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1.
J Vet Pharmacol Ther ; 38(4): 321-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25376170

RESUMO

Dermorphin is a µ-opioid receptor-binding peptide that causes both central and peripheral effects following intravenous administration to rats, dogs, and humans and has been identified in postrace horse samples. Ten horses were intravenously and/or intramuscularly administered dermorphin (9.3 ± 1.0 µg/kg), and plasma concentration vs. time data were evaluated using compartmental and noncompartmental analyses. Data from intravenous administrations fit a 2-compartment model best with distribution and elimination half-lives (harmonic mean ± pseudo SD) of 0.09 ± 0.02 and 0.76 ± 0.22 h, respectively. Data from intramuscular administrations fit a noncompartmental model best with a terminal elimination half-life of 0.68 ± 0.24 (h). Bioavailability following intramuscular administration was variable (47-100%, n = 3). The percentage of dermorphin excreted in urine was 5.0 (3.7-10.6) %. Excitation accompanied by an increased heart rate followed intravenous administration only and subsided after 5 min. A plot of the mean change in heart rate vs. the plasma concentration of dermorphin fit a hyperbolic equation (simple Emax model), and an EC(50) of 21.1 ± 8.8 ng/mL was calculated. Dermorphin was detected in plasma for 12 h and in urine for 48 or 72 h following intravenous or intramuscular administration, respectively.


Assuntos
Analgésicos Opioides/farmacocinética , Cavalos/sangue , Peptídeos Opioides/farmacocinética , Analgésicos Opioides/sangue , Analgésicos Opioides/farmacologia , Animais , Área Sob a Curva , Feminino , Meia-Vida , Masculino , Peptídeos Opioides/sangue , Peptídeos Opioides/farmacologia , Projetos Piloto
2.
J Vet Pharmacol Ther ; 36(2): 181-91, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22632064

RESUMO

This study investigated and compared the pharmacokinetics of intra-articular (IA) administration of dexamethasone sodium phosphate (DSP) into three equine joints, femoropatellar (IAS), radiocarpal (IAC), and metacarpophalangeal (IAF), and the intramuscular (IM), oral (PO) and intravenous (IV) administrations. No significant differences in the pharmacokinetic estimates between the three joints were observed with the exception of maximum concentration (Cmax ) and time to maximum concentration (Tmax ). Median (range) Cmax for the IAC, IAF, and IAS were 16.9 (14.6-35.4), 23.4 (13.5-73.0), and 46.9 (24.0-72.1) ng/mL, respectively. The Tmax for IAC, IAF, and IAS were 1.0 (0.75-4.0), 0.62 (0.5-1.0), and 0.25 (0.08-0.25) h, respectively. Median (range) elimination half-lives for IA and IM administrations were 3.6 (3.0-4.6) h and 3.4 (2.9-3.7) h, respectively. A 3-compartment model was fitted to the plasma dexamethasone concentration-time curve following the IV administration of DSP; alpha, beta, and gamma half-lives were 0.03 (0.01-0.05), 1.8 (0.34-2.3), and 5.1 (3.3-5.6) h, respectively. Following the PO administration, the median absorption and elimination half-lives were 0.34 (0.29-1.6) and 3.4 (3.1-4.7) h, respectively. Endogenous hydrocortisone plasma concentrations declined from a baseline of 103.8 ± 29.1-3.1 ± 1.3 ng/mL at 20.0 ± 2.7 h following the administration of DSP and recovered to baseline values between 96 and 120 h for IV, IA, and IM administrations and at 72 h for the PO.


Assuntos
Anti-Inflamatórios/farmacocinética , Dexametasona/administração & dosagem , Dexametasona/farmacocinética , Cavalos/metabolismo , Hidrocortisona/sangue , Animais , Anti-Inflamatórios/administração & dosagem , Estudos Cross-Over , Vias de Administração de Medicamentos , Feminino , Cavalos/sangue , Masculino
3.
J Vet Pharmacol Ther ; 35(1): 1-12, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21668837

