 5.92) %. CONCLUSIONS: Following oral administration in geese, ivermectin has a bioavailability of approximately 20%. Further research on the action of ivermectin in the gastrointestinal tract is required along with assessment of tissue residues to allow calculation of withdrawal time to ensure consumer safety. ABBREVIATIONS: AUC: Area under the concentration-time curve; AUClast: Area under the curve from zero to the last detectable timepoint; AUMC: Area under the first moment curve; Cmax: Maximum concentration; Tmax: Time at maximum plasma concentration.


Assuntos
Gansos , Ivermectina , Administração Intravenosa/veterinária , Administração Oral , Animais , Área Sob a Curva , Disponibilidade Biológica , Meia-Vida , Masculino
2.
Br Poult Sci ; 63(4): 493-498, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35118922

RESUMO

1. Although amoxicillin has broad-spectrum antibiotic activity and is extensively used in poultry, its use has never been investigated in geese. This study aimed to evaluate the pharmacokinetics of amoxicillin after a single and multiple oral doses in geese.2. A total of 20 geese were enrolled in this study and randomly pooled in two groups (n = 10). In group I, animals were treated with a single oral 20 mg/kg dose of amoxicillin, while geese in group II were administered multiple doses (20 mg/kg/day for 4 d). Concentrations of amoxicillin in plasma were analysed using a validated HPLC-UV method and drug plasma concentrations were modelled for each subject using a non-compartmental approach.3. amoxicillin showed rapid absorption after a single-dose treatment, with an elimination half-life of approximately 1 h. Cmax, Tmax and AUC values differed statistically between groups I and II (after the first dose administered). A large variability was observed in the pharmacokinetic profiles and drug accumulation may occur after the multiple administration.4. No accumulation in plasma was predicted from an in-silico simulation performed using the same multiple dosage schedule. The in-silico simulation does not seem to accurately predict in-field conditions.


Assuntos
Amoxicilina , Gansos , Administração Oral , Amoxicilina/farmacocinética , Animais , Área Sob a Curva , Galinhas , Meia-Vida
3.
Br Poult Sci ; 62(2): 193-198, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33121260

RESUMO

1. The aim of this study was to assess the pharmacokinetics of levofloxacin, a third-generation fluoro-quinolone antimicrobial drug, in geese (n = 26) after either single intravenous or oral administration, and to evaluate the depletion profile in goose muscle, heart, liver, kidney and lung after a single oral dose.2. The pharmacokinetic study involved 16 geese which were randomly divided into two groups (n = 8/group), the first received levofloxacin (2 mg/kg) intravenously while the second was treated with orally (5 mg/kg). The tissue depletion study involved 10 geese which were dosed orally (5 mg/kg) and two animals were killed at different time-points in order to collect the selected tissues. Levofloxacin was quantified in all the matrices tested by a validated high-performance liquid chromatography (HPLC) method, using a spectrofluorimetric detector. The pharmacokinetics were analysed using a non-compartmental model.3. Plasma concentrations were quantified after up to 24 h in animals administered intravenously and up to 48 h after oral treatment. Levofloxacin was rapidly absorbed after oral administration (Tmax = 0.38 h) showing high bioavailability (95.57 ± 20.61%). The drug showed a moderate volume of distribution (1.40 ± 0.28 ml/g) and rapid clearance (0.28 ± 0.06 ml/g/h). No statistical differences in estimates were found between the two different administration methods (P > 0.05). Drug residues were highest at 6 h and decreased constantly up to 48 h in all the selected tissues. Liver and kidney had the highest levofloxacin concentrations.4. According to the pharmacokinetic/pharmacodynamic surrogate index (AUC/MIC) the levofloxacin dose regimen (after oral administration) used in the present study could be active against bacteria at a minimum inhibitory concentration (MIC) > 0.24  µg/ml in geese. In addition, drug accumulation in the liver might be controlled using an estimated preliminary withdrawal time of 90 h.


Assuntos
Gansos , Levofloxacino , Administração Oral , Animais , Antibacterianos , Área Sob a Curva , Galinhas , Ofloxacino
4.
N Z Vet J ; 68(1): 31-37, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31437418

RESUMO

Aims: To determine the pharmacokinetics and tissue depletion of 2 mg/kg marbofloxacin (MBX) in Bilgorajska geese (Anser anser domesticus) after I/V and oral administration, to calculate the daily dose from experimental data and to compare it with that calculated by allometric scaling.Methods: Eight clinically normal female Bilgorajska geese were used in a three-phase study with a 3-week wash-out period between phases. In the first phase birds received I/V administration of 2 mg/kg MBX; the same dose was given orally in the second and third phases. Blood samples were collected between 0 minutes and 48 hours in the first and second phases, and samples of liver, kidney, lung, muscle and heart were collected following slaughter of birds between 6 and 48 hours in the third phase. Concentrations of MBX in plasma and tissues were analysed using HPLC. Two additional birds served as controls. The optimal dose was calculated based on a minimal inhibitory concentration (MIC) of 0.125 µg/mL using the observed clearance, or using clearance calculated by allometric scaling.Results: Concentrations of MBX in plasma were detectable up to 24 hours following both I/V and oral administration. Mean oral bioavailability was 26.5 (SD 7.7)%. Concentrations of MBX in all tissues were highest at 6 hours and decreased constantly up to 34 hours. The mean optimal daily dose for oral administration of MBX, calculated using the observed clearance was 10.36 (SD 2.18) mg/kg, and using predicted clearance was 5.54 (SD 0.14) mg/kg. The preliminary withdrawal time for a maximum residue limit of 0.15 mg/kg calculated for muscle was 38.4 hours, heart 33.6 hours, kidney 48.3 hours, lung 47.7 hours and liver 49.3 hours.Conclusion and Clinical Relevance: There was insufficient evidence to recommend MBX orally administered to geese at a daily dose of 2 mg/kg for treatment of bacteria with an MIC of 0.125 µg/mL. Further pharmacokinetic/pharmacodynamic studies in geese are recommended to determine the MBX dose regimen and its clinical efficacy in geese.


Assuntos
Anseriformes/sangue , Antibacterianos/farmacocinética , Fluoroquinolonas/farmacocinética , Administração Intravenosa/veterinária , Administração Oral , Animais , Antibacterianos/administração & dosagem , Antibacterianos/metabolismo , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Resíduos de Drogas , Escherichia coli/efeitos dos fármacos , Feminino , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/metabolismo , Rim/química , Fígado/química , Pulmão/química , Músculo Esquelético/química , Miocárdio/química , Consumo de Álcool por Menores
5.
Pol J Vet Sci ; 21(2): 281-285, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30450866

RESUMO

Ibudilast (AV-411) is a non-selective inhibitor of cyclic nucleotide phosphodiesterase (PDE). It is currently marketed for human use in Asian countries for the treatment of asthma, cerebrovascular disorders and ocular allergies. Ibudilast has also been found to have an analgesic action for neuropathic pain at doses 5-10 times higher than those used in asthma therapy. Six healthy Labrador dogs were randomly assigned to two treatment groups using an open, single-dose, two-treatment, two-phase, cross-over design (2x2 Latin-square). Dogs in group 1 (n=3) were fasted for at least 10 hours overnight before the beginning of the experiment and 4 h following dosing while dogs in group 2 (n=3) received food ad libitum. During the first phase, each dog in group 1 and 2 received a single dose of 5 mg/kg ibudilast administered orally. After 1-week washout period the groups were rotated and the experiment was repeated. The analytical method, validated for dog plasma, was shown to be linear in the range 0.10-20 µg/mL. The limit of detection (LOD) and quantification (LOQ) were 0.03 and 0.1 µg/mL, respectively. No behavioural or health alterations were observed in the animals during or after the study. Ibudilast was detectable in plasma for up to 24 h showing a wide variability between animals. Although no statistically significant differences were observed in the present study between the fed and fasted states, examination of the raw data suggests that an effect may be present. The wide degree of variation observed in area under the curve (AUC) suggests that the investigation of population pharmacokinetic modelling is warranted.


Assuntos
Interações Alimento-Droga , Inibidores de Fosfodiesterase , Piridinas , Administração Oral , Animais , Área Sob a Curva , Estudos Cross-Over , Cães , Jejum , Inibidores de Fosfodiesterase/farmacocinética , Piridinas/farmacocinética
6.
J Vet Pharmacol Ther ; 41(3): 428-436, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29352476

RESUMO

Metamizole (MT), an analgesic and antipyretic drug, is rapidly hydrolyzed to the active primary metabolite 4-methylaminoantipyrine (MAA) and relatively active secondary metabolite 4-aminoantipyrine (AA). The aim of this study was to assess the pharmacokinetic profiles of MAA and AA after dose of 25 mg/kg MT by intravenous (i.v.), intramuscular (i.m.), oral (p.o.), and rectal (RC) routes in dogs. Six dogs were randomly allocated to an open, single-dose, four-treatment, four-phase, unpaired, crossover study design. Blood was collected at predetermined times within 24 hr, and plasma was analyzed by a validated HPLC-UV method. Plasma concentrations of MAA and AA after i.v., i.m., p.o., and RC administrations of MT were detectable from 5 (i.v. and i.m.) or 30 (p.o. and RC) min to 24 hr in all dogs. The highest concentrations of MAA were found in the i.v., then i.m., p.o., and RC groups. Plasma concentrations of AA were similar for i.v., i.m., and RC, and the concentrations were approximately double those in the PO groups. The AUCEV/IV ratio for MAA was 0.75 ± 0.11, 0.59 ± 0.08, and 0.32 ± 0.05, for i.m., p.o., and RC, respectively. The AUCEV/IV ratio for AA was 1.21 ± 0.33, 2.17 ± 0.62, and 1.08 ± 0.19, for i.m., p.o., and RC, respectively. Although further studies are needed, rectal administration seems to be the least suitable route of administration for MT in the dog.


Assuntos
Ampirona/farmacocinética , Anti-Inflamatórios não Esteroides/farmacocinética , Dipirona/farmacocinética , Administração Oral , Administração Retal , Ampirona/administração & dosagem , Ampirona/sangue , Ampirona/química , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/sangue , Anti-Inflamatórios não Esteroides/química , Área Sob a Curva , Estudos Cross-Over , Dipirona/administração & dosagem , Dipirona/sangue , Dipirona/química , Cães , Feminino , Meia-Vida , Injeções Intramusculares , Injeções Intravenosas , Estrutura Molecular
7.
J Vet Pharmacol Ther ; 41(2): 334-339, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29164623

RESUMO

This study was performed to determine pharmacokinetic profiles of the two active metabolites of the analgesic drug metamizole (dipyrone, MET), 4-methylaminoantipyrine (MAA), and 4-aminoantipyrine (AA), after intravenous (i.v., intramuscular (i.m.), and oral (p.o.) administration in cats. Six healthy mixed-breed cats were administered MET (25 mg/kg) by i.v., i.m., or p.o. routes in a crossover design. Adverse clinical signs, namely salivation and vomiting, were detected in all groups (i.v. 67%, i.m. 34%, and p.o. 15%). The mean maximal plasma concentration of MAA for i.v., i.m., and p.o. administrations was 148.63 ± 106.64, 18.74 ± 4.97, and 20.59 ± 15.29 µg/ml, respectively, with about 7 hr of half-life in all routes. Among the administration routes, the area under the plasma concentration curve (AUC) value was the lowest after i.m. administration and the AUCEV/i.v . ratio was higher in p.o. than the i.m. administration without statistical significance. The plasma concentration of AA was detectable up to 24 hr, and the mean plasma concentrations were smaller than MAA. The present results suggest that MET is converted into the active metabolites in cats as in humans. Further pharmacodynamics and safety studies should be performed before any clinical use.


Assuntos
Analgésicos/farmacocinética , Dipirona/farmacocinética , Administração Oral , Ampirona/sangue , Analgésicos/administração & dosagem , Animais , Gatos , Estudos Cross-Over , Dipirona/administração & dosagem , Dipirona/análogos & derivados , Dipirona/sangue , Injeções Intramusculares/veterinária , Injeções Intravenosas/veterinária , Masculino
8.
J Vet Pharmacol Ther ; 40(6): e11-e15, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28459136

RESUMO

Drugs that provide effective analgesia in cats are limited. The aim of the study was to assess the pharmacokinetics of grapiprant after 2 mg/kg administration via p.o. and i.v. routes in cats. Six healthy adult cats were used according to an open, single-dose, two-treatment, two-period, randomized cross-over design. Cats were assigned to two treatment groups and administered with 2 mg/kg of grapiprant (pure powder) through p.o. and i.v. administration. Blood samples were collected at preassigned times and analysed by a validated HPLC method. After both administrations, grapiprant concentrations were detectable in plasma for up to 24 hr in five of six animals. The critical parameters including clearance (173.2 ml hr-1  kg-1 , range 120-326 ml hr-1  kg-1 ) and volume of distribution (918 ml/kg, range 611-1608 ml/kg) were calculated from the i.v. group. The mean oral F% was low (39.6% range 31.5%-45.2%). If the assumption that the minimal effective concentration in dogs (164 ng/ml) applies in cats too, grapiprant orally administered at 2 mg/kg might be effective for 10 hr. Further studies are necessary to establish the minimal effective concentration in this animal species.


