Pharmacokinetics of ganciclovir and valganciclovir in the adult horse

Equine herpes myeloencephalopathy, resulting from equine herpes virus type 1 (EHV‐1) infection, is associated with substantial morbidity and mortality in the horse. As compared to other antiviral drugs, such as acyclovir, ganciclovir has enhanced potency against EHV‐1. This study investigated the pharmacokinetics of ganciclovir and its oral prodrug, valganciclovir, in six adult horses in a randomized cross‐over design. Ganciclovir sodium was administered intravenously as a slow bolus at a dose of 2.5 mg/kg, and valganciclovir was administered orally at a dose of 1800 mg per horse. Intravenously administered ganciclovir disposition was best described by a three‐compartment model with a prolonged terminal half‐life of 72 ± 9 h. Following the oral administration of valganciclovir, the mean observed maximum serum ganciclovir concentration was 0.58 ± 0.37 μg/mL, and bioavailability of ganciclovir from oral valganciclovir was 41 ± 20%. Superposition predicted that oral dosing of 1800‐mg valganciclovir two times daily would fail to produce and maintain effective plasma concentrations of ganciclovir. However, superposition suggested that i.v. administration of ganciclovir at 2.5 mg/kg every 8 h for 24 h followed by maintenance dosing of 2.5 mg/kg every 12 h would maintain effective ganciclovir serum concentrations in most horses throughout the dosing interval.     

Pharmacokinetics of procaterol in thoroughbred horses

Procaterol (PCR) is a beta‐2‐adrenergic bronchodilator widely used in Japanese racehorses for treating lower respiratory disease. The pharmacokinetics of PCR following single intravenous (0.5 μg/kg) and oral (2.0 μg/kg) administrations were investigated in six thoroughbred horses. Plasma and urine concentrations of PCR were measured using liquid chromatography–mass spectrometry. Plasma PCR concentration following intravenous administration showed a biphasic elimination pattern. The systemic clearance was 0.47 ± 0.16 L/h/kg, the steady‐state volume of the distribution was 1.21 ± 0.23 L/kg, and the elimination half‐life was 2.85 ± 1.35 h. Heart rate rapidly increased after intravenous administration and gradually decreased thereafter. A strong correlation between heart rate and plasma concentration of PCR was observed. Plasma concentrations of PCR after oral administration were not quantifiable in all horses. Urine concentrations of PCR following intravenous and oral administrations were quantified in all horses until 32 h after administration. Urine PCR concentrations were not significantly different on and after 24 h between intravenous and oral administrations. These results suggest that the bioavailability of orally administrated PCR in horses is very poor, and the drug was eliminated from the body slowly based on urinary concentrations. This report is the first study to demonstrate the pharmacokinetic character of PCR in thoroughbred horses.     

Development of intraosseous infusion of the distal phalanx to access the foot lamellar circulation in the standing,conscious horse

Intraosseous (IO) infusion of the distal phalanx (IOIDP) as a delivery route targeting hoof lamellar tissue of standing, conscious horses was evaluated. Following sedation and regional nerve blockade in six Standardbred horses, a microdialysis (MD) probe was implanted into the hoof lamellar tissue of one forelimb. A purpose designed cannulated bone screw was introduced into the body of the distal phalanx, approximately 6 cm from the MD probe. Gentamicin solution (25 mg/mL) was infused at 20 μL/min through the bone screw for 2 h without the application of a tourniquet. MD and blood samples were collected at regular intervals and analysed for gentamicin concentrations.Gentamicin was present in lamellar tissue at much higher concentrations than peripheral serum. The mean concentration of gentamicin was 24.4, 20.5 and 4.4 μg/mL in extracellular fluid (ECF) and 0.28, 0.5 and 0.32 μg/mL in serum samples collected 60, 120 and 150 min after IOIDP was started, respectively. A clinically safe and efficacious IO drug delivery to the hoof lamellar tissue of standing, conscious horse was developed.     

Plasma concentration‐dependent suppression of endogenous hydrocortisone in the horse after intramuscular administration of dexamethasone‐21‐isonicotinate

Detection times and screening limits (SL) are methods used to ensure that the performance of horses in equestrian sports is not altered by drugs. Drug concentration–response relationship and knowledge of concentration–time profiles in both plasma and urine are required. In this study, dexamethasone plasma and urine concentration–time profiles were investigated. Endogenous hydrocortisone plasma concentrations and their relationship to dexamethasone plasma concentrations were also explored. A single dose of dexamethasone‐21‐isonicotinate suspension (0.03 mg/kg) was administered intramuscularly to six horses. Plasma was analysed for dexamethasone and hydrocortisone and urine for dexamethasone, using UPLC‐MS/MS. Dexamethasone was quantifiable in plasma for 8.3 ± 2.9 days (LLOQ: 0.025 μg/L) and in urine for 9.8 ± 3.1 days (LLOQ: 0.15 μg/L). Maximum observed dexamethasone concentration in plasma was 0.61 ± 0.12 μg/L and in urine 4.2 ± 0.9 μg/L. Terminal plasma half‐life was 38.7 ± 19 h. Hydrocortisone was significantly suppressed for 140 h. The plasma half‐life of hydrocortisone was 2.7 ± 1.3 h. Dexamethasone potency, efficacy and sigmoidicity factor for hydrocortisone suppression were 0.06 ± 0.04 μg/L, 0.95 ± 0.04 and 6.2 ± 4.6, respectively. Hydrocortisone suppression relates to the plasma concentration of dexamethasone. Thus, determination of irrelevant plasma concentrations and SL is possible. Future research will determine whether hydrocortisone suppression can be used as a biomarker of the clinical effect of dexamethasone.     

The Use of Pneumatic Impact Lithotripsy in a Laparoscopic Retrieval Pouch for Removal of Large Cystoliths in Two Female Horses

Two mares, aged 15 and 21 years, were examined because of urinary incontinence, intermittent hematuria, and urine scalding. On admission of both horses, physical parameters were within normal limits and urine scalding of the skin at the ventral perineum was noted. Transrectal palpation and cystoscopy revealed a large type I cystolith (>10 cm) with associated hyperemia and focal ulceration of the bladder mucosa. In horse 1, hemogram, serum biochemical analysis, and renal ultrasound were not performed because of owner finances. In horse 2, results from hematological and serum biochemical analysis were unremarkable and renal ultrasonography did not reveal any abnormalities. Pneumatic impact lithotripsy in a laparoscopic retrieval pouch was performed under cystoscopic guidance after caudal epidural anesthesia, with the horses standing and under sedation. A laparoscopic retrieval device was passed alongside a flexible endoscope into the urinary bladder and the cystolith was manipulated into the pouch. A customized single stainless-steel rod scaler attached to an air compressor was used for fragmentation of the cystolith contained within the retrieval pouch. Lithotripsy time was 42 minutes for horse 1 and 31 minutes for horse 2. Both horses were released from hospital the day of surgery. Both horses were continent and voided normal streams of urine for the duration of the follow-up periods of 27 and 19 months for horse 1 and horse 2, respectively. Pneumatic impact lithotripsy in a laparoscopic retrieval pouch provided a time-efficient and minimally invasive surgical treatment option for removal of large cystoliths in mares.     

Pharmacokinetics of chloramphenicol base in horses and comparison to compounded formulations

Chloramphenicol is commonly used in horses; however, there are no studies evaluating the pharmacokinetics of veterinary canine‐approved tablets. Studies using different formulations and earlier analytical techniques led to concerns over low bioavailability in horses. Safety concerns about human health have led many veterinarians to prescribe compounded formulations that are already in suspension or paste form. The objective of this study was to evaluate the pharmacokinetics of approved chloramphenicol tablets in horses, along with compounded preparations. The hypothesis was that chloramphenicol has low absorption and a short half‐life in horses leading to low serum concentrations and that compounded preparations have lower relative bioavailability. Seven horses were administered chloramphenicol tablets (50 mg/kg orally). In a crossover design, they were administered two compounded preparations to compare all three formulations at the same dose (50 mg/kg). C_max was 5.25 ± 4.07 μg/ml at 4.89 hr, 4.96 ± 3.31 μg/ml at 4.14 hr, and 3.84 ± 2.96 μg/ml at 4.39 hr for the tablets, paste, and suspension, respectively. Elimination half‐life was 2.65 ± 0.75, 3.47 ± 1.47, and 4.36 ± 4.54 hr for tablets, paste, and suspension, respectively. The AUC_0→∞ was 17.93 ± 7.69, 16.25 ± 1.85, and 14.00 ± 5.47 hr*μg/ml for the tablets, compounded paste, and compounded suspension, respectively. Relative bioavailability of compounded suspension and paste was 78.1% and 90.6%. C_max after administration of all formulations did not reach the recommended MIC target of 8 μg/ml set by the Clinical Laboratory Standards Institute (CLSI) for most bacteria. Multidose studies are warranted, but the low serum concentrations suggest that bacteria with MIC values lower than CLSI recommendations should be targeted in adult horses.     

The pharmacokinetics and antiparasitic activity of ivermectin in Hutsul and Toric horses

The aim of this study was to compare the pharmacokinetics of ivermectin and its antiparasitic activity in two horse breeds. Eight Hutsul and 14 Toric horses were administered ivermectin orally at a dose of 0.2 mg/kg body weight. Blood samples were collected for 96 hr, and faecal samples were collected one day before and on days 14 and 21 after drug administration. Ivermectin concentrations in plasma samples were determined by high‐performance liquid chromatography. Ivermectin concentration was significantly higher in Toric than in Hutsul horses 90 min after ivermectin administration and was maintained at higher level for up to 96 hr. The area under the concentration versus the time curve from 0 to the last sampling point (AUC_0→t) and the maximum plasma concentration (C_max) were significantly higher in Toric than in Hutsul horses (1792.09 ± 246.22 μg × hr/L vs. 716.99 ± 255.81 μg × hr/L and 62.72 ± 17.97 ng/ml vs. 35.34 ± 13.61 ng/ml, respectively). No parasitic eggs were found in the faecal samples collected from both groups of horses on days 14 and 21 after drug administration. The obtained results indicate that although the pharmacokinetics of ivermectin may differ significantly between horse breeds, these differences do not affect the effectiveness of therapy.     

Effect of a pelleted supplement fed during and after omeprazole treatment on nonglandular gastric ulcer scores and gastric juice pH in horses

Gastric ulcers are common in horses. The purpose of this study was to test the effect of a commercially available supplement, SmartGut^® Ultra pellets (SmGU) on gastric ulcer scores and gastric juice pH after omeprazole treatment in stall‐confined horses. Eight Thoroughbred horses were studied in a 2‐period, 2‐treatment crossover design, where the SmGU (40 g, twice daily) was mixed in grain feed. Horses were stall‐confined and treated with the supplement or control for 6 weeks, consisting of 2 weeks (Days 1–14) omeprazole treatment, 2 weeks (Days 14–28) following discontinuation of omeprazole treatment, one week (Days 28–35) alternating feed deprivation to induce or worsen existing ulcers and a one week (Days 35–42) recovery period. Gastroscopy was performed and gastric juice pH measured on Days 0, 14, 28, 35 and 42. Gastric ulcer lesion number (NGN) and severity (NGS) scores were assigned to each horse by an investigator (F.M.A.) masked to treatment. On Day 0 before treatment, mean NGN and NGS scores and gastric juice pH were not different (P>0.05) between treatment groups. By Day 14, mean NGN and NGS scores decreased (P<0.05) in both treatment groups. By Days 28 and 35, mean NGN score significantly increased in the untreated control horses but not the SmGU‐treated horses. By Day 42, mean NGN and NGS scores were not different in either group and were significantly lower than Day 0. Mean gastric juice pH was higher in both groups on Day 14 as a result of omeprazole treatment when compared with other days. SmartGut^® Ultra supplement added to the feed prevented the worsening of gastric ulcer number 2 weeks after omeprazole treatment, without altering the gastric juice pH. Supplementation with SmGU might aid in protection of the nonglandular stomach from recurrence of ulcers after omeprazole treatment in stall‐confined horses undergoing intermittent feeding.     

