Comparative disposition of tripelennamine in horses and camels after intravenous administration

The pharmacokinetics of tripelennamine (T) was compared in horses (n = 6) and camels (n = 5) following intravenous (i.v.) administration of a dose of 0.5 mg/kg body weight. Furthermore, the metabolism and urinary detection time was studied in camels. The data obtained (median and range in brackets) in camels and horses, respectively, were as follows: the terminal elimination half-lives were 2.39 (1.91-6.54) and 2.08 (1.31-5.65) h, total body clearances were 0.97 (0.82-1.42) and 0.84 (0.64-1.17)L/h/kg. The volumes of distribution at steady state were 2.87 (1.59-6.67) and 1.69 (1.18-3.50) L/kg, the volumes of the central compartment of the two compartment pharmacokinetic model were 1.75 (0.68-2.27) and 1.06 (0.91-2.20) L/kg. There was no significant difference (Mann-Whitney) in any parameter between camels and horses. The extent of protein binding (mean +/- SEM) 73.6 + 8.5 and 83.4 +/- 3.6% for horses and camels, respectively, was not significantly statistically different (t-test). Three metabolites of T were identified in urine samples of camels. The first one resulted from N-depyridination of T, with a molecular ion of m/z 178, and was exclusively eliminated in conjugate form. This metabolite was not detected after 6 h of T administration. The second metabolite, resulted from pyridine ring hydroxylation, had a molecular ion of m/z 271, and was also exclusively eliminated in conjugate form. This metabolite could be detected in urine sample for up to 12 h after T administration. The third metabolite has a suspected molecular ion of m/z 285, was eliminated exclusively in conjugate form and could be detected for up to 24 h following T administration. T itself could be detected for up to 27 h after i.v. administration, with about 90% of eliminated T being in the conjugated form.     

Caffeine clearance in the horse

The pharmacokinetic properties of intravenously administered caffeine were studied in 10 horses using a commercially available automated enzyme immunoassay. The harmonic mean for the distribution half-life was 5.2 min (range 1.4–18.7). The harmonic mean for the elimination half-life was 10.18 h (range 6.82–20.92). The harmonic mean of the volume of distribution was 0.32 L/kg (range 0.22–0.53). There was no correlation between the dose of caffeine/kg body weight and the elimination half-life (Spearman's coefficient of rank correlation =0.19).Abbreviations AUC area under the serum concentration-time curve - AUMC area under the moment curve - BSP sulphobromophthalein - ICG indocyanine green - SD standard deviation - t _1/2 elimination half-life - V _c apparent volume of the central compartment - V _d(ss) apparent volume of distribution at steady state     

The disposition of diclofenac in camels after intravenous administration

The pharmacokinetics of diclofenac was studied in camels (Camelus dromedarus) (n=6) following intravenous (i.v.) administration of a dose of 2.5 mg kg(-1) body weight. The metabolism and urinary detection time were also studied. The results obtained (median and range) were as follows: the terminal elimination half-life (t(1/2beta)) was 2.35 (1.90-2.73)h, total body clearance (Cl(T)) was 0.17 (0.16-0.21)lh kg(-1). The volume of distribution at steady state (V(SS)) was 0.31 (0.21-0.39)l(-1)kg(-1), the volume of the central compartment of the two compartment pharmacokinetic model (V(C)) was 0.15 (0.11-0.17)l kg(-1). Five metabolites of diclofenac were tentatively identified in urine and were excreted mainly in conjugate form. The main metabolite was identified as hydroxy diclofenac. Both diclofenac and hydroxy diclofenac, appear to be the main elimination route for diclofenac when administered i.v. in camels. Diclofenac could be identified up to 4 days following i.v. administration in camels using a sensitive gas chromatography/mass spectrometry (GC/MS) method.     

Effect of body weight on the pharmacokinetics of flunixin meglumine in miniature horses and quarter horses

In most species, large variations in body size necessitate dose adjustments based on an allometric function of body weight. Despite the substantial disparity in body size between miniature horses and light‐breed horses, there are no studies investigating appropriate dosing of any veterinary drug in miniature horses. The purpose of this study was to determine whether miniature horses should receive a different dosage of flunixin meglumine than that used typically in light‐breed horses. A standard dose of flunixin meglumine was administered intravenously to eight horses of each breed, and three‐compartmental analysis was used to compare pharmacokinetic parameters between breed groups. The total body clearance of flunixin was 0.97 ± 0.30 mL/min/kg in miniature horses and 1.04 ± 0.27 mL/min/kg in quarter horses. There were no significant differences between miniature horses and quarter horses in total body clearance, the terminal elimination rate, area under the plasma concentration versus time curve, apparent volume of distribution at steady‐state or the volume of the central compartment for flunixin (P > 0.05). Therefore, flunixin meglumine may be administered to miniature horses at the same dosage as is used in light‐breed horses.     