RESUMO

This review presents a brief historical prospective of the genesis of regulated medication in the US racing industry of which the nonsteroidal anti-inflammatory drug (NSAID) phenylbutazone (PBZ) is the focus. It presents some historical guideposts in the development of the current rules on the use of PBZ by racing jurisdictions in the US. Based on its prevalent use, PBZ remains a focus of attention. The review examines the information presented in a number of different models used to determine the effects and duration of PBZ in the horse. They include naturally occurring lameness and reversible-induced lameness models that directly examine the effects and duration of the administration of various doses of PBZ. The review also examines indirect plasma and tissue models studying the suppression of the release of arachidonic acid-derived mediators of inflammation. The majority of studies suggest an effect of PBZ at 24 h at 4.4 mg/kg. This reflects and substantiates the opinion of many clinical veterinarians, many of whom will not perform a prepurchase lameness examination unless the horse is free of NSAID. This remains the opinion of many regulatory veterinarians responsible for the prerace examination of race horses that they wish to examine a horse without the possibility of an NSAID interfering with the examination and masking possible musculoskeletal conditions. Based on scientific studies, residual effects of PBZ remain at 24 h. The impact of sustained effect on the health and welfare of the horse and its contribution to injuries during competition remains problematic.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Fenilbutazona/uso terapêutico , Animais , Cavalos , Legislação de Medicamentos , Esportes
4.
J Vet Pharmacol Ther ; 35(2): 132-8, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21480929

RESUMO

Pennsylvania (PA) State Racing Commissions regulate the endogenous androgenic steroid, testosterone (TES), in racing intact males (RIM) by quantification of TES in post-race samples. Post-race plasma samples (2209) collected between March 2008 and November 2010 were analyzed for TES, nandrolone (NAN), and other anabolic steroids (ABS). Of the 2209 plasma samples, 2098 had quantifiable TES ≥ 25 pg/mL. Plasma (mean ± SD) concentrations of TES and NAN in RIM were 329.2 ± 266.4 and 96.0 ± 67.8 pg/mL, respectively. Only 64.6% of RIM had quantifiable concentration of NAN, and there was no relationship between TES and NAN. Plasma TES concentrations were significantly (P < 0.0001) higher during the months of April, May, June, July, and August. A significantly higher (P < 0.006) plasma TES was observed in Thoroughbred (TB) (347.6 ± 288.5 pg/mL) vs. that in Standardbred (STB) (315.4 ± 247.7 pg/mL). Plasma concentrations of TES from breeding stallions (BS) were 601.6 ± 356.5 pg/mL. Statistically significant (P < 0.0001) lower plasma concentrations of the two steroids were observed in RIM horses. Based on quantile distribution of TES in the RIM and BS populations, 99.5% were at or below 1546.1 and 1778.0 pg/mL, respectively. Based on this population of RIM, the suggested upper threshold plasma concentration of endogenous TES in horses competing in PA should remain at 2000 pg/mL.


Assuntos
Cavalos/sangue , Cavalos/fisiologia , Nandrolona/sangue , Esportes , Testosterona/sangue , Envelhecimento , Animais , Dopagem Esportivo , Cavalos/genética , Masculino , Valores de Referência , Estações do Ano
5.
J Vet Pharmacol Ther ; 35(5): 478-88, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22233529

RESUMO

Romifidine HCl (romifidine) is an α(2)-agonist commonly used in horses. This study was undertaken to investigate the pharmacokinetics (PK) of romifidine following intravenous (i.v.) administration and describe the relationship between PK parameters and simultaneously recorded pharmacodynamic (PD) parameters. Romifidine (80 µg/kg) was administered by i.v. infusion over 2 min to six adult Thoroughbred horses, and plasma samples were collected and analyzed using liquid chromatography-mass spectrometry. Limit of quantification was <0.1 ng/mL. PD parameters and arterial blood gases were measured for 300 min following romifidine administration. Statistical PD data analysis included mixed-effect modeling. After i.v. administration of romifidine, the plasma concentration-vs.-time curve was best described by a two-compartmental model. Terminal elimination half-life (t(1/2ß) ) was 138.2 (104.6-171.0) min and volumes for central (V(c)) and peripheral (V(2)) compartments were 1.89 (0.93-2.39) and 2.57 (1.71-4.19) L/kg, respectively. Maximum plasma concentration (C(max)) was 51.9 ± 13.1 ng/mL measured at 4 min following commencement of drug administration. Systemic clearance (Cl) was 32.4 (25.5-38.4) mL · min/kg. Romifidine caused a significant reduction in heart rate and cardiac index and an increase in mean arterial pressure (P < 0.05). Sedation score and head height values were significantly different from the baseline values for 120 min (P < 0.05). The decline in cardiovascular and sedative effects correlated with the decline in plasma romifidine concentration (P < 0.05). In conclusion, a highly sensitive analytical technique for the detection of romifidine in equine plasma allowed detailed description of its PK profile. The drug produces long-lasting sedation in horses that corresponds with the long terminal elimination half-life of the drug.


Assuntos
Anestésicos/farmacocinética , Cavalos/sangue , Imidazóis/farmacocinética , Anestésicos/sangue , Animais , Área Sob a Curva , Pressão Sanguínea , Sedação Consciente/veterinária , Feminino , Meia-Vida , Frequência Cardíaca/efeitos dos fármacos , Cavalos/metabolismo , Imidazóis/sangue , Masculino , Respiração/efeitos dos fármacos
6.
J Vet Pharmacol Ther ; 33(5): 485-94, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20840393

RESUMO

Gabapentin is being used in horses although its pharmacokinetic (PK) profile, pharmacodynamic (PD) effects and safety in the equine are not fully investigated. Therefore, we characterized PKs and cardiovascular and behavioral effects of gabapentin in horses. Gabapentin (20 mg/kg) was administered i.v. or p.o. to six horses using a randomized crossover design. Plasma gabapentin concentrations were measured in samples collected 0-48 h postadministration employing liquid chromatography-tandem mass spectrometry. Blood pressures, ECG, and sedation scores were recorded before and for 12 h after gabapentin dosage. Nineteen quantitative measures of behaviors were evaluated. After i.v. gabapentin, the decline in plasma drug concentration over time was best described by a 3-compartment mammillary model. Terminal elimination half-life (t(1/2γ) ) was 8.5 (7.1-13.3) h. After p.o. gabapentin terminal elimination half-life () was 7.7 (6.7-11.9) h. The mean oral bioavailability of gabapentin (± SD) was 16.2 ± 2.8% indicating relatively poor absorption of gabapentin following oral administration in horses. Gabapentin caused a significant increase in sedation scores for 1 h after i.v. dose only (P < 0.05). Among behaviors, drinking frequency was greater and standing rest duration was lower with i.v. gabapentin (P < 0.05). Horses tolerated both i.v. and p.o. gabapentin doses well. There were no significant differences in and . Oral administration yielded much lower plasma concentrations because of low bioavailability.


Assuntos
Aminas/farmacocinética , Ansiolíticos/farmacocinética , Sedação Consciente/veterinária , Ácidos Cicloexanocarboxílicos/farmacocinética , Cavalos , Ácido gama-Aminobutírico/farmacocinética , Aminas/farmacologia , Animais , Ansiolíticos/farmacologia , Ácidos Cicloexanocarboxílicos/farmacologia , Gabapentina , Frequência Cardíaca/efeitos dos fármacos , Masculino , Ácido gama-Aminobutírico/farmacologia
7.
J Clin Invest ; 75(5): 1403-14, 1985 May.
Artigo em Inglês | MEDLINE | ID: mdl-3158672

RESUMO

The purpose of this study was to determine whether cardiac hypertrophy in response to hemodynamic overloading is a primary result of the increased load or is instead a secondary result of such other factors as concurrent sympathetic activation. To make this distinction, four experiments were done; the major experimental result, cardiac hypertrophy, was assessed in terms of ventricular mass and cardiocyte cross-sectional area. In the first experiment, the cat right ventricle was loaded differentially by pressure overloading the ventricle, while unloading a constituent papillary muscle; this model was used to ask whether any endogenous or exogenous substance caused uniform hypertrophy, or whether locally appropriate load responses caused ventricular hypertrophy with papillary muscle atrophy. The latter result obtained, both when each aspect of differential loading was simultaneous and when a previously hypertrophied papillary muscle was unloaded in a pressure overloaded right ventricle. In the second experiment, epicardial denervation and then pressure overloading was used to assess the role of local neurogenic catecholamines in the genesis of hypertrophy. The degree of hypertrophy caused by these procedures was the same as that caused by pressure overloading alone. In the third and fourth experiments, beta-adrenoceptor or alpha-adrenoceptor blockade was produced before and maintained during pressure overloading. The hypertrophic response did not differ in either case from that caused by pressure overloading without adrenoceptor blockade. These experiments demonstrate the following: first, cardiac hypertrophy is a local response to increased load, so that any factor serving as a mediator of this response must be either locally generated or selectively active only in those cardiocytes in which stress and/or strain are increased; second, catecholamines are not that mediator, in that adrenergic activation is neither necessary for nor importantly modifies the cardiac hypertrophic response to an increased hemodynamic load.


Assuntos
Cardiomegalia/fisiopatologia , Hemodinâmica , Receptores Adrenérgicos/fisiologia , Animais , Volume Cardíaco , Cardiomegalia/metabolismo , Gatos , Denervação , Miocárdio/patologia , Norepinefrina/farmacologia , Músculos Papilares/fisiopatologia , Artéria Pulmonar/fisiopatologia , Receptores Adrenérgicos/efeitos dos fármacos
8.
J Pharm Biomed Anal ; 9(1): 33-9, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-2043720

RESUMO

The purpose of this study was two-fold: (1) to develop a simple and sensitive screening procedure for identifying and confirming bromhexine and ambroxol and, (2) to determine the effect of furosemide on the detection of bromhexine, ambroxol, or their metabolites in urine. Female horses (450-550 kg) treated with bromhexine or ambroxol (1 g, p.o.) were used. Urine samples were collected up to 48 h post-drug administration and analysed. Blind samples were used in evaluating the sensitivity of these methods and reproducibility of the results. Bromhexine and ambroxol were extensively metabolized in the horse. These agents and their respective metabolites were identified and confirmed using thin-layer chromatography (TLC) and gas chromatography-mass spectrometry (GC-MS), respectively. Hydroxy-bromhexine and desmethyl-bromhexine were major metabolites found to be unique to bromhexine-treated horses. These metabolites selectively absent from ambroxol-treated horse urine provide a chemical means to distinguish bromhexine from ambroxol administration in horses. These specific metabolites were similarly identified and confirmed in "blind" horse urine samples. The concomitant presence of furosemide (300 mg, i.v.) with bromhexine or ambroxol did not mask the presence of these agents or alter their metabolite profile. By application of the methods described in this study, bromhexine and ambroxol metabolites in horse urine can be easily identified and confirmed.


Assuntos
Ambroxol/urina , Bromoexina/urina , Furosemida/farmacologia , Cavalos/urina , Ambroxol/sangue , Animais , Bromoexina/sangue , Cromatografia em Camada Fina , Feminino
9.
J Anal Toxicol ; 19(5): 307-15, 1995 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7500618

RESUMO

Although urine is the sample of choice for drug tests in racehorses, it is rarely obtained following the sudden death of a racehorse on the track while racing. The purpose of this study was to demonstrate the significance of postmortem tissue samples as an alternative to urine and blood samples in equine drug analysis following the sudden death of a racehorse on the track while participating in a competitive race. Postmortem tissue samples were frozen (-80 degrees C) until analyzed. A 30-40-g portion of each organ was homogenized in a 0.1 M phosphate buffer (pH 7.4), deproteinized, hydrolyzed with beta-glucuronidase, extracted, and screened by thin-layer chromatography and immunoassay. Samples that initially tested positive for drug(s) were then extracted using high-flow, solid-phase extraction cartridges. The eluates were analyzed by gas chromatography-mass spectrometry. The presence of butorphanol in horses HB355 and CD387, pentobarbital in horse HO940, and ergotamine in horses HO940 and CD387 was detected and confirmed. Thus, in the absence of urine and blood samples following sudden death, postmortem tissue samples are equally useful for forensic toxicological investigations of racehorses.


Assuntos
Morte Súbita/patologia , Morte Súbita/veterinária , Dopagem Esportivo , Cavalos/sangue , Cavalos/urina , Animais , Autopsia , Rim/química , Fígado/química , Pulmão/química , Masculino , Miocárdio/química , Baço/química , Distribuição Tecidual
10.
Equine Vet J ; 28(5): 390-6, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8894537

RESUMO

The administration of sodium bicarbonate (NaHCO3) or 'milk shakes' to Standardbred horses before racing is widespread. This study analysed nonrace day (CTL) and prerace venous acid-base values from Standardbred horses racing in Pennsylvania (PA) and New Jersey (NJ). Mean +/- s.d. CTL bicarbonate (HCO3) and base excess (BE) values, for a group of horses stabled during the 1993 racing season at Pocono Downs, Pennsylvania, were 28.6 +/- 1.9 and 2.6 +/- 1.7 mmol/l, respectively. In the same population of horses, mean +/- s.d. values for prerace HCO3- and BE values were 33.1 +/- 2.8 and 7.0 +/- 2.3 mmol/l, respectively, for horses administered frusemide (F) 4 h before race time and 31.5 +/- 2.4 and 5.5 +/- 2.0 mmol/l for the horses not administered frusemide (NF). There were differences (P < 0.05) in pHv, PvCO2, HCO3- and BE values between the CTL and prerace samples. The venous acid-base values of the CTL horses were normally distributed. The prerace acid-base values measured during 1993 were not normally distributed, indicating changes due either to the administration of alkalising substances or other manipulations of the horses on race day. Changes in all acid-base values were observed during the subsequent 1994 racing season with further changes observed when horses were placed in a secured stable 8 h before the race. The criteria used in some racing jurisdictions for disqualifying a horse were the elevations in HCO3-, Na+ and pH. The correlation coefficients (r2) for the least squares regression for HCO3- vs. pH and HCO3- vs. Na+ in prerace venous blood samples were 0.31 and 0.21, respectively, indicating a poor relationship between the 3 acid-base values. To discourage the administration of NaHCO3 to horses before a race, the use of a BE value of > or = 10 mmol/l for NF and > or = 12 mmol/l for F was adopted as a single index for the disqualification of horses from a race. The results of this study indicate that the use of a single index and, in this case BE, has curtailed the prerace administration of NaHCO3 to horses.


Assuntos
Equilíbrio Ácido-Base , Dopagem Esportivo , Cavalos/sangue , Bicarbonato de Sódio/administração & dosagem , Animais , Bicarbonatos/sangue , Cruzamento , Dióxido de Carbono/sangue , Diuréticos/administração & dosagem , Furosemida/administração & dosagem , Concentração de Íons de Hidrogênio , Veias Jugulares , New Jersey , Pennsylvania , Esportes
11.
Equine Vet J ; 32(4): 334-40, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10952383

RESUMO

Seven hundred and eighty-eight Standardbred pacers competing in 8378 races at one racetrack were analysed to determine the effects of the administration of prerace frusemide on racing times (RT). Frusemide was administered i.v. 4 h before the race to pacers diagnosed with exercise-induced pulmonary haemorrhage (EIPH). Of the pacers, starting in the 1997 racing season, 32.5% received prerace frusemide. This study demonstrated that administration of frusemide prior to racing significantly decreased RT. There was an overall significant decrease (P<0.00001) in RT of 0.67 s. The overall RT for horses, geldings, and females, were mean +/- s.e 117.91 +/- 0.06, 118.20 +/- 0.03 and 118.86 +/- 0.04, respectively. RT progressively decreased until age 6 and increased thereafter. Horses, geldings and females ran a mean of 0.46, 0.31 and 0.74 s faster, respectively, with prerace administration of frusemide. This decrease in RT following prerace administration was most pronounced in younger pacers. In this study, a greater percentage of older pacers received prerace frusemide; however, the effect of frusemide on RT was decreasing with age. Prerace venous acid-base screening was performed in 2729 of the pacers competing. Pennsylvania Harness Racing Commission Regulations disqualify Standardbreds from racing with a base excess of over 10 and 12 mmol/l for Standardbreds without and with prerace administration of frusemide. The prerace venous acid-base levels were not significantly related to RT and, for those Standardbreds also sampled following the race, there was no correlation between pre- and postrace acid-base status.


Assuntos
Diuréticos/farmacologia , Furosemida/farmacologia , Cavalos/fisiologia , Corrida , Equilíbrio Ácido-Base , Animais , Feminino , Hemorragia/prevenção & controle , Hemorragia/veterinária , Doenças dos Cavalos/etiologia , Doenças dos Cavalos/prevenção & controle , Masculino , Condicionamento Físico Animal/efeitos adversos , Circulação Pulmonar/efeitos dos fármacos , Esportes
12.
Am J Vet Res ; 54(5): 750-4, 1993 May.
Artigo em Inglês | MEDLINE | ID: mdl-8317768

RESUMO

Concentration of sulfamethazine was measured in plasma and tissues (fat, liver, kidney, spleen, lungs, and skeletal muscle) of pigs given the drug IV and PO. The plasma concentration vs time curve was best described by a 2-compartment model, with a distribution half-life of 0.46 hour and an elimination half-life of 16.9 hours. Bioavailability after oral administration was 85.8 +/- 5.3%. The tissue and plasma sulfamethazine concentration vs time data were used to develop a multi-compartment pharmacokinetic model of sulfamethazine disposition in pigs. Plasma and tissue concentrations of sulfamethazine in pigs were measured at various intervals after multiple oral doses of sulfamethazine, and were compared to concentrations predicted by the model. Model predictions for tissue concentrations of sulfamethazine after addition of the drug to feed (110 micrograms/g of feed for 98 days; 550 micrograms/g for 30 days) were compared to results from other studies. The model accurately predicted the number of days for sulfamethazine concentration to fall below 0.1 micrograms of tissue/g (0.1 ppm, the tolerated concentration) in various tissues.