Causes of pleural effusions in horses resident in the UK

Pleural effusions (PE) reportedly occur most commonly secondary to bacterial pneumonia with neoplastic effusions contributing a minority of cases. The majority of reports originate from the USA and Australia, where long distance transport of horses, a recognised risk factor, may occur more frequently than in the UK. Anecdotally, a greater proportion of horses with PE are diagnosed with neoplasia in the UK than has been reported. The aim of this retrospective study was to describe the causes of PE in horses in the UK, and to identify markers that can help differentiate between septic and neoplastic causes of PE. Medical records from 4 equine hospitals in the UK were searched for horses diagnosed with PE. Information recorded included case background, admission physical examination and biochemical findings, and characteristics of the effusion (volume, cell count, total protein [TP] concentration). A total of 69 horses were identified, with 26 (38%) diagnosed with a neoplastic effusion. The remainder were categorised as septic, including 14/43 (32.5%) that had a history of international transport. Horses with septic effusions were significantly younger (8 vs. 13 years; P = 0.001) and had significantly smaller volumes of pleural fluid drained at admission (9.8 l vs. 32.2 l; P<0.001). Horses with septic PE had a significantly higher rectal temperature (38.6°C vs. 38.2°C; P = 0.03), fibrinogen concentration (7.8 g/l vs. 5.3 g/l; P = 0.01) and serum amyloid A concentration (230 mg/l vs. 59 mg/l; P = 0.02) than those with neoplastic effusions. Significantly higher pleural fluid cell count and TP concentration were identified in horses with septic PE (63.9 × 10⁹/l vs. 8.6 × 10⁹/l; P<0.001; 57.5 g/l vs. 35.9 g/l; P = 0.04). These results suggest that in the UK, neoplastic effusions account for a greater proportion of PE than previously reported. A large volume of PE in an older horse with a low cell count and relatively low TP concentration should increase the index of suspicion of neoplasia.     

Resistant cutoff values and optimal scheme establishments for florfenicol against Escherichia coli with PK‐PD modeling analysis in pigs

Florfenicol, a structural analog of thiamphenicol, has broad‐spectrum antibacterial activity against gram‐negative and gram‐positive bacteria. This study was conducted to investigate the epidemiological, pharmacokinetic–pharmacodynamic cutoff, and the optimal scheme of florfenicol against Escherichia coli (E. coli) with PK‐PD integrated model in the target infectious tissue. 220 E. coli strains were selected to detect the susceptibility to florfenicol, and a virulent strain P190, whose minimum inhibitory concentration (MIC) was similar to the MIC₅₀ (8 μg/ml), was analyzed for PD study in LB and ileum fluid. The MIC of P190 in the ileum fluid was 0.25 times lower than LB. The ratios of MBC/MIC were four both in the ileum and LB. The characteristics of time‐killing curves also coincided with the MBC determination. The recommended dosages (30 mg/kg·body weight) were orally administrated in healthy pigs, and both plasma and ileum fluid were collected for PK study. The main pharmacokinetics (PK) parameters including AUC_24 hr, AUC_0–∞, T_max, T_1/2, C_max, CL_b, and K_e were 49.83, 52.33 μg*h/ml, 1.32, 10.58 hr, 9.12 μg/ml, 0.50 L/hr*kg, 0.24 hr^?1 and 134.45, 138.71 μg*hr/ml, 2.05, 13.01 hr, 16.57 μg/ml, 0.18 L/hr*kg, 0.14 hr^?1 in the serum and ileum fluid, respectively. The optimum doses for bacteriostatic, bactericidal, and elimination activities were 29.81, 34.88, and 36.52 mg/kg for 50% target and 33.95, 39.79, and 42.55 mg/kg for 90% target, respectively. The final sensitive breakpoint was defined as 16 μg/ml. The current data presented provide the optimal regimens (39.79 mg/kg) and susceptible breakpoint (16 μg/ml) for clinical use, but these predicted data should be validated in the clinical practice.     

Aortic rupture causing cardiac tamponade in a 24‐day‐old Friesian colt with concurrent colonic Chlamydiosis and Balantidiasis

A 24‐day‐old Friesian colt died suddenly and a physical examination the morning the foal died showed no abnormalities and serum IgG levels >8.0 g/l. Necropsy examination revealed haemopericardium and a 2 cm transverse tear at the root of the aorta. The foal was also found to have Chlamydophila spp. in the epithelium and Balantidium coli on the mucosal surface of the large colon. An aortic rupture is a novel finding in a foal, colonic Chlamydiosis has not been previously reported in horses and Balantidium coli has not been reported in equids in North America.     