Lack of gender effect on the pharmacokinetics and pharmacodynamics of dexamethasone in the camel after intravenous administration

The pharmacokinetics and pharmacodynamics of dexamethasone were studied in six male and six female camels after a single intravenous dose (0.05 mgkg(-1) body weight) of dexamethasone. The pharmacokinetic parameters of the two-compartment pharmacokinetic model for female and male camels, respectively (mean+/-SEM) were as follows: terminal elimination half-lives were 8.02+/-1.15 and 7.33+/-0.80 h, total body clearances were 95.5+/-16.0 and 124.5+/-11.9 ml h(-1) per kg, volumes of distribution at steady state were 0.72+/-0.08 and 0.87+/-0.14 litre kg(-1), and the volumes of the central compartment were 0.12+/-0.02 and 0.17+/-0.02 litre kg(-1). There was no significant difference in any pharmacokinetic parameter between female and male camels. Pharmacodynamic effects were evaluated by measuring endogenous plasma cortisol, circulating lymphocytes and neutrophils numbers and were analysed using indirect pharmacokinetic/pharmacodynamic models. The estimated IC50 of dexamethasone for cortisol and lymphocytes for female and male camels were 3.74+/-0.99 and 2.28+/-1.09 and 2.63+/-0.71 and 2.41+/-0.79 ng ml(-1), respectively. The EC50 for neutrophils for female and male camels were 24.5+/-5.83 and 20.2+/-3.82 ng ml(-1), respectively. There was no significant difference in any pharmacodynamic parameter between female and male camels. Dexamethasone in urine could be detected for 4-5 days by enzyme-linked immunosorbent assay and for 3-4 days by liquid chromatography/mass spectrometry after an intravenous dose of 0.05 mg kg(-1) body weight.     

The pharmacokinetics of glycopyrrolate in Standardbred horses

The disposition of plasma glycopyrrolate (GLY) is characterized by a three‐compartment pharmacokinetic model after a 1‐mg bolus intravenous dose to Standardbred horses. The median (range) plasma clearance (Clp), volume of distribution of the central compartment (V₁), volume of distribution at steady‐state (Vss), and area under the plasma concentration–time curve (AUC_0‐inf) were 16.7 (13.6–21.7) mL/min/kg, 0.167 (0.103–0.215) L/kg, 3.69 (0.640–38.73) L/kg, and 2.58 (2.28–2.88) ng*h/mL, respectively. Renal clearance of GLY was characterized by a median (range) of 2.65 (1.92–3.59) mL/min/kg and represented approximately 11.3–24.7% of the total plasma clearance. As a result of these studies, we conclude that the majority of GLY is cleared through hepatic mechanisms because of the limited extent of renal clearance of GLY and absence of plasma esterase activity on GLY metabolism. Although the disposition of GLY after intravenous administration to Standardbred horses was similar to that in Thoroughbred horses, differences in some pharmacokinetic parameter estimates were evident. Such differences could be attributed to breed differences or study conditions. The research could provide valuable data to support regulatory guidelines for GLY in Standardbred horses.     

Pharmacokinetic, metabolism and withdrawal time of orphenadrine in camels (Camelus dromedarius) after intravenous administration

The pharmacokinetics of orphenadrine (ORPH) following a single intravenous (i.v.) dose was investigated in six camels (Camelus dormedarius). Orphenadrine was extracted from the plasma using a simple sensitive liquid–liquid extraction method and determined by gas chromatography/mass spectrometry (GC/MS). Following i.v. administration plasma concentrations of ORPH decline bi-exponentially with distribution half-life (t_1/2α) of 0.50 ± 0.07 h, elimination half-life (t_1/2β) of 3.57 ± 0.55 h, area under the time concentration curve (AUC) of 1.03 ± 0.10 g/h l⁻¹. The volume of distribution at steady state (Vd_ss) 1.92 ± 0.22 l kg⁻¹, volume of the central compartment of the two compartment pharmacokinetic model (V_c) 0.87 ± 0.09 l kg⁻¹, and total body clearance (Cl_T) of 0.60 ± 0.09 l/h kg⁻¹. Three orphenadrine metabolites were identified in urine samples of camels. The first metabolite N-desmethyl-orphenadrine resulted from N-dealkylation of ORPH with molