Pharmacokinetics and Effects of Alkalization after Intravenous Administration of Eltenac in Horses

Eltenac (ELT) [4-(2,6-dichlorophenyl)amino-3-thiophene] is a non-steroidal anti-inflammatory drug (NSAID) that was developed for veterinary use in horses and cattle. The pharmacokinetics of ELT was evaluated in horses at 0.5 mg/kg body weight (BW) after single IV injection after 5 days of repeated IV administration and after a single IV injection in horses previously subjected to 250 mg/kg BW of sodium bicarbonate (NaHCO₃) as an alkalization treatment. The aim was to determine whether blood and subsequent urinary alkalization could modify the pharmacokinetics of ELT. Drug quantification was performed with serum and urine using high performance liquid chromatography with UV-visible detection. The results were also integrated with cyclo-oxygenase-inhibition literature data to review the dosage scheme of ELT in horses. After a single intravenous administration, ELT was characterized by rapid distribution (mean t½_λ1 = 0.18 ± 0.07 hour) and a short elimination half-life (mean t½_λ2 = 2.9 ± 0.68 hour). The volume of distribution was small (V_dss = 253.51 ± 47.55 mL/kg), which is likely because of the high percentage of drug protein binding (approximately 97%). The AUC_0-∞ and Cl_B were 6.92 ± 0.84 h*μg/mL and 73.2 ± 10 mL/h/kg, respectively. Repeated administration did not cause either accumulation or modification of the pharmacokinetic profile. The in vitro effective concentrations were maintained for a 6-hour period. The alkalization procedure appeared to accelerate drug elimination, as ELT was quantifiable only for 6 hours; however, the drug clearance was not significantly modified. Thus, the administration of alkaline compounds to accelerate the elimination of ELT is not completely confirmed.     

The pharmacokinetics of a slow-release theophylline preparation in horses after intravenous and oral administration

The pharmacokinetics of a slow-release theophylline formulation was investigated following intravenous and oral administration at 10 mg/kg in horses. A tricompartmental model was selected to describe the intravenous plasma profile. The elimination half-life (t1/2) was 16.91 ± 0.93 h, the apparent volume of distribution (V _d) was 1.35 ± 0.18 L/kg and the body clearance (Cl_B) was 0.061 ± 0.009 L kg^–1 h. After oral administration the half-life of absorption was 1.24 ± 0.30 h, and the calculated bioavailability was above 100%. Thet1/2 after oral administration was 18.51 ± 1.75 h, only a little longer than that after intravenous administration. The slow release formulation did not exhibit any advantage in prolonging thet1/2 of theophylline in the horse.     

Pharmacokinetics of thiamphenicol in Japanese quails (Coturnix japonica) after single intravenous and oral administrations

Thiamphenicol (TP) pharmacokinetics were studied in Japanese quails (Coturnix japonica) following a single intravenous (IV) and oral (PO) administration at 30 mg/kg BW. Concentrations of TP were determined with HPLC and were analyzed by a noncompartmental method. After IV injection, elimination half-life (t_1/2λz), total body clearance (Cl_tot) volume of distribution at steady state (V_dss), and mean residence time (MRT) of TP were 3.83 hr, 0.19 L/hr/kg, 0.84 L/kg, and 4.37 hr, respectively. After oral administration of TP, the peak plasma concentration (C_max) was 19.81 μg/ml and was obtained at 2.00 hr (t_max) postadministration. Elimination half-life (t_1/2λz) and mean absorption time (MAT) were 4.01 hr and 1.56 hr, respectively. The systemic bioavailability following oral administration of TP was 78.10%. TP therapy with an oral dosage of 30 mg/kg BW is suggested for a beneficial clinical effect in quails.     