Assuntos
Receptores de Prostaglandina E Subtipo EP4/antagonistas & inibidores , Compostos de Sulfonilureia/farmacocinética , Administração Oral , Animais , Gatos , Estudos Cross-Over , Injeções Intravenosas/veterinária , Masculino , Compostos de Sulfonilureia/administração & dosagem , Compostos de Sulfonilureia/sangue
9.
N Z Vet J ; 65(1): 19-23, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27691904

RESUMO

AIMS: To assess the effect of food intake on the pharmacokinetics of grapiprant administered orally at 2 mg/kg, and to estimate its oral bioavailability in dogs. METHODS: Eight healthy female Labrador Retriever dogs, aged 4-10 years were used. In the initial trial two dogs were administered a 0.5 mg/kg I/V bolus of grapiprant dissolved in ethanol. In the second trial, six dogs were assigned to two treatment groups, using a randomised cross-over design, and received 2 mg/kg of grapiprant orally, as pure powder, after fasting for 12 hours or after being fed. Blood samples were collected at preassigned times up to 36 hours after administration, and concentrations of grapiprant in plasma determined using validated high performance liquid chromatography. RESULTS: After I/V administration in the two dogs the terminal half life was 5.30 and 6.06 hours, clearance was 444 and 476 mL/hours/kg, and volume of distribution was 3,642 and 3,883 mL/kg. Compared with fasted dogs, oral administration in fed dogs resulted in reduced median peak concentrations in plasma (1,598 vs. 614 ng/mL) and delayed median time of peak concentration (1.0 vs. 3.0 hours). The estimated bioavailability in fasted and fed dogs was 111.9 and 59.1%, respectively. Concentrations of grapiprant in plasma following oral administration, in either fed or fasted dogs, remained higher than 164 ng/mL for up to 6 hours. This concentration has been estimated to be the minimal effective concentration required to control pain in dogs. CONCLUSION AND RELEVANCE: Oral administration of 2 mg/kg grapiprant in fed and fasted dogs resulted in different pharmacokinetics of the drug, but did not influence the length of time when concentrations in plasma exceeded theoretical effective concentrations. Further studies are necessary to verify these findings using pharmacokinetic-pharmacodynamic studies and in clinical subjects.


Assuntos
Receptores de Prostaglandina E Subtipo EP2/antagonistas & inibidores , Compostos de Sulfonilureia/farmacocinética , Administração Oral , Animais , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Cães , Jejum , Feminino , Meia-Vida , Compostos de Sulfonilureia/administração & dosagem
10.
Vet J ; 202(2): 309-13, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25011711

RESUMO

Flupirtine (FLU) is a non-opioid analgesic drug with no antipyretic or antiphlogistic effects, used in the treatment of a wide range of pain states in human beings. There is a substantial body of evidence on the efficacy of FLU in humans but this is inadequate to recommend its off-label use in veterinary clinical practice. The aim of this study was to evaluate the pharmacokinetic profiles of FLU after IV and PO administration in healthy cats. Six mixed breed adult cats were randomly assigned to two treatment groups using an open, single-dose, two-treatment, two-phase, paired, cross-over design (2 × 2 Latin-square). Group 1 (n = 3) received a single dose of 5 mg/kg of FLU injected IV into the jugular vein. Group 2 (n = 3) received the same dose via PO route. The wash out period was 1 week. Blood samples (1 mL) were collected at assigned times and plasma was then analysed by a validated HPLC method. No adverse effects at the point of injection and no behavioural changes or alterations in health parameters were observed in the animals during or after the study (up to 7 days after the full study). After IV administration, FLU was detectable in plasma up to 36 h. After PO administration, FLU plasma concentrations were lower than those following IV administration, but they were detectable over the same time range. The terminal part of both mean pharmacokinetic curves showed a similar trend of elimination. The oral bioavailability was approximately 40%. This is the first study of FLU in an animal species of veterinary interest and it could pave the way for the use of this active ingredient in the veterinary field.


Assuntos
Aminopiridinas/farmacocinética , Analgésicos/farmacocinética , Gatos/metabolismo , Administração Oral , Animais , Área Sob a Curva , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão/veterinária , Estudos Cross-Over , Feminino , Injeções Intravenosas/veterinária , Masculino
11.
Vet J ; 200(1): 77-81, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24461644

RESUMO

Cimicoxib (CX) is a novel imidazole derivative that is a cyclo-oxygenase (COX)-2 selective non-steroidal anti-inflammatory drug and the latest COX-2 selective inhibitor to be released for veterinary use. Currently there is limited information available on the pharmacokinetic (PK) properties of CX. The aim of the current study was to evaluate the PK features of CX after administration of the recommended dose and after administration of a more variable dose rate in the form of the commercially available tablet. In addition, the effects of food intake on the PK properties were also evaluated. In the first study, five healthy Beagle dogs received 2mg/kg CX via the oral route following a period of fasting. The second study was conducted using six healthy Labrador retriever dogs which each received an 80 mg tablet (approximate dose 1.95-2.5mg/kg) using a crossover design, both in the fasted and fed condition. The plasma concentrations of CX were detected by a validated HPLC method. No adverse effects were observed in any dogs during the experiment. The results from the PK analysis were similar between the studies, regardless of precision of dose and fasted and fed conditions. The mean peak concentration of CX was 0.49 and 0.43 µg/mL under fasted and fed conditions, respectively. The mean half-life was about 3h after all treatments. In addition, simulated multiple dosing data revealed that time over minimal effective concentration was similar after 1.95, 2.0 and 2.5mg/kg dose administrations. These findings suggest that slight variation from the recommended dose should not alter the therapeutic outcome. In addition, CX can be administered to fed dogs without significantly affecting blood levels.


Assuntos
Inibidores de Ciclo-Oxigenase 2/farmacocinética , Cães/metabolismo , Imidazóis/farmacocinética , Sulfonamidas/farmacocinética , Administração Oral , Animais , Área Sob a Curva , Estudos Cross-Over , Relação Dose-Resposta a Droga , Meia-Vida , Masculino , Taxa de Depuração Metabólica , Comprimidos
12.
Vet J ; 198(3): 620-4, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24206632

RESUMO

Drugs that provide effective analgesia in cats are limited. The aim of the present study was to investigate the pharmacokinetics of the novel atypical drug tapentadol (TAP) after intravenous (IV), intramuscular (IM) and subcutaneous (SC) injection in six healthy cats using a 3 × 3 Latin square crossover study design. The dose rate used was 5mg/kg and the concentrations of TAP in plasma were evaluated using high-performance liquid chromatography. Some adverse effects including salivation, agitation and panting, were noted, especially following IV administration. In all three administration groups, TAP concentrations were detectable in plasma for up to 8h. Bioavailability for each route was almost complete, accounting for 94% and 90% after IM and SC administrations, respectively. Drug absorption was faster after IM than SC administration (0.25 h vs. 0.63 h). The half-life of the terminal portion of the plasma concentration curve was not significantly different between the three routes of administrations (2-3h). TAP appears to have some variation in its pharmacokinetic features in cats compared to other animal species. Further studies are needed to evaluate whether TAP would be suitable for use in cats that are experiencing moderate to severe pain, but are sensitive to the adverse effects of commonly prescribed opioids.


Assuntos
Analgésicos Opioides/farmacocinética , Fenóis/farmacocinética , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/sangue , Animais , Gatos , Estudos Cross-Over , Feminino , Injeções Intramusculares/veterinária , Injeções Intravenosas/veterinária , Injeções Subcutâneas/veterinária , Masculino , Fenóis/efeitos adversos , Fenóis/sangue , Tapentadol
13.
Artigo em Inglês | MEDLINE | ID: mdl-23199154

RESUMO

The residue depletion profile of sulfachlorpyrazine was studied in healthy broilers after oral administration of Sulfatyf®, given at a dose of 50 mg sulfachlorpyrazine (SCP) per kg body weight once daily for 3 consecutive days. Twenty-five medicated broilers were slaughtered on the 5th, 10th, 14th and 16th day of post-medication, and muscle, fat with skin, liver and kidney tissues were sampled and analysed using an high-performance liquid chromatography (HPLC) method with satisfactory recovery (74.5% ± 2.9%) and specificity. The estimated values of LOD and LOQ were 18.40 and 55.70 ng ml(-1), respectively. On the 5th and 10th day of post-medication, the concentrations of SCP residue in all samples examined were higher than the corresponding MRLs established by the European Union and the highest SCP concentrations were measured in muscle. A maximum withdrawal time of 14 days was calculated to ensure consumer safety.


Assuntos
Contaminação de Alimentos/análise , Carne/análise , Sulfanilamidas/análise , Administração Oral , Animais , Galinhas , Resíduos de Drogas/análise , Sulfanilamidas/administração & dosagem , Fatores de Tempo , Distribuição Tecidual
14.
J Vet Pharmacol Ther ; 33(4): 389-95, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20646202

RESUMO

Sulfachlorpyrazine (SCP) is currently used to treat coccidian infections in turkeys; however, there is no information available about the withdrawal period necessary for the turkey to be safe for human consumption. A high performance liquid chromatography method with ultraviolet-visible light detection was adapted and validated for the determination of SCP in turkey tissues. The procedure is based on isolation of the (SCP sodium) compound from edible turkey tissues (muscles, liver, kidneys, and fat with skin) with satisfactory recovery (72.80 +/- 1.40) and specificity. The residue depletion of SCP in turkeys was conducted after a dose of 50 mg/kg body weight/day had been administrated orally for 3 days. After treatment has been discontinued residue concentrations were detected in tissues on the 7th day. The highest SCP concentrations were measured in muscles. Based on the results presented in this study, it could be assumed that a withdrawal period of 21 days, before medicated turkeys could be slaughtered, would be sufficient to ensure consumer safety.


Assuntos
Anti-Infecciosos/farmacocinética , Resíduos de Drogas/análise , Sulfanilamidas/farmacocinética , Perus/metabolismo , Administração Oral , Animais , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/análise , Cromatografia Líquida de Alta Pressão/veterinária , Resíduos de Drogas/farmacocinética , Rim/metabolismo , Modelos Lineares , Fígado/metabolismo , Músculos/metabolismo , Distribuição Aleatória , Pele/metabolismo , Gordura Subcutânea/metabolismo , Sulfanilamidas/administração & dosagem , Sulfanilamidas/análise
15.
Pol J Vet Sci ; 13(4): 639-44, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21370741

RESUMO

The aim of this study was to determine the pharmacokinetics of tramadol and its main metabolites after i.v. and i.m. injections. The pharmacokinetic cross-over study was carried out on 6 healthy male beagle dogs. Tramadol was administered by intravenous (i.v.) and intramuscular (i.m.) injection at 4 mg/kg. Tramadol and its main metabolites O-desmethyl-tramadol (M1), N-,N-didesmethyl-tramadol (M2) and N-,O-didesmethyl-tramadol (M5) concentrations were measured in plasma samples by a HPLC coupled with fluorimetric detection; pharmacokinetic evaluations were carried out with a compartmental and non-compartmental model for tramadol and its metabolites, respectively. The bioavailability of the drug, ranging between 84-102% (mean 92%), was within the generally accepted values for a positive bioequivalence decision of (80-125%). After the i.m. injection the mean plasma drug concentration peak was reached after a T(max) of 0.34 h with a C(max) of 2.52 microg/mL. No therapeutic relevant differences were observed between i.m. and i.v. administration. The minimal effective plasma concentration was reached after a few minutes and maintained for about 6-7 h in both administrations. M1 plasma concentration was low and the amounts of the other metabolites produced were analogous in both routes of administration. In conclusion, tramadol was rapidly and almost completely absorbed after i.m. administration and its systemic availability was equivalent to the i.v. injection. The different onset time and duration of action observed were very small and probably therapeutically irrelevant. The i.m. injection is a useful alternative to i.v. injection in the dog.