Evaluation of plasma concentration after intravenous and intramuscular penicillin administration over 24 hr in healthy adult horses

Penicillin is administered intravenously (IV) or intramuscularly (IM) to horses for the prevention and treatment of infections, and both routes have disadvantages. To minimize these shortcomings, a 24‐hr hybrid administration protocol (HPP) was developed. Our objective was to determine penicillin plasma concentrations in horses administered via HPP. Venous blood was collected from seven healthy horses administered IV potassium penicillin G at 0 and 6 hr and IM procaine penicillin G at 12 hr. Blood was collected at 2‐hr intervals from 0 to 20 hr and at 24 hr. Plasma penicillin concentrations were measured using liquid chromatography and mass spectrometry. Penicillin susceptibility from equine isolates was examined to determine pharmacodynamic targets. The MIC₉₀ of penicillin for 264 isolates of Streptococcus sp. was ≤0.06 μg/ml. For the 24‐hr dosing interval, the mean plasma penicillin concentration was >0.07 μg/ml. Five horses (72%) exceeded 0.06 μg/ml for 98% of the dosing interval, and two horses exceeded this value for 52%–65% of the dosing interval. The HPP achieved mean plasma penicillin concentrations in healthy adult horses above 0.07 μg/ml for a 24‐hr dosing interval. However, individual variations in plasma concentrations were apparent and deserve future clinical study.     

Pharmacokinetics,metabolism and excretion of celecoxib,a selective cyclooxygenase‐2 inhibitor,in horses

Celecoxib, a nonsteroidal anti‐inflammatory drug, is frequently used to treat arthritis in humans with minimal gastrointestinal side effect compared to traditional NSAIDs. The primary aim of this study was to determine the pharmacokinetic profile of celecoxib—a selective cyclooxygenase‐2 (COX‐2) inhibitor in horses. Six horses were administered a single oral dose of celecoxib at 2 mg/kg (body weight). After oral dosing, the drug reached a maximum concentration (mean ± SD) in blood of 1,088 ± 324 ng/ml in 4.58 hr. The elimination half‐life was 13.60 ± 3.18 hr, and the area under the curve was 24,142 ± 1,096 ng hr ml^?1. The metabolism of celecoxib in horses was via a single oxidative pathway in which the methyl group of celecoxib is oxidized to a hydroxymethyl metabolite and is further oxidized to form a carboxylic acid metabolite. Celecoxib is eliminated mainly through faeces as unchanged drug and as metabolites in urine. Therefore, instructions for a detection time following therapeutic dosing of celecoxib can be set by the racing practitioner and veterinarians to control illegal use in horse racing based on the results of this study.     

Comparative pharmacokinetics of minocycline in foals and adult horses

The objective of this study was to compare the pharmacokinetics of minocycline in foals vs. adult horses. Minocycline was administered to six healthy 6‐ to 9‐week‐old foals and six adult horses at a dose of 4 mg/kg intragastrically (IG) and 2 mg/kg intravenously (i.v.) in a cross‐over design. Five additional oral doses were administered at 12‐h intervals in foals. A microbiologic assay was used to measure minocycline concentration in plasma, urine, synovial fluid, and cerebrospinal fluid (CSF). Liquid chromatography–tandem mass spectrometry was used to measure minocycline concentrations in pulmonary epithelial lining fluid (PELF) and bronchoalveolar (BAL) cells. After i.v. administration to foals, minocycline had a mean (±SD) elimination half‐life of 8.5 ± 2.1 h, a systemic clearance of 113.3 ± 26.1 mL/h/kg, and an apparent volume of distribution of 1.24 ± 0.19 L/kg. Pharmacokinetic variables determined after i.v. administration to adult horses were not significantly different from those determined in foals. Bioavailability was significantly higher in foals (57.8 ± 19.3%) than in adult horses (32.0 ± 18.0%). Minocycline concentrations in PELF were higher than in other body fluids. Oral minocycline dosed at 4 mg/kg every 12 h might be adequate for the treatment of susceptible bacterial infections in foals.     

