Pharmacokinetics of boldenone and stanozolol and the results of quantification of anabolic and androgenic steroids in race horses and nonrace horses

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.     

Plasma and synovial fluid endothelin-1 and nitric oxide concentrations in horses with and without joint disease

OBJECTIVE: To compare plasma and synovial fluid endothelin-1 (ET-1) and nitric oxide (NO) concentrations in clinically normal horses and horses with joint disease. ANIMALS: 36 horses with joint disease, and 15 horses without joint disease. PROCEDURE: Horses with joint disease were assigned to 1 of the 3 groups (ie, synovitis, degenerative joint disease [DJD], or joint sepsis groups) on the basis of findings on clinical and radiographic examination and synovial fluid analysis. Endothelin-1 and NO concentrations were measured in plasma from blood samples, collected from the jugular vein and ipsilateral cephalic or saphenous vein of the limb with an affected or unaffected joint, as well as in synovial fluid samples obtained via arthrocentesis from the involved joint. RESULTS: Plasma ET-1 concentrations between affected and unaffected groups were not significantly different. Median concentration and concentration range of ET-1 in synovial fluid obtained from the joint sepsis group (35.830 pg/mL, 7926 to 86.614 pg/mL; n = 7) were significantly greater than values from the synovitis (17.531 pg/mL, 0.01 to 46.908 pg/mL; 18), DJD (22.858 pg/mL, 0.01 to 49.990 pg/mL; 10), and unaffected (10.547 pg/mL, 0.01 to 35.927 pg/mL; 10) groups. Plasma and synovial fluid NO concentrations between affected and unaffected groups were not significantly different. CONCLUSIONS AND CLINICAL RELEVANCE: Endothelin-1 is locally synthesized in the joints of horses with various types of joint disease. Synovial fluid concentrations of ET-1 varied among horses with joint disease, with concentrations significantly higher in the synovial fluid of horses with joint sepsis. These results indicate that ET-1 may play a role in the pathophysiologic mechanism of joint disease in horses.     

Plasma Adrenocorticotropin Concentration in Healthy Horses and in Horses With Clinical Signs of Hyperadrenocorticism

Pituitary adenomas are commonly reported in older horses. The typical clinical signs associated with this condition, also known as equine Cushing's disease (ECD), are related to increased adrenocorticotropin (ACTH) production resulting in hyperadrenocorticism. The primary purpose of this study was to determine whether plasma ACTH concentrations differed between cushingoid and healthy horses. The second objective was to determine the effects of blood sample handling techniques on ACTH concentrations. A commercial human ACTH radioimmunoassay (RIA) was used to quantify equine plasma ACTH. Intra-assay and interassay variations, as well as dilutional parallelism were determined during the RIA validation. Plasma ACTH concentrations were evaluated in a group of healthy equids composed of 18 horses and 9 ponies, and in 22 equids with a clinical diagnosis of hyper adrenocorticism (11 horses and 11 ponies). The mean plasma ACTH concentrations in healthy horses and ponies, (18.68 ± 6.79 pg/mL (mean ± SD) and 8.35 ± 2.92 pg/mL, respectively), were significantly different (P = .009). The mean plasma ACTH concentration in horses and ponies with ECD, (199.18 ± 182.82 pglmL and 206.21 ± 319.56 pg/mL, respectively), were significantly higher than the mean ACTH concentration in the control animals (P < .001). Plasma ACTH concentrations appeared to be a sensitive and specific indicator of ECD in horses and ponies. ACTH concentrations measured in plasma samples kept at room temperature (19°C) as long as 3 hours after blood collection were not statistically different from those of samples kept at 1°C. J Vet Intern Med 1996;10:1–6. Copyright 1996 by the American College of Veterinary Internal Medicine .     