Assuntos
Analgésicos Opioides/metabolismo , Analgésicos Opioides/farmacocinética , Cães/sangue , Tramadol/metabolismo , Tramadol/farmacocinética , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/sangue , Animais , Disponibilidade Biológica , Estudos Cross-Over , Meia-Vida , Injeções Intramusculares , Injeções Intravenosas , Masculino , Tramadol/administração & dosagem , Tramadol/sangue
17.
N Z Vet J ; 57(3): 146-52, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19521463

RESUMO

AIM: To compare the rectal and I/V administration of tramadol in dogs, to assess both its pharmacokinetic properties and absolute bioavailability. METHODS: After rectal administration via suppositories and I/V injection of tramadol (4 mg/kg), the concentration of tramadol and its main metabolites, O-desmethyl-tramadol (M1), N-desmethyl-tramadol (M2) and N,O-didesmethyl-tramadol (M5), were determined in plasma, using high-performance liquid chromatography (HPLC). A balanced cross-over study was used, involving six male Beagle dogs. RESULTS: Plasma concentrations after rectal and I/V administration were fitted on the basis of mono- and bi-compartmental models, respectively. Following rectal administration tramadol was detected from 5 minutes up to 10 hours, in lesser amounts than M5 and M2, while M1 was detected in negligible amounts. Following I/V administration tramadol was detected up to 10 hours, M2 and M5 were detected at similar concentrations, and M1 was present at low concentrations. The area under the curve (AUC) of the three metabolites did not differ significantly after either route of administration of tramadol. The absolute bioavailability of tramadol via rectal administration was 10 (SD 4)%. CONCLUSIONS: After rectal administration of tramadol suppositories, absorption of the active ingredient was rapid, but its metabolism quickly transformed the parent drug to high levels of M2 and M5. CLINICAL RELEVANCE: In the dog, rectal pharmaceutical formulation of tramadol would have a different pharmacokinetic behaviour than in humans.


Assuntos
Analgésicos Opioides/farmacocinética , Cães/metabolismo , Tramadol/farmacocinética , Administração Retal , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/sangue , Animais , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão/veterinária , Estudos Cross-Over , Meia-Vida , Injeções Intravenosas/veterinária , Masculino , Supositórios , Tramadol/administração & dosagem , Tramadol/análogos & derivados , Tramadol/sangue
18.
Vet Res Commun ; 33(8): 875-85, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19533402

RESUMO

The aim of the present paper was to test the oral administration of oral immediate release capsules of tramadol in dogs, to asses both its pharmacokinetic properties and its urine profile. After capsules administration of tramadol (4 mg/kg), involving eight male Beagle dogs, the concentration of tramadol and its main metabolites, M1, M2 and M5, were determined in plasma and urine using an HPLC method. The plasma concentrations of tramadol and metabolites were fitted on the basis of mono- and non-compartmental models, respectively. Tramadol was detected in plasma from 5 min up to 10 h in lesser amounts than M5 and M2, detected at similar concentrations, while M1 was detected in negligible amounts. In the urine, M5 and M1 showed the highest and smallest amount, respectively; M1 and M5 resulted widely conjugate with glucuronic acid. In conclusion, after oral administration of tramadol immediate release capsules, the absorption of the active ingredient was rapid, but its rapid metabolism quickly transformed the parental drug to high levels of M5 and M2, showing an extensive elimination via the kidney. Hence, in the dog, the oral immediate release pharmaceutical formulation of tramadol would have different pharmacokinetic behaviour than in humans.


Assuntos
Analgésicos Opioides/farmacocinética , Tramadol/farmacocinética , Administração Oral , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/metabolismo , Analgésicos Opioides/urina , Animais , Cães , Masculino , Tramadol/administração & dosagem , Tramadol/metabolismo , Tramadol/urina
19.
J Chromatogr B Analyt Technol Biomed Life Sci ; 877(18-19): 1787-91, 2009 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-19447082

RESUMO

A HPLC method to determine and quantify sulphachloropyrazine residues from broilers and turkeys is reported. This procedure permitted sulphachloropyrazine to be separated from muscle tissue, liver, kidneys and fat with skin after extraction with dichloromethane under slightly acidic conditions. The analytical methodology showed a high specificity and sensitivity and an adequate precision and accuracy with a limit of quantification of 56 ng mL(-1). The peak area showed a linear relationship with a concentration over the range 50-750 ng mL(-1) for sulphachloropyrazine standard solutions. Recovery dates were also satisfactory with values between 69.7 and 77.5%.


Assuntos
Anti-Infecciosos/análise , Cromatografia Líquida de Alta Pressão/métodos , Sulfanilamidas/análise , Animais , Galinhas , Contaminação de Alimentos , Padrões de Referência , Sensibilidade e Especificidade , Distribuição Tecidual , Perus
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