Assuntos
Sulfametazina/farmacocinética , Suínos/metabolismo , Administração Oral , Animais , Esquema de Medicação , Injeções Intravenosas , Cinética , Modelos Biológicos , Sulfametazina/administração & dosagem , Sulfametazina/sangue , Distribuição Tecidual
13.
Am J Vet Res ; 57(4): 517-21, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8712517

RESUMO

OBJECTIVE: To examine, in horses, the disposition and excretion of the active metabolite 6-methoxy-2-naphthylacetic acid (6MNA) of the nonsteroidal anti-inflammatory prodrug nabumetone. DESIGN: Pharmacokinetic analysis of 6MNA after oral administration of nabumetone and IV administration of 6MNA. PROCEDURE: Using a crossover design, 5 horses were orally administered 3.7 mg of nabumetone/kg of body weight. After a 3-week washout period, 4 horses were administered 2.5 mg of 6MNA/kg, IV. RESULTS: Absorption of nabumetone from the gastrointestinal tract and its metabolism to 6MNA had a median appearance half-life of 0.88 hour. The elimination half-life was 11 hours. Area under the plasma concentration time curve for 6MNA after oral administration of nabumetone was 120.6 mg/h/L. A dose of 2.5 mg/kg of 6MNA administered IV resulted in plasma concentration nearly equivalent to that induced by the orally administered dose. Disposition of 6MNA was modeled as a one-compartment, first-order elimination. The area under the plasma concentration time curve for IV administration of 6MNA was 117.0 mg/h/L, and the specific volume of distribution was 0.247 L/kg. The distribution half-life and the elimination half-life were 0.56 and 7.90 hours, respectively. Percentage of total dose recovered in urine for the 36-hour collection period after the oral and IV administrations was 7.4 and 5.3%, respectively. CONCLUSIONS: Metabolism of nabumetone to 6MNA, as reported in other species, also occurs in horses. There were a number of additional metabolites of nabumetone in urine that could not be fully identified and characterized.


Assuntos
Anti-Inflamatórios não Esteroides/metabolismo , Butanonas/metabolismo , Ácidos Naftalenoacéticos/farmacocinética , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacocinética , Butanonas/administração & dosagem , Butanonas/farmacocinética , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Feminino , Meia-Vida , Cavalos , Absorção Intestinal , Taxa de Depuração Metabólica , Modelos Biológicos , Estrutura Molecular , Nabumetona , Ácidos Naftalenoacéticos/administração & dosagem , Ácidos Naftalenoacéticos/urina
14.
Am J Vet Res ; 56(8): 1075-80, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8533980

RESUMO

Naproxen (+6-methoxy-[alpha-methyl]-2-naphthalene acetic acid) is a nonsteroidal anti-inflammatory drug that is used for the treatment of inflammatory conditions in horses. We developed a model that describes the drug's disposition and renal excretion, including synovial fluid disposition and elimination after IV administration in horses. The plasma disposition, after IV administration of 5 mg/kg of body weight, was described by a two-compartment model; mean +/- SD distribution and elimination half-lives were 1.42 +/- 0.42 and 8.26 +/- 2.56 hours, respectively. Plasma concentration of naproxen after IV administration of 5 mg/kg was 55.3 +/- 13.5 and 0.61 +/- 0.42 mg/L at 5 minutes and 48 hours after its administration, respectively. Steady-state volume of distribution was 0.163 +/- 0.053 L/kg, and area under the plasma concentration time-curve was 372.1 +/- 128.2 mg/h/L. The peak synovial fluid concentration of 12.68 +/- 12.39 mg/L was measured at 6 hours, and decreased to 0.71 +/- 0.38 mg/L at 36 hours after naproxen administration. The decrease of naproxen concentration in synovial fluid paralleled that in plasma. The appearance half-life of naproxen in synovial fluid was 4.64 hours, and the elimination half-life was 6.73 hours. Total body clearance was 0.015 +/- 0.006 L/h/kg. The percentage of plasma protein binding was 97.0 +/- 2.9% at plasma concentrations between 5 and 100 mg/L. This was significantly (P < 0.05) higher than the percentage of binding at plasma concentrations of 0.5, 1, and 500 mg/L, which was 75.2 +/- 11.8%. Most of the drug was excreted as glucuronidated naproxen and unconjugated desmethylnaproxen.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Cavalos/metabolismo , Naproxeno/farmacocinética , Líquido Sinovial/metabolismo , Análise de Variância , Animais , Cromatografia Líquida de Alta Pressão/veterinária , Feminino , Injeções Intravenosas/veterinária , Rim/metabolismo , Modelos Biológicos , Naproxeno/sangue , Naproxeno/urina , Ligação Proteica
15.
Am J Vet Res ; 61(7): 811-5, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10895905