Plasma concentrations of endothelin-like immunoreactivity in healthy horses and horses with naturally acquired gastrointestinal tract disorders

OBJECTIVE: To compare plasma endothelin (ET)- like immunoreactivity between healthy horses and those with naturally acquired gastrointestinal tract disorders. ANIMALS: 29 healthy horses and 142 horses with gastrointestinal tract disorders. PROCEDURE: Blood samples were collected from healthy horses and from horses with gastrointestinal tract disorders prior to treatment. Magnitude and duration of abnormal clinical signs were recorded, and clinical variables were assessed via thorough physical examinations. Plasma concentrations of ET-like immunoreactivity were measured by use of a radioimmunoassay for human endothelin-1, and CBC and plasma biochemical analyses were performed. RESULTS: Plasma ET-like immunoreactivity concentration was significantly increased in horses with gastrointestinal tract disorders, compared with healthy horses. Median plasma concentration of ET-like immunoreactivity was 1.80 pg/ml (range, 1.09 to 3.2 pg/ml) in healthy horses. Plasma ET-like immunoreactivity was greatest in horses with strangulating large-intestinal obstruction (median, 10.02 pg/ml; range, 3.8 to 22.62 pg/ml), peritonitis (9.19 pg/ml; 789 to 25.83 pg/ml), and enterocolitis (8.89 pg/mI; 6.30 to 18.36 pg/ml). Concentration of ET-like immunoreactivity was significantly associated with survival, PCV, and duration of signs of pain. However, correlations for associations with PCV and duration of pain were low. CONCLUSIONS AND CLINICAL RELEVANCE: Horses with gastrointestinal tract disorders have increased plasma concentrations of ET-like immunoreactivity, compared with healthy horses. The greatest values were detected in horses with large-intestinal strangulating obstructions, peritonitis, and enterocolitis. This suggests a potential involvement of ET in the pathogenesis of certain gastrointestinal tract disorders in horses.     

Plasma ionized calcium and parathyroid hormone concentrations in horses after endurance rides

OBJECTIVE: To evaluate changes in plasma ionized calcium (Ca2+) and parathyroid hormone (PTH) concentrations in horses competing in endurance rides. DESIGN: Longitudinal clinical study. ANIMALS: 28 horses. PROCEDURE: Venous blood samples were obtained from horses before and after racing 80 km. Plasma pH and concentrations of Ca2+, PTH, inorganic phosphorus, albumin, lactate, and magnesium were measured. RESULTS: Overall, a significant decrease in mean (+/- SD) plasma Ca2+ concentration (from 6.44 +/- 0.42 to 5.64 +/- 0.42 mg/dl) and a significant increase in plasma PTH concentration (from 49.9 +/- 30.1 to 148.1 +/- 183.0 pg/ml) were found after exercise. Exercise also resulted in significant increases in plasma inorganic phosphorus, albumin, and lactate concentrations. No changes in plasma magnesium concentration or pH were detected after exercise. Plasma PTH concentration was not increased after exercise in 8 horses; in these horses, plasma PTH concentration decreased from 58.2 +/- 26.3 to 27.4 +/- 22.4 pg/ml, although plasma Ca2+ concentration was also decreased. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma Ca2+ concentration was decreased after racing for 80 km, compared with values obtained before racing. In most horses, an increase in plasma PTH concentration that was commensurate with the decrease in plasma Ca2+ was detected; however, some horses had decreased plasma PTH concentrations.     

Digital blood flow and plasma endothelin concentration in clinically endotoxemic horses

OBJECTIVE: To measure plasma endothelin-1 (ET-1) concentrations and digital blood flow in clinically endotoxemic horses. ANIMALS: 36 adult horses that underwent emergency celiotomy for primary gastrointestinal tract disease. PROCEDURE: On days 2 and 5 following surgery, Doppler ultrasonographic digital arterial blood flow measurements were obtained. Hematologic and biochemical analyses were performed, and plasma concentrations of ET-1 and endotoxin (lipopolysaccharide) were determined. A scoring system based on 9 clinical variables was used to assign horses to group B (quartile with greatest cumulative score) or group A (remaining 3 quartiles). Follow-up at 2.5 years was obtained by telephone questionnaire. RESULTS: For all horses on day 2, median (interquartile values) plasma ET-1 concentrations were 1.4 (0.8, 1.7) pg/mL, whereas on day 5, plasma ET-1 concentrations were 1.0 (0.5, 1.6) pg/mL. On day 2, digital blood flow was 0.057 (0.02, 0.07) mL/min in group A horses and 0.035 (0.02, 0.03) mL/min in group B horses. On day 5, plasma ET-1 concentration was significantly (73%) higher in group B horses, compared with group A horses. Thirty of 36 horses were alive at 2.5 years; group A horses were more likely to have survived (odds ratio, 25; 95% confidence interval, 2.4 to 262). Significant associations were found between an increase in digital pulses, hoof wall temperatures, or both and increased digital blood flow (0.14 vs 0.04 mL/min) on day 2 and increased digital arterial diameter (0.32 vs 0.23 cm) on day 5. CONCLUSIONS AND CLINICAL RELEVANCE: Horses with more severe endotoxemia had decreased digital blood flow, increased plasma ET-1 concentrations, and decreased long-term survival.     