Determination of Pasture Dry Matter Intake Rates in Different Seasons and Their Application in Grazing Management

Eight mature horses weighing 576 ± 32 kg (mean ± SD) were used to compare differences in pasture dry matter (DM) intake rate in October (period 1), February (period 2), and May (period 3). Horses were randomly assigned to a pair of adjacent 5 m × 5 m grazing cells containing nontoxic, endophyte-infected tall fescue. Horses had access to each cell for 4 hours. Pasture DM intake rate was estimated over the entire 8-hour period by measuring the pre- and postgrazing herbage mass within each cell and was expressed as kg DM/100 kg body weight (BW)/hr. Mean 8-hour DM intake rate in period 1 (0.17 ± 0.01 kg DM/100 kg BW/hr) was greater (P < .001) than for period 2 (0.09 ± 0.01 kg DM/100 kg BW/hr) and period 3 (0.11 ± 0.01 kg DM/100 kg BW/hr), but it was not different (P = .274) between periods 2 and 3. A second experiment using the same eight horses was conducted immediately after the first experiment, within each season, to determine whether the DM intake rates derived from the first experiment could be used along with estimates of maintenance digestible energy (DE) requirements and pasture DE concentrations to predict the amount of grazing time required for a horse to consume only its maintenance DE requirement and maintain zero BW change over a 6-week period. Grazing time necessary to maintain zero BW change was accurately predicted for period 1 only.     

Subspecies Studies: Pharmacokinetics and Pharmacodynamics of a Single Intravenous Dose of Xylazine in Adult Mules and Adult Haflinger Horses

This study reveals the different effectiveness of xylazine in mules compared with horses. Fourteen adult mules (mean body weight ± standard deviation, 466 ± 89 kg) and six adult Haflinger horses (483 ± 39 kg) chosen from a single livestock operation in Germany received 0.6 mg of the α₂-agonist xylazine administered intravenously per kilogram of body weight. Principal pharmacokinetic and pharmacodynamic parameters were determined while the animals received a routine dental treatment. To objectively assess the depth of sedation, a variety of behavioral and clinical parameters were assessed and transferred to a scaled score system. Compared with the Haflinger horses, the depth of sedation in mules differed significantly between 10 and 45 minutes after xylazine administration. In the mule, sedation was good during the first 10 minutes, moderate at 15 minutes, and insufficient at 30 minutes. In the horse, sedation was excellent during the first 15 minutes, moderate at 30 minutes, and insufficient at 45 minutes. Moreover, significant (P < .05) subspecies differences in the pharmacokinetics of xylazine were detected between the mules and the horses. Data analysis followed the two-compartment model, which had a correlation with the measured data of R² = .99. Values for t_1/2β (half-life during elimination), mean residence time, mean residence time_(0-tz) (residence time on last measuring time point above limit of quantification), k₂₁ (velocity constant for distribution from peripheral to central compartment), β (velocity constant during elimination), and B (relative y-intercept) varied significantly between the two subspecies.     

Pharmacokinetics of ascorbic acid in horses

The pharmacokinetics of ascorbic acid were studied in 29 horses after intravenous (iv), subcutaneous, intramuscular (im) and oral administration. Following iv injection of 5 and 10 g ascorbic acid, respectively, a biphasic decline of ascorbic acid serum levels was found, indicating that the vitamin distributes in the body according to a two-compartment open model. The apparent volume of distribution (average value for V_d(ss)= 0.6 litre/kg) was approximately equivalent to the volume of total body water. The terminal half-life of the biexponential serum level-time curve (t_1/2β) varied between 5 and 17 h. Both distribution and elimination were found to be positively correlated with the iv dose administered. Following subcutaneous and im injection, the average bioavailability of ascorbic acid amounted to 82 and 61 per cent, respectively. However, both routes of administration gave rise to marked local irritation. Following oral administration, the systemic availability of ascorbic acid was very poor. Serum levels in most experiments were not increased above the endogenous pre-administration values of the vitamin. Thus, in horses iv injection appears to be the only satisfactory route of administration of ascorbic acid if supplementation is required.     

Pharmacokinetics and bioavailability of a long-acting formulation of cephalexin after intramuscular administration to cats

The pharmacokinetic profile and bioavailability of a long-acting formulation of cephalexin after intramuscular administration to cats was investigated. Single intravenous (cephalexin lysine salt) and intramuscular (20% cephalexin monohydrate suspension) were administered to five cats at a dose rate of 10 mg/kg. Serum disposition curves were analyzed by noncompartmental approaches. After intravenous administration, volume of distribution (V_z), total body clearance (Cl_t), elimination constant (λ_z), elimination half-life (t_½λ) and mean residence time (MRT) were: 0.33 ± 0.03 L/kg; 0.14 ± 0.02 L/h kg, 0.42 ± 0.05 h⁻¹, 1.68 ± 0.20 h and 2.11 ± 0.25 h, respectively. Peak serum concentration (C_max), time to peak serum concentration (T_max) and bioavailability after intramuscular administration were 15.67 ± 1.95 μg/mL, 2.00 ± 0.61 h and 83.33 ± 8.74%, respectively.     

Pharmacokinetics of Pefloxacin in Goats after Intravenous or Oral Administration

The plasma concentrations and pharmacokinetics of the fluoroquinolone antimicrobial agent pefloxacin, following the administration of a single intravenous (10 mg/kg) or oral (20 mg/kg) dose, were investigated in healthy female goats. The antimicrobial activity in plasma was measured at predetermined times after drug administration by an agar well diffusion microbiological assay, using Escherichia coli (ATCC 25922) as the test organism. Concentrations of the drug 0.25 g/ml were maintained in plasma for up to 6 and 10 h after intravenous (IV) or oral administration of pefloxacin, respectively. The concentration–time data for pefloxacin in plasma after IV or oral administration conformed to two- and one-compartment open models, respectively. Plasma pefloxacin concentrations decreased rapidly during the initial phase after IV injection, with a distribution half-life (t _1/2 ) of 0.10±0.01 h. The terminal phase had a half-life (t _1/2 ) of 1.12±0.21 h. The volume of distribution at steady state (V _dss), mean residence time (MRT) and total systemic clearance (Cl_B) of pefloxacin were 1.08±0.09 L/kg, 1.39±0.23 h and 821±88 (ml/h)/kg, respectively. Following oral administration of pefloxacin, the maximum concentration in the plasma (C _max) was 2.22±0.48 g/ml and the interval from administration until maximum concentration (t _max) was 2.3±0.7 h. The absorption half-life (t _{1/2 ka}), mean absorption time (MAT) and elimination half-life of pefloxacin were 0.82±0.40, 4.2±1.0 and 2.91±0.50 h, respectively. The oral bioavailability of pefloxacin was 42%±5.8%. On the basis of the pharmacokinetic data, a dosage regimen of 20 mg/kg, IV at 8 h intervals or orally twice daily, is suggested for treating infections caused by drug-sensitive pathogens in goats.     

The pharmacokinetics of thiamphenicol in lactating cows

The pharmacokinetics of thiamphenicol were studied after intravenous and intramuscular administration of 25 mg/kg body weight in lactating cows. Distribution (t _1/2) and elimination (t _1/2) half-lives of 6.10±1.39 min and 1.60±0.30 h, respectively, were obtained after intravenous administration. The body clearance was 3.9±0.077 ml/kg per min and the apparent volume of distribution was 1220.79±256.67 ml/kg. The rate at which thiamphenicol appeared in the milk, as indicated by the penetration half-life (t _1/2P) (serum to quarters), was found to be 36.89±11.14 min. The equivalent elimination half-life (t _1/2E) (quarters to serum) from the milk was 3.62±1.06 h and the peak thiamphenicol concentration in the milk was 23.09±3.42 µg/ml at 2.5±0.32 h.After intramuscular injection, the elimination half-life was 2.2±0.40 h, the absorption half-life was 4.02±1.72 min and the peak concentration in the serum was 30.90±5.24 µg/ml at 23±8.4 min. The bioavailability after intramuscular administration approached 100%. The penetration half-life was 50.59±6.87 min, the elimination half-life was 5.91±4.97 h and the mean peak concentration in the milk was 17.37±2.20 µg/ml at 3.4±0.22 h.Abbreviations AUC area under the concentration-time curve - CAP chloramphenicol - C _max peak concentration - IM intramuscular - IV intravenous - TAP thiamphenicol - t _1/2 distribution half-life - t _1/2 elimination half-life - V _c volume of central compartment - V _d volume of distribution     

Pharmacokinetics of Tramadol and Its Metabolites M1, M2, and M5 in Donkeys after Intravenous and Oral Immediate Release Single-Dose Administration

Tramadol (T) is a centrally acting analgesic structurally related to codeine and morphine. Recently, T has been reported to be metabolized faster to inactive metabolites in goats, dogs, and horses than in cats. Clinical effectiveness of T has been questioned in species that mainly metabolize this molecule to inactive metabolites, suggesting that this drug could be not suitable as effective and safe treatment for pain as in humans. The purpose of the study is to determine the pharmacokinetics of T and its main metabolites in donkeys to evaluate its prospective use in clinical practice. The subjects were 12 male donkeys, 6 to 9 years old and weighing 300 to 380 kg. Each subject received a single dose of 2.5 mg/kg T either orally or intravenously. Plasma T, O-desmethyltramadol (M1), N-desmethyltramadol (M2), and N-,O-didesmethyltramadol (M5) concentrations were evaluated by high-pressure liquid chromatography (HPLC). Pharmacokinetic parameters in both administrations were calculated according to a non-compartmental model. After intravenous administration, T was detectable up to 10 hours, whereas M1, M2, and M5 were detectable from 15 minutes up to 6 hours. The total amount of M2 was greater than M1, which was greater than M5. The T area under the concentration/time curve (AUC), T_1/2 λz (terminal half-life), and Cl/F (Clearance/F where F is the fraction of the drug absorbed) were 14,522 ± 2,554 h/ng/mL, 1.55 ± 0.74 hours, and 167 ± 22.3 mL/h/kg, respectively. After oral administration, T was detectable up to 8 hours to a lower extent than after the intravenous route. The total amount of M2 was greater than M5, which was greater than M1. The T AUC, T_1/2 λz, and Cl/F were 4,624 ± 2,002 h/ng/mL, 4.22 ± 2.32 hours, and 495 ± 170 mL/h/kg, respectively. The bioavailability of the oral formulation was 11.7 ± 5.1%. In conclusion, despite the effectiveness of intravenous administration of T, oral administration did not reach the minimum plasma concentration of both M1 and parental drug reported in humans as needed to achieve analgesia in donkeys.     

Pharmacokinetic profiles of florfenicol in spotted halibut,Verasper variegatus,at two water temperatures

The pharmacokinetic profiles of florfenicol in the spotted halibut (Verasper variegatus) were investigated at 15 and 20°C water temperatures, respectively. Florfenicol content in plasma samples was analyzed using an HPLC method. Drug concentration versus time data were best fitted to a three‐compartment model after a single intravenous administration (15 mg/kg BW), and fitted to a two‐compartment model after an oral administration (30 mg/kg BW) at 15 and 20°C. The florfenicol concentration in the blood increased slowly during the 12 hr following an oral administration at 15°C, with a peak concentration (C_max) of 9.1 mg/L, and then declined gradually. The half‐lives of absorption, distribution, and elimination phase were 2.18, 5.66 and 14.25 hr, respectively. The bioavailability (F) was calculated to be 24.14%. After an oral administration at 20°C, shorter half‐lives of absorption (1.33 hr), distribution (2.51 hr) and elimination (9.71 hr), a higher C_max (12.2 mg/L), and a similar F (23.98%) were found. Based on the pharmacokinetics and pharmacodynamics, an oral dose of 30 mg/kg BW was suggested to be efficacious for bacterial disease control in spotted halibut farming.     

Pharmacokinetics and bioavailability of flumequine in blunt snout bream (Megalobrama amblycephala) after intravascular and oral administrations

In this study, the pharmacokinetic profile of flumequine (FMQ) was investigated in blunt snout bream (Megalobrama amblycephala) after intravascular (3 mg/kg body weight (b.w.)) and oral (50 mg/kg b.w.) administrations. The plasma samples were determinedby ultra‐performance liquid chromatography (UPLC) with fluorescence detection. After intravascular administration, plasma concentration–time curves were best described by a two‐compartment open model. The distribution half‐life (t_1/2α), elimination half‐life (t_1/2β), and area under the concentration–time curve (AUC) of blunt snout bream were 0.6 h, 25.0 h, and 10612.7 h·μg/L, respectively. After oral administration, a two‐compartment open model with first‐order absorption was also best fit the data of plasma. The t_1/2α, t_1/2β, peak concentration (C_max), time‐to‐peak concentration (T_max), and AUC of blunt snout bream were estimated to be 2.5 h, 19.7 h, 3946.5 μg/L, 1.4 h, and 56618.1 h. μg/L, respectively. The oral bioavailability (F) was 32.0%. The pharmacokinetics of FMQ in blunt snout bream displayed low bioavailability, rapid absorption, and rapid elimination.     

Determination of oral tramadol pharmacokinetics in horses

The determination of the pharmacokinetic parameters of tramadol in plasma and a better characterization of its metabolites after oral administration to horses is necessary to design dosage regimens to achieve target plasma concentrations that are associated with analgesia. The purpose of this study was to determine the pharmacokinetics and elimination pattern in urine of tramadol and its metabolites after oral administration to horses. Tramadol was administered orally to six horses and its half-life, T_max and C_max in plasma were 10.1, 0.59 h, and 132.7 ng/mL, respectively. The half-life, T_max and C_max for M1 in plasma were 4.0, 0.59 h, and 28.0 ng/mL, respectively. Tramadol and its metabolites were detectable in urine between 1 and 24 h after the administration. In conclusion, the PK data reported in this study provides information for the design of future studies of tramadol in horses.     

The fate and tissue disposition of deoxynivalenol in broiler chickens

To evaluate the fate of deoxynivalenol (DON) in broilers, DON was administered either intravenously or orally to broilers at a dose of 1 mg/kg BW. Concentrations of DON in plasma were measurable up to 4 hr and 2 hr after intravenous and oral administration, respectively. Following intravenous administration, the values for the elimination half-life, the volume of distribution and the clearance were 1.25 ± 0.25 hr, 7.55 ± 2.03 l/kg and 4.16 ± 0.42 l/hr/kg, respectively. The oral bioavailability was 15.46 ± 4.02%. DON was detectable in all tissues examined after oral administration. These results suggest that DON is able to penetrate into the various tissues in broilers, though poorly absorbed from their gastrointestinal tract.     

Blood buffering in sedentary miniature horses after administration of sodium bicarbonate in single doses of varying amounts

Blood acid-base and electrolyte status was studied in four sedentary Miniature Horses treated with 200, 300, 400 and 500 mg of sodium bicarbonate (NaHCO₃) per kg of body weight (BW). Arterial blood was collected before treatment with NaHC0₃ and each hour for 5 h after treatment. All treatments resulted in an increase in blood pH, bicarbonate (HCO₃⁻) concentration and base excess (BE) by 1 h post-dosage, which continued through the 5th hour (P < .05). Treatment with 200 mg NaHC0₃/kg BW resulted in less elevated blood HCO₃⁻ concentrations (P < .03) and BE values (P < .01) when compared to the other treatments. Following dosing with NaHCO₃, plasma Na⁺ concentrations increased among all treatments but declined to initial values by 3 h post-treatment. The 200 mg NaHCO₃/kg BW dosage resulted in the smallest increases in plasma Na⁺ concentrations (P < .03). Both plasma K⁺ and Ca⁺⁺ concentrations were lower (P < .05) among all treatment groups 1 h post-dosage but returned to initial values by 5 h and 3 h posttreatment, respectively, with no differences (P >.05) among treatments. All NaHCO₃ dosages increased blood buffering capacity as indicated by increased blood pH, HCO₃⁻ concentration and BE. Maximum blood pH, HCO⁻₃ concentration and BE was reached using a dosage of 300 mg NaHCO₃/kg BW. Also, all treatments altered the plasma electrolyte concentrations.     

Evaluation of the Effects of Live Yeast Supplementation on Apparent Digestibility of High-Fiber Diet in Mature Horses Using the Acid Insoluble Ash Marker Modified Method

The objective of this study was to evaluate the effects of live yeast (LY) in a high-fiber diet on nutrients digestibility in mature horses. Six Italian Standardbred mares (weight: 544 ± 14 kg; age: 15.30 ± 3.9 years) in a two-period crossover design were fed a basal diet (2.5% body weight [BW]) in a 70:30 forage:concentrate ratio with (LY) or without (CTR) the administration of 4.6 × 10¹⁰ colony forming unit (CFU)/d of Saccharomyces cerevisiae (MUCL 39885). An adaptation to the diet of 14 days, and an 18-day administration phase, with fecal collection in the last 3 days were performed for each period. Yeast was top-dressed twice a day during the concentrate meal (12:30 am and 09:00 pm). Change in BW was measured at the beginning of each experimental phase and the diet adjusted accordingly, and individual feed intake was recorded daily. Concentrate samples were collected at the beginning of each confinement period and individual hay samples were obtained for each confinement day 38 hours before fecal collection. No influence of LY was observed on BW change (P = .64), feed intake (P = .48), hay intake (P = .48), or concentrate intake (P = .47). S cerevisiae supplementation improved apparent digestibility of dry matter (64.5% vs. 60.1%, P = .03), organic matter (66.1% vs. 61.6%, P = .04), neutral detergent fiber (42.5% vs. 35.9%, P = .04), and acid detergent fiber (36.5% vs. 28.0%, P = .03) with a positive trend on crude protein (P = .08). In the present study, the administration of LY to horses significantly improved the digestion of the fiber fractions of the diet.     

Metabolism,pharmacokinetics and selected pharmacodynamic effects of codeine following a single oral administration to horses

ObjectiveTo describe the pharmacokinetics and selected pharmacodynamic variables of codeine and its metabolites in Thoroughbred horses following a single oral administration.Study designProspective experimental study.AnimalsA total of 12 Thoroughbred horses, nine geldings and three mares, aged 4–8 years.MethodsHorses were administered codeine (0.6 mg kg^–1) orally and blood was collected before administration and at various times until 120 hours post administration. Plasma and urine samples were collected and analyzed for codeine and its metabolites by liquid chromatography–mass spectrometry, and plasma pharmacokinetics were determined. Heart rate and rhythm, step counts, packed cell volume and total plasma protein were measured before and 4 hours after administration.ResultsCodeine was rapidly converted to the metabolites norcodeine, codeine-6-glucuronide (C6G), morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Plasma codeine concentrations were best represented using a two-compartment model. The C_max, t_max and elimination t_½ were 270.7 ± 136.0 ng mL^–1, 0.438 ± 0.156 hours and 2.00 ± 0.534 hours, respectively. M3G was the main metabolite detected (C_max 492.7 ± 35.5 ng mL^–1), followed by C6G (C_max 96.1 ± 33.8 ng mL^–1) and M6G (C_max 22.3 ± 4.96 ng mL^–1). Morphine and norcodeine were the least abundant metabolites with C_max of 3.17 ± 0.95 and 1.42 ± 0.79 ng mL^–1, respectively. No significant adverse or excitatory effects were observed.Conclusions and clinical relevanceFollowing oral administration, codeine is rapidly metabolized to morphine, M3G, M6G, C6G and norcodeine in horses. Plasma concentrations of M6G, a presumed active metabolite of morphine, were comparable to concentrations reported previously following administration of an analgesic dose of morphine to horses. Codeine was well tolerated based on pharmacodynamic variables and behavioral observations.     

Pharmacokinetics of benzydamine in dairy cows following intravenous or intramuscular administration

Five lactating cows were given benzydamine hydrochloride by rapid intravenous (0.45 mg/kg) and by intramuscular (0.45 and 1.2 mg/kg) injection in a crossover design. The bioavailability, pharmacokinetic parameters and excretion in milk of benzydamine were evaluated. After intravenous administration, the disposition kinetics of benzydamine was best described using a two-compartment open model. Drug disposition and elimination were fast (t _1/2: 11.13±3.76 min;t _1/2: 71.98±24.75 min; MRT 70.69±11.97 min). Benzydamine was widely distributed in the body fluids and tissues (V _d(area): 3.549±1.301 L/kg) and characterized by a high value for body clearance (33.00±5.54 ml/kg per min). After intramuscular administration the serum concentration-time curves fitted a one-compartment open model. Following a dose of 0.45 mg/kg, theC _max value was 38.13±4.2 ng/ml at at _max of 67.13±4.00 min; MAT and MRT were 207.33±22.64 min and 278.01±12.22 min, respectively. Benzydamine bioavailability was very high (92.07%±7.08%). An increased intramuscular dose (1.2 mg/kg) resulted in longer serum persistence (MRT 420.34±86.39 min) of the drug, which was also detectable in milk samples collected from both the first and second milking after treatment.Abbreviations HPLC high-pressure liquid chromatography - IC50 concentration to inhibit the activity of an organism by 50% - IM intramuscular(ly) - IV intravenous(ly) - NSAID non-steroidal antiinflammatory drugs - pK _a negative logarithm of the ionization constant (K _a) of a drug; other abbreviations are listed in footnotes to tables     

Pharmacokinetics and Safety of Oral Administration of Meloxicam to Foals

Background

The pharmacokinetics, efficacy, and safety of meloxicam have been evaluated in adult horses, but not foals. Physiologic differences between neonates and adults might alter drug pharmacokinetics and therapeutic index.

Hypotheses

The pharmacokinetics of meloxicam will be different in foals compared with adult horses, and foals could be at increased risk for adverse drug effects.

Animals

Twenty lightbreed foals less than 6 weeks of age at commencement of the study.

Methods

Single and repeated oral dose pharmacokinetics were determined for meloxicam (0.6 mg/kg) in 10 foals. The safety of the drug was further evaluated in a 2nd group of 10 foals in a randomized blinded prospective study.

Results

Plasma concentrations after a single oral dose of meloxicam (0.6 mg/kg) and time to maximum plasma concentration were similar to adult horses. However, drug clearance was much more rapid in foals (elimination half‐life 2.48 ± 0.25 hours). Administration of 0.6 mg/kg every 12 hours was well tolerated by foals for up to 3 weeks, with no evidence of drug accumulation in plasma. Adverse effects observed in adult horses at higher dose rates were not observed in foals given 1.8 mg/kg twice daily for 7 days.

Conclusions and clinical importance

Meloxicam at an oral dose rate of 0.6 mg/kg every 12 hours provided plasma concentrations likely to be therapeutic. In contrast to findings for other NSAIDs, foals appeared more resilient to the adverse effects of this drug than was observed in adult horses.     

Pharmacokinetics of florfenicol after intravenous and intramuscular administration in New Zealand White rabbits

The pharmacokinetic disposition and bioavailability of florfenicol (FF) were determined after single intravenous (i.v.) and intramuscular (i.m.) administrations of 25 mg/kg b.w. to ten healthy New Zealand White rabbits. Plasma FF concentrations were determined by high-performance liquid chromatography (HPLC). The plasma pharmacokinetic values for FF were best described by a one-compartment open model. The elimination half-life (t_1/2β) was different (p < 0.05) however, the area under curve (AUC) was similar (p > 0.05) after i.v. and i.m. administrations. FF was rapidly eliminated (t_1/2β 1.49 ± 0.23 h), slowly absorbed and high (F, 88.75 ± 0.22%) after i.m. injection. In addition, FF was widely distributed to the body tissues (V_ss 0.98 ± 0.05 L/kg) after i.v. injection. In this study the time that plasma concentration exceeded the concentration of 2 μg/mL was approximately 6 h. For bacteria with MIC of 2 μg/mL, frequent administration at this dose would be needed to maintain the concentration above the MIC. However, it is possible that rabbit pathogens may have MIC values less than 2 μg/mL which would allow for less frequent administration. Further studies are necessary to identify the range of MIC values for rabbit pathogens and to identify the most appropriate PK-PD parameter needed to predict an effective dose.