RESUMO

OBJECTIVE: To compare the pharmacokinetics of penicillin G and procaine in racehorses following i.m. administration of penicillin G procaine (PGP) with pharmacokinetics following i.m. administration of penicillin G potassium and procaine hydrochloride (PH). ANIMALS: 6 healthy adult mares. PROCEDURE: Horses were treated with PGP (22,000 units of penicillin G/kg of body weight, i.m.) and with penicillin G potassium (22,000 U/kg, i.m.) and PH (1.55 mg/kg, i.m.). A minimum of 3 weeks was allowed to elapse between drug treatments. Plasma and urine penicillin G and procaine concentrations were measured by use of high-pressure liquid chromatography. RESULTS: Median elimination phase half-lives of penicillin G were 24.7 and 12.9 hours, respectively, after administration of PGP and penicillin G potassium. Plasma penicillin G concentration 24 hours after administration of penicillin G potassium and PH was not significantly different from concentration 24 hours after administration of PGP. Median elimination phase half-life of procaine following administration of PGP (15.6 hours) was significantly longer than value obtained after administration of penicillin G potassium and PH (1 hour). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that i.m. administration of penicillin G potassium will result in plasma penicillin G concentrations for 24 hours after drug administration comparable to those obtained with administration of PGP Clearance of procaine from plasma following administration of penicillin G potassium and PH was rapid, compared with clearance following administration of PGP.


Assuntos
Cavalos/metabolismo , Penicilina G Procaína/farmacocinética , Penicilinas/farmacocinética , Animais , Área Sob a Curva , Cromatografia Líquida de Alta Pressão/veterinária , Feminino , Meia-Vida , Injeções Intramusculares/veterinária , Análise dos Mínimos Quadrados , Penicilina G Procaína/administração & dosagem , Penicilina G Procaína/sangue , Penicilina G Procaína/urina , Penicilinas/administração & dosagem , Penicilinas/sangue , Penicilinas/urina , Estatísticas não Paramétricas
16.
Am J Vet Res ; 62(4): 483-9, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11327452

RESUMO

OBJECTIVE: To determine pharmacokinetics and excretion of phenytoin in horses. ANIMALS: 6 adult horses. PROCEDURE: Using a crossover design, phenytoin was administered (8.8 mg/kg of body weight, IV and PO) to 6 horses to determine bioavailability (F). Phenytoin also was administered orally twice daily for 5 days to those same 6 horses to determine steady-state concentrations and excretion patterns. Blood and urine samples were collected for analysis. RESULTS: Mean (+/- SD) elimination half-life following a single IV or PO administration was 12.6+/-2.8 and 13.9+/-6.3 hours, respectively, and was 11.2+/-4.0 hours following twice-daily administration for 5 days. Values for F ranged from 14.5 to 84.7%. Mean peak plasma concentration (Cmax) following single oral administration was 1.8+/-0.68 microg/ml. Steady-state plasma concentrations following twice-daily administration for 5 days was 4.0+/-1.8 microg/ml. Of the 12.0+/-5.4% of the drug excreted during the 36-hour collection period, 0.78+/-0.39% was the parent drug phenytoin, and 11.2+/-5.3% was 5-(phydroxyphenyl)-5-phenylhydantoin (p-HPPH). Following twice-daily administration for 5 days, phenytoin was quantified in plasma and urine for up to 72 and 96 hours, respectively, and p-HPPH was quantified in urine for up to 144 hours after administration. This excretion pattern was not consistent in all horses. CONCLUSIONS AND CLINICAL RELEVANCE: Variability in F, terminal elimination-phase half-life, and Cmax following single or multiple oral administration of phenytoin was considerable. This variability makes it difficult to predict plasma concentrations in horses after phenytoin administration.


Assuntos
Anticonvulsivantes/farmacocinética , Cavalos/metabolismo , Fenitoína/farmacocinética , Administração Oral , Animais , Anticonvulsivantes/sangue , Anticonvulsivantes/urina , Área Sob a Curva , Disponibilidade Biológica , Estudos Cross-Over , Feminino , Meia-Vida , Injeções Intravenosas/veterinária , Fenitoína/análogos & derivados , Fenitoína/sangue , Fenitoína/urina , Distribuição Aleatória , Estatísticas não Paramétricas
18.
Drug Test Anal ; 2(2): 70-81, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20878889

RESUMO

A non-aqueous capillary electrophoresis-mass spectrometry (NACE-MS) method was developed for simultaneous separation and identification of 12 amphetamine and related compounds in equine plasma. Analytes were recovered from plasma by liquid-liquid extraction using methyl tertiary butyl ether (MTBE). A bare fused-silica capillary was used for separation of the analytes. Addition of sheath liquid to the capillary effluent allowed the detection of the analytes by positive electrospray ionization mass spectrometry using full scan data acquisition. The limit of detection (LOD) for the target analytes was 10-200 ng/mL and that of confirmation (LOC) was 50-1000 ng/mL in equine plasma. Capillary electrophoresis (CE) and mass spectrometry (MS) parameters were optimized for full CE separation and MS detection of the analytes. Separation buffer comprised 25 mM ammonium formate in acetonitrile/methanol (20: 80, v/v) plus 1 M formic acid. Sheath liquid was isopropanol-water-formic acid (50:50:0.5, v/v/v). Samples were hydrodynamically injected and separated at 25 kV. Analytes were electrokinetically separated and mass spectrometrically identified and confirmed. This simple, fast, inexpensive and reproducible method was successfully applied to post race equine plasma and research samples in screening for amphetamine and related drugs.