Pharmacokinetics and disposition of clenbuterol in the horse

The pharmacokinetics of clenbuterol (CLB) following a single intravenous (i.v.) and oral (p.o.) administration twice daily for 7 days were investigated in thoroughbred horses. The plasma concentrations of CLB following i.v. administration declined mono-exponentially with a median elimination half-life ( t _1/2k) of 9.2 h, area under the time–concentration curve ( AUC ) of 12.4 ng·h/mL, and a zero-time concentration of 1.04 ng/mL. Volume of distribution ( V _d) was 1616.0 mL/kg and plasma clearance ( Cl ) was 120.0 mL/h/kg. The terminal portion of the plasma curve following multiple p.o. administrations also declined mono-exponentially with a median elimination half-life ( t _1/2k) of 12.9 h, a Cl of 94.0 mL/h/kg and V _d of 1574.7 mL/kg. Following the last p.o. administration the baseline plasma concentration was 537.5 ± 268.4 and increased to 1302.6 ± 925.0 pg/mL at 0.25 h, and declined to 18.9 ± 7.4 pg/mL at 96 h. CLB was still quantifiable in urine at 288 h following the last administration (210.0 ± 110 pg/mL). The difference between plasma and urinary concentrations of CLB was 100-fold irrespective of the route of administration. This 100-fold urine/plasma difference should be considered when the presence of CLB in urine is reported by equine forensic laboratories.     

Plasma and urinary concentrations of trimetoquinol by LC‐MS‐MS following intravenous and intra‐tracheal administration to horses with heaves

Trimetoquinol (TMQ) is a very potent and fast acting bronchodilator in horses with heaves. This study assessed the plasma and urinary concentrations of TMQ in horses with heaves following administration via the intravenous (IV, 0.2 μg/kg) and intra‐tracheal (IT, 2 μg/kg) routes. TMQ was administered to six horses affected with heaves (RAO – Recurrent Airway Obstruction, used interchangeably) by the above routes and plasma and urine samples collected and stored at ?20 °C until analyzed. Solid Phase Extraction (SPE) of TMQ was followed by highly sensitive ESI(+)‐LC‐MS‐MS (ElectroSpray Ionization, positive mode – Liquid Chromatography – Mass Spectrometry – Mass Spectrometry); with a Limit of Detection (LOD) estimated at 1 pg/mL. Following IV administration, TMQ plasma levels peaked at 1 min at 707 pg/mL, and at 9 min at 306 pg/mL following IT administration. Our results show that TMQ plasma concentrations decline rapidly following IV administration, which is consistent with the fast onset and short duration of TMQ effect that was observed in our previous studies. On the other hand, IT administration showed a very unique plasma concentration pattern. From a regulatory standpoint, the current available TMQ ELISA kit was also used in an attempt to detect TMQ from the plasma and urine samples. We report that the ELISA kit was unable to detect TMQ from any of the samples generated in these studies.     

Hormonal response to thyrotropin-releasing hormone in healthy horses and in horses with pituitary adenoma

Cortisol, triiodothyronine (T3), thyroxine (T4), insulin, and glucose responses to thyrotropin-releasing hormone (TRH) were evaluated in 12 healthy, mature horses and in 7 horses and 4 ponies with clinical signs of pituitary adenoma (PA). Within 1 hour after TRH administration, the increase in T3 and T4 was similar in healthy horses and animals with PA. Plasma cortisol in the group with PA increased (P less than 0.05) within 0.25 hours after TRH administration, and remained increased for 1.5 hours. In the control group, a significant increase in plasma cortisol concentrations did not develop after TRH administration. Plasma glucose and insulin concentrations were higher in animals with PA than in the healthy horses throughout the experiment (6 hours).     

Pharmacokinetics of intravenous and intramuscular buprenorphine in the horse

The purpose of this study was to determine the pharmacokinetics of buprenorphine following intravenous (i.v.) and intramuscular (i.m.) administration in horses. Six horses received i.v. or i.m. buprenorphine (0.005 mg/kg) in a randomized, crossover design. Plasma samples were collected at predetermined times and horses were monitored for adverse reactions. Buprenorphine concentrations were measured using ultra-performance liquid chromatography with electrospray ionization mass spectrometry. Following i.v. administration, clearance was 7.97±5.16 mL/kg/min, and half-life (T(1/2)) was 3.58 h (harmonic mean). Volume of distribution was 3.01±1.69 L/kg. Following i.m. administration, maximum concentration (C(max)) was 1.74±0.09 ng/mL, which was significantly lower than the highest measured concentration (4.34±1.22 ng/mL) after i.v. administration (P<0.001). Time to C(max) was 0.9±0.69 h and T(1/2) was 4.24 h. Bioavailability was variable (51-88%). Several horses showed signs of excitement. Gut sounds were decreased 10±2.19 and 8.67±1.63 h in the i.v. and i.m. group, respectively. Buprenorphine has a moderate T(1/2) in the horse and was detected at concentrations expected to be therapeutic in other species after i.v. and i.m. administration of 0.005 mg/kg. Signs of excitement and gastrointestinal stasis may be noted.     

Detection and pharmacokinetics of tetrahydrogestrinone in horses

The anti-doping rules of national and international sport federations ban any use of tetrahydrogestrinone (THG) in human as well as in horse sports. Initiated by the THG doping scandals in human sports a method for the detection of 3-keto-4,9,11-triene steroids in horse blood and urine was developed. The method comprises the isolation of the analytes by a combination of solid phase and liquid–liquid extraction after hydrolysis and solvolysis of the steroid conjugates. The concentrations of THG in blood and urine samples were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
A THG excretion study on horses was conducted to verify the method capability for the analysis of postadministration urine samples. In addition, blood samples were collected to allow for determination of the pharmacokinetics of THG in horses. Following the administration of a single oral dose of 25 μg THG per kg bodyweight to 10 horses, samples were collected at appropriate intervals. The plasma levels of THG reached maximal concentrations of 1.5–4.8 ng/mL. Twenty-four hours after the administration plasma levels returned to baseline. In urine, THG was detectable for 36 h. Urinary peak concentrations of total THG ranged from 16 to 206 ng/mL. For the 10 horses tested, the mean plasma clearance of THG was 2250 mL/h/kg and the plasma elimination half-life was 1.9 h.     

Pharmacokinetics and tissue distribution of itraconazole after oral and intravenous administration to horses

OBJECTIVE: To determine the pharmacokinetics of itraconazole after IV or oral administration of a solution or capsules to horses and to examine disposition of itraconazole in the interstitial fluid (ISF), aqueous humor, and polymorphonuclear leukocytes after oral administration of the solution. ANIMALS: 6 healthy horses. PROCEDURE: Horses were administered itraconazole solution (5 mg/kg) by nasogastric tube, and samples of plasma, ISF, aqueous humor, and leukocytes were obtained. Horses were then administered itraconazole capsules (5 mg/kg), and plasma was obtained. Three horses were administered itraconazole (1.5 mg/kg, IV), and plasma samples were obtained. All samples were analyzed by use of high-performance liquid chromatography. Plasma protein binding was determined. Data were analyzed by compartmental and noncompartmental pharmacokinetic methods. RESULTS: Itraconazole reached higher mean +/- SD plasma concentrations after administration of the solution (0.41 +/- 0.13 microg/mL) versus the capsules (0.15 +/- 0.12 microg/mL). Bioavailability after administration of capsules relative to solution was 33.83 +/- 33.08%. Similar to other species, itraconazole has a high volume of distribution (6.3 +/- 0.94 L/kg) and a long half-life (11.3 +/- 2.84 hours). Itraconazole was not detected in the ISF, aqueous humor, or leukocytes. Plasma protein binding was 98.81 +/- 0.17%. CONCLUSIONS AND CLINICAL RELEVANCE: Itraconazole administered orally as a solution had higher, more consistent absorption than orally administered capsules and attained plasma concentrations that are inhibitory against fungi that infect horses. Administration of itraconazole solution (5 mg/kg, PO, q 24 h) is suggested for use in clinical trials to test the efficacy of itraconazole in horses.     

Circannual variation in plasma adrenocorticotropic hormone concentrations in the UK in normal horses and ponies, and those with pituitary pars intermedia dysfunction

Reasons for performing study: Pituitary pars intermedia dysfunction (PPID) is a common endocrinopathy, frequently diagnosed via plasma adrenocorticotropic hormone (ACTH) concentrations. Seasonal variation in plasma ACTH concentrations has been described in normal horses prompting caution in diagnosing PPID at certain times of the year. The aims of this study were to determine appropriate reference intervals for equine plasma ACTH throughout the year; and to examine the circannual variation of plasma ACTH concentrations in PPID cases. Hypothesis: Plasma ACTH can be used as a test for PPID throughout the year with the use of appropriate reference intervals. Methods: Data for reference interval calculations were obtained from samples collected from inpatients of Liphook Equine Hospital (non‐PPID group, n = 156). Data from PPID cases (n = 941) were obtained from samples submitted to the Liphook Equine Hospital Laboratory from horses with a clinical suspicion of PPID found to have plasma ACTH concentrations greater than our upper reference interval for that time of year. Results: Upper limits for reference interval of plasma ACTH were 29 pg/ml between November and July and 47 pg/ml between August and October. Circannual variation in plasma ACTH occurred in both non‐PPID and PPID horses with the highest ACTH concentrations found between August and October in both groups (P<0.0001). The greatest difference between the 2 populations also occurred between August and October. Conclusions: Plasma ACTH can be used for the diagnosis and monitoring of PPID throughout the year with the use of appropriate reference intervals. These findings demonstrate an increase in pituitary gland secretory activity during the late summer and autumn in both normal and PPID cases.     

Plasma and pulmonary disposition of ceftiofur and its metabolites after intramuscular administration of ceftiofur crystalline free acid in weanling foals

The objectives of this study were to determine the plasma and pulmonary disposition of ceftiofur crystalline free acid (CCFA) in weanling foals and to compare the plasma pharmacokinetic profile of weanling foals to that of adult horses. A single dose of CCFA was administered intramuscularly to six weanling foals and six adult horses at a dose of 6.6 mg/kg of body weight. Concentrations of desfuroylceftiofur acetamide (DCA) were determined in the plasma of all animals, and in pulmonary epithelial lining fluid (PELF) and bronchoalveolar lavage (BAL) cells of foals. After intramuscular (IM) administration to foals, median time to maximum plasma and PELF concentrations was 24 h (12-48 h). Mean (± SD) peak DCA concentration in plasma (1.44 ± 0.46 μg/mL) was significantly higher than that in PELF (0.46 ± 0.03 μg/mL) and BAL cells (0.024 ± 0.011 μg/mL). Time above the therapeutic target of 0.2 μg/mL was significantly longer in plasma (185 ± 20 h) than in PELF (107 ± 31 h). The concentration of DCA in BAL cells did not reach the therapeutic level. Adult horses had significantly lower peak plasma concentrations and area under the curve compared to foals. Based on the results of this study, CCFA administered IM at 6.6 mg/kg in weanling foals provided plasma and PELF concentrations above the therapeutic target of 0.2 μg/mL for at least 4 days and would be expected to be an effective treatment for pneumonia caused by Streptococcus equi subsp. zooepidemicus at doses similar to the adult label.     

Plasma leptin, ghrelin and adiponectin concentrations in young fit racehorses versus mature unfit standardbreds

Concentrations of hormones related to energy homeostasis may differ between populations with varied body compositions, acting as signals to increase or decrease energy intake and/or expenditure. How these parameters correlate with body composition in horses and how they vary in fit (F) versus unfit (UF) Standardbred racehorses is unclear. The purpose of this study was to test the hypothesis that plasma concentrations of glucose (GLU), insulin (INS), cortisol (CORT), ghrelin (GHRL), adiponectin (ADIP) and leptin (LEP) would be correlated with body composition and differ in fit (F) versus unfit (UF) horses. Fasting plasma samples were taken from 12 unfit (11 +/- 2 years, 521 +/- 77 kg; mean +/- SD) and 34 fit (4 +/- 2 years, 475 +/- 83 kg) Standardbred horses. GHRL, LEP, ADIP, INS and CORT concentrations were measured using radioimmunoassay. GLU concentration was measured using colorometric kits. Body composition data included body weight, body condition score (BCS), and percent fat (%fat) calculated using rump fat thickness measured ultrasonically and the Westervelt equation. Data were analyzed using Pearson Product moment and Student's t tests. There were no differences (P>0.05) between F and UF horses for the plasma concentrations of CORT (69 +/- 14 versus 76 +/- 23 microg/dL), INS (7.2 +/- 3.5 versus 7.1 +/- 1.8 microIU/mL) or GLU (90 +/- 6 versus 86 +/- 7 mg/dL). Plasma GHRL and ADIP concentrations were greater (P<0.05) in F versus UF horses (54 +/- 27 versus 33 +/- 17 pg/mL and 1820 +/- 276 versus 1333 +/- 249 ng/mL, respectively), while plasma LEP was lower in F versus UF (1.0 +/- 0.6 versus 4.4 +/- 2.4 ng/mL, P<0.001). BCS and %fat were lower in F versus UF horses (4.8 +/- 0.3 versus 6.7 +/- 0.5 and 11.9 +/- 1.6 versus 15.4 +/- 2.5%, respectively), with no correlation between %fat and GHRL (-0.12, P>0.05), although there was a positive correlation between %fat and LEP (+0.72, P<0.05), and a negative correlation between %fat and ADIP (-0.40, P<0.05). The data show that in comparing fit and unfit horses, there are variations in body composition as well as concurrent and substantial differences in the concentrations of hormones, cytokines, and other parameters related to the control of appetite and feed intake.     

A history of the prevalence and control of contagious bovine pleuropneumonia in China

Atrial natriuretic peptide (ANP) is a cardiovascular biomarker that might be useful in assessing the severity of cardiac disease in horses. Plasma ANP concentrations (Cp(ANP)) were compared between horses with heart disease but normal chamber size and function (Group A; n=6), horses with heart disease associated with left atrial (LA) enlargement, LA dysfunction, and/or left ventricular (LV) enlargement (Group B; n=5), and horses with no clinically apparent cardiovascular disease (Group C; n=13). The median (min-max) for Cp(ANP) was significantly higher in Group B (53.5 (36.0-70.7) pg/mL), compared to Group A (12.5 (6.3-19.8) pg/mL) and Group C (13.4 (7.2-34.0) pg/mL). Backwards stepwise multiple linear regression showed that Cp(ANP) in horses with heart disease was related to LA dimensions, but not to LV size, LA function, and LV function. The results indicated that Cp(ANP) in horses might be useful in detecting LA enlargement and that Cp(ANP) could be related to the severity of cardiac disease. Larger prospective studies are necessary to confirm these results.     

Plasma atrial natriuretic peptide concentration in warmblood horses with heart valve regurgitations

ObjectivesThis study measured plasma atrial natriuretic peptide (ANP) concentration in horses with heart valve regurgitations (HVR) with and without atrial and ventricular dilatation.BackgroundIn humans and small animals, plasma ANP concentration is increased in heart disease and correlates with the severity of clinical signs and heart enlargement.Animals, materials and methodsTen healthy horses (control) and 36 horses with HVR were evaluated by auscultation, electrocardiography, echocardiography, and determination of plasma ANP.ResultsControl horses demonstrated mean plasma ANP concentration of 21 ± 5.4 pg/mL. Of the 36 horses with HVR, 17 horses possessed normal echocardiographic heart size (group 1), 10 horses had a left atrial dilatation (group 2) and 9 horses had both left atrial and ventricular dilatation (group 3). Mean plasma ANP concentration of groups 1, 2 and 3 was 20.1 ± 5.6 pg/mL, 22.9 ± 11.0 pg/mL and 27.6 ± 17.4 pg/mL, respectively. The plasma ANP concentrations of HVR and control horses were not significantly different. The highest ANP concentrations were observed in horses with atrial and ventricular dilatation. No correlation between left atrial or ventricular size, weight, or sex and the plasma ANP concentration was found.ConclusionsNo significant differences in plasma ANP concentration was observed between groups. Further study, especially in horses with clinical signs of heart failure is needed.     