Effect of dosage and application mode of l‐carnitine on plasma lipid and egg‐yolk cholesterol of turkeys,hatchability of eggs and post‐hatch growth of their offsprings

The effect of dosage and application mode of l ‐carnitine on plasma lipid and egg‐yolk cholesterol of breeder turkeys, hatchability of eggs and post‐hatch growth response was investigated using 180 breeder hens. The hens were assigned to six dietary treatments in a 2 × 3 factorial arrangements of two application modes of l ‐carnitine (diet and drinking water) supplemented at 0, 50 and 100 ppm (mg/kg or mg/l) levels, respectively. Each treatment was replicated five times with six hens per replicate. Dietary inclusion of 50 ppm l ‐carnitine showed the lowest (p < 0.01) plasma total cholesterol (TC) and low‐density lipoprotein concentration (LDL). Breeder hens offered 50 ppm l ‐carnitine with no regard to application mode recorded the highest (p < 0.01) plasma high‐density lipoprotein (HDL). Hens offered 50 and 100 ppm l ‐carnitine irrespective of application mode also showed reduced (p < 0.01) egg‐yolk TC concentration at 32 weeks of age. Dietary supplementation of 50 ppm l ‐carnitine for breeder turkeys recorded the lowest (p < 0.01) egg‐yolk triglyceride (TG) at 40 weeks of age. Hens offered 50 ppm l ‐carnitine irrespective of application mode recorded the highest (p < 0.05) hen‐day egg production. Incidence of dead‐in‐shell also reduced (p < 0.05) with increasing dosage of l ‐carnitine. Dietary supplementation of 50 ppm and oral application in drinking water of 100 ppm l ‐carnitine for breeder turkeys resulted in highest (p < 0.05) egg fertility. Offsprings from breeder hens fed diets supplemented with l ‐carnitine recorded no post‐hatch mortality. Highest (p < 0.05) post‐hatch final live weight and weight gain was obtained with poults obtained from hens fed diet supplemented with 50 ppm l ‐carnitine. In conclusion, dietary supplementation of 50 ppm l ‐carnitine for turkey hens showed improved serum lipid profile, egg fertility, reduced dead‐in‐shell, egg‐yolk cholesterol and resulted in improved post‐hatch growth performance.     

Pharmacokinetics of tobramycin following intravenous,intramuscular, and intra‐articular administration in healthy horses

The objectives of this study were to examine the pharmacokinetics of tobramycin in the horse following intravenous (IV), intramuscular (IM), and intra‐articular (IA) administration. Six mares received 4 mg/kg tobramycin IV, IM, and IV with concurrent IA administration (IV+IA) in a randomized 3‐way crossover design. A washout period of at least 7 days was allotted between experiments. After IV administration, the volume of distribution, clearance, and half‐life were 0.18 ± 0.04 L/kg, 1.18 ± 0.32 mL·kg/min, and 4.61 ± 1.10 h, respectively. Concurrent IA administration could not be demonstrated to influence IV pharmacokinetics. The mean maximum plasma concentration (C_max) after IM administration was 18.24 ± 9.23 μg/mL at 1.0 h (range 1.0–2.0 h), with a mean bioavailability of 81.22 ± 44.05%. Intramuscular administration was well tolerated, despite the high volume of drug administered (50 mL per 500 kg horse). Trough concentrations at 24 h were below 2 μg/mL in all horses after all routes of administration. Specifically, trough concentrations at 24 h were 0.04 ± 0.01 μg/mL for the IV route, 0.04 ± 0.02 μg/mL for the IV/IA route, and 0.02 ± 0.02 for the IM route. An additional six mares received IA administration of 240 mg tobramycin. Synovial fluid concentrations were 3056.47 ± 1310.89 μg/mL at 30 min after administration, and they persisted for up to 48 h with concentrations of 14.80 ± 7.47 μg/mL. Tobramycin IA resulted in a mild chemical synovitis as evidenced by an increase in synovial fluid cell count and total protein, but appeared to be safe for administration. Monte Carlo simulations suggest that tobramycin would be effective against bacteria with a minimum inhibitory concentration (MIC) of 2 μg/mL for IV administration and 1 μg/mL for IM administration based on C_max:MIC of 10.     

Disposition of the anti‐ulcer medications ranitidine,cimetidine, and omeprazole following administration of multiple doses to exercised Thoroughbred horses

The use of anti‐ulcer medications, such as cimetidine, ranitidine, and omeprazole, is common in performance horses. The use of these drugs is regulated in performance horses, and as such a withdrawal time is necessary prior to competition to avoid a medication violation. To the authors' knowledge, there are no reports in the literature describing repeated oral administrations of these drugs in the horse to determine a regulatory threshold and related withdrawal time recommendations. Therefore, the objective of the current study was to describe the disposition and elimination pharmacokinetics of these anti‐ulcer medications following oral administration to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 20 mg/kg BID of cimetidine or 8 mg/kg BID of ranitidine, both for seven doses or 2.28 g of omeprazole SID for four doses. Blood samples were collected, serum drug concentrations were determined, and elimination pharmacokinetic parameters were calculated. The serum elimination half‐life was 7.05 ± 1.02, 7.43 ± 0.851 and 3.94 ± 1.04 h for cimetidine, ranitidine, and omeprazole, respectively. Serum cimetidine and ranitidine concentrations were above the LOQ and omeprazole and omeprazole sulfide below the LOQ in all horses studied upon termination of sample collection.     

A Bayesian approach for estimating detection times in horses: exploring the pharmacokinetics of a urinary acepromazine metabolite

We describe the population pharmacokinetics of an acepromazine (ACP) metabolite (2‐(1‐hydroxyethyl)promazine) (HEPS) in horses for the estimation of likely detection times in plasma and urine. ACP (30 mg) was administered to 12 horses, and blood and urine samples were taken at frequent intervals for chemical analysis. A Bayesian hierarchical model was fitted to describe concentration–time data and cumulative urine amounts for HEPS. The metabolite HEPS was modelled separately from the parent ACP as the half‐life of the parent was considerably less than that of the metabolite. The clearance (Cl/F_PM) and volume of distribution (V/F_PM), scaled by the fraction of parent converted to metabolite, were estimated as 769 L/h and 6874 L, respectively. For a typical horse in the study, after receiving 30 mg of ACP, the upper limit of the detection time was 35 h in plasma and 100 h in urine, assuming an arbitrary limit of detection of 1 lg/L and a small (≈0.01) probability of detection. The model derived allowed the probability of detection to be estimated at the population level. This analysis was conducted on data collected from only 12 horses, but we assume that this is representative of the wider population.     

The pharmacokinetics of dexmedetomidine administered as a constant rate infusion in horses

Dexmedetomidine, the most selective α₂‐adrenoceptor agonist in clinical use, is increasingly being used in both conscious and anaesthetized horses; however, the pharmacokinetics and sedative effects of this drug administered alone as an infusion are not previously described in horses. Seven horses received an infusion of 8 μg dexmedetomidine/kg/h for 150 min, venous blood samples were collected, and dexmedetomidine concentrations were assayed using liquid chromatography‐mass spectrometry (LC/MS) and analyzed using noncompartmental pharmacokinetic analysis. Sedation was scored as the distance from the lower lip of the horse to the ground measured in centimetre. The harmonic mean (SD) plasma elimination half‐life (Lambda z half‐life) for dexmedetomidine was 20.9 (5.1) min, clearance (Cl) was 0.3 (0.20) L/min/kg, and volume of distribution at steady‐state (Vd_ss) was 13.7 (7.9) L/kg. There was a considerable individual variation in the concentration of dexmedetomidine vs. time profile. The level of sedation covaried with the plasma concentration of dexmedetomidine. This implies that for clinical use of dexmedetomidine constant rate infusion in conscious horses, infusion rates can be easily adjusted to effect, and this is preferable to an infusion at a predetermined value.     

Biochemical markers of bone metabolism in draught andwarmblood horses

Concentrations of the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and osteocalcin (OC) have been determined in the serum of one hundred clinically healthy adult Draught or Warmblood horses. The correlation between these two markers has been evaluated and the influence of gender, age and type of horse described. No significant variations were observed between animals of different sex, but a significant inverse correlation (P<0.0001) with age was observed for both measured parameters. After correction for age, serum levels of OC were found to be lower in Draught [adjusted least square mean (LSM)=6.612μg. L⁻¹] than in Warmblood horses (adjusted LSM=8.596μg.L⁻¹), whereas levels of ICTP were higher in Draughts (adjusted LSM=8.035pg.L⁻¹) than in Warmbloods (adjusted LSM=6.643μg.L⁻¹). A significant correlation (P<0.0001) was observed between OC and ICTP. This correlation was stronger if the type of horse was taken into account in the statistical model. The ratio OC:ICTP was independent of gender and age. A higher OC:ICTP ratio in Warmbloods compared to the Draught horses might reflect a higher bone remodelling level of horses submitted to regular daily work. It was concluded that ICTP and OC are influenced by the type of horse, and probably reflect a physiological difference in bone remodelling between these animals.