Assuntos
Anfetamina/sangue , Anfetamina/isolamento & purificação , Cavalos/sangue , Espectrometria de Massas em Tandem/métodos , Anfetamina/química , Animais , Dopagem Esportivo/prevenção & controle , Eletroforese Capilar/métodos , Limite de Detecção , Preparações Farmacêuticas/sangue , Preparações Farmacêuticas/química , Preparações Farmacêuticas/isolamento & purificação
19.
Int J Sports Med ; 30(2): 80-6, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19177313

RESUMO

Darbepoetin alfa (DPO) or Novel Erythropoiesis Erythropoiesis Stimulating Protein (NESP), an analog of recombinant human erythropoietin (rhEPO), is abused as a blood doping agent along with the latter in human sports. This paper describes a new method for unequivocal identification of DPO in human plasma. The analyte was extracted from plasma by immunoaffinity separation with anti-rhEPO antibodies, digested by trypsin followed by PNGase F, and analyzed by liquid chromatography coupled to tandem mass spectrometry. The deglycosylated tryptic peptide, T (9), was employed in DPO identification using liquid chromatographic retention time and major product ions of the T (9) peptide. The limit of detection of this method for DPO was 0.1 ng/mL in plasma, and that of identification was 0.2 ng/mL. This method is definitive and devoid of false positive results, providing "mass fingerprints" for identification of DPO in human plasma samples. Although this method is not applicable to identification of rhEPO in human plasma because it cannot differentiate rhEPO from endogenous EPO, it is the first successful attempt towards establishing a reliable and selective method for definitive identification of exogenously administered EPOs in doping control analyses.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Dopagem Esportivo/prevenção & controle , Eritropoetina/análogos & derivados , Hematínicos/sangue , Detecção do Abuso de Substâncias/métodos , Darbepoetina alfa , Dopagem Esportivo/métodos , Eritropoetina/sangue , Eritropoetina/imunologia , Humanos , Espectrometria de Massas por Ionização por Electrospray
20.
J Vet Pharmacol Ther ; 30(2): 101-8, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17348894

RESUMO

Anabolic steroids (ABS) boldenone (BL; 1.1 mg/kg) and stanozolol (ST; 0.55 mg/kg) were administered i.m. to horses and the plasma samples collected up to 64 days. Anabolic steroids and androgenic steroids (ANS) in plasma were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The limit of detection of all analytes was 25 pg/mL. The median absorption (t1/2 partial differential) and elimination (t1/2e) half-lives for BL were 8.5 h and 123.0 h, respectively, and the area under the plasma concentration-time curve (AUCho) was 274.8 ng.h/mL. The median t1/2e for ST was 82.1 h and the was 700.1 ng.h/mL. Peak mean (X+/-SD) plasma concentrations (Cmax) for BL and ST were 1127.8 and 4118.2 pg/mL, respectively. Quantifiable concentrations of ABS and ANS were found in 61.7% of the 988 plasma samples tested from race tracks. In 17.3% of the plasma samples two or more ABS or ANS were quantifiable. Testosterone (TES) concentrations mean (X+/-SE) in racing and nonracing intact males were 241.3+/-61.3 and 490.4+/-35.1 pg/mL, respectively. TES was not quantified in nonracing geldings and female horses, but was in racing females and geldings. Plasma concentrations of endogenous 19-nortestosterone (nandrolone; NA) from racing and nonracing males were 50.2+/-5.5 and 71.8+/-4.6 pg/mL, respectively.


Assuntos
Anabolizantes/farmacocinética , Androgênios/farmacocinética , Dopagem Esportivo , Cavalos/metabolismo , Estanozolol/farmacocinética , Testosterona/análogos & derivados , Anabolizantes/administração & dosagem , Anabolizantes/sangue , Androgênios/administração & dosagem , Androgênios/sangue , Animais , Área Sob a Curva , Feminino , Injeções Intramusculares/veterinária , Masculino , Condicionamento Físico Animal , Reprodutibilidade dos Testes , Estanozolol/administração & dosagem , Estanozolol/sangue , Testosterona/administração & dosagem , Testosterona/sangue , Testosterona/farmacocinética
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