Pharmacokinetics of pioglitazone after multiple oral dose administration in horses

Pioglitazone is a thiazolidinedione class of antidiabetic agent with proven efficacy in increasing insulin sensitivity in humans with noninsulin-dependent diabetes mellitus, a syndrome of insulin resistance sharing similarities with equine metabolic syndrome. The purpose of this study was to determine the pharmacokinetics of pioglitazone in adult horses following multiple oral dose administration. Pioglitazone hydrochloride (1 mg/kg) was administered orally for 11 doses at 24-h intervals, and plasma samples were collected. Initially, a pilot study was performed using one horse; and thereafter the drug was administered to six horses. Samples were analyzed by liquid chromatography with tandem mass spectrometry, and pharmacokinetic parameters were calculated using noncompartmental modeling. The maximum plasma concentration was 509.1 ± 413.5 ng/mL achieved at 1.88 ± 1.39 h following oral administration of the first dose, and 448.1 ± 303.5 ng/mL achieved at 2.83 ± 1.81 h (mean ± SD) following the eleventh dose. Apparent elimination half-life was 9.94 ± 4.57 and 9.63 ± 5.33 h after the first and eleventh dose, respectively. This study showed that in healthy horses, pioglitazone administered at a daily oral dose of 1 mg/kg results in plasma concentrations and total drug exposure approximating, but slightly below, those considered therapeutic in humans.     

Pharmacokinetic and pharmacodynamic properties of pergolide mesylate following long‐term administration to horses with pituitary pars intermedia dysfunction

The objective of this study was to gain an understanding of the pharmacokinetic and pharmacodynamic properties of pergolide in horses with PPID after of long‐term oral administration. Six horses with confirmed PPID were treated with pergolide (Prascend^®) at 1 mg/horse po q24 h for 2 months, followed by 2 mg/horse po q24 h for 4 months. Following the last dose, plasma samples were collected for measurement of pergolide using an LC/MS/MS method and ACTH measurement using a chemiluminescent immunoassay. Noncompartmental and compartmental pharmacokinetic analyses were performed, as well as pharmacodynamic assessment of the effect of plasma pergolide concentrations on plasma ACTH concentrations. Pergolide effectively decreased plasma ACTH concentration in aged horses with PPID, with similar pharmacokinetic properties as reported in young horses, including an approximate terminal half‐life of 24 h. Plasma ACTH concentration increased by 50% in 3/6 horses at 2 days and 6/6 horses 10 days after discontinuing drug administration. Pergolide was quantified in all horses at 2 days and in none at 10 days after last dose. In summary, after discontinuing pergolide treatment, plasma ACTH concentration increased while pergolide was still quantifiable in some horses. Once‐daily dosing of pergolide is likely appropriate in most horses with PPID for regulating the plasma ACTH concentration.     

Pharmacokinetics of intra‐articular betamethasone sodium phosphate and betamethasone acetate and endogenous hydrocortisone suppression in exercising horses

To the date, no reports exist of the pharmacokinetics (PK) of betamethasone (BTM) sodium phosphate and betamethasone acetate administered intra‐articular (IA) into multiple joints in exercising horses. The purpose of the study was to determine the PK of BTM and HYD concentrations in plasma and urine after IA administration of a total of 30 mg BTM. Eight 4 years old Thoroughbred mares were exercised on a treadmill and BTM was administered IA. Plasma and urine BTM and HYD were determined via high performance liquid chromatography spectrometry for 6 weeks. Concentration‐time profiles of BTM and HYD in plasma and urine were used to generate PK estimates for non‐compartmental analyses and comparisons among times and HYD concentrations. BTM in plasma had greater T_max (T_max 0.8 h) vs. urine (T_max 7.1 h). Urine BTM concentration (ng/mL) and amount (AUC_last; h × ng/mL) were greater than plasma. HYD was suppressed for at least 3 days (<1 ng/mL) for all horses. The time of last quantifiable concentration of BTM (T_last; hour) was not significantly different in plasma than urine. Use of highly sensitive HPLC‐MS/MS assays enabled early detection and prolonged and consistent determination of BTM in plasma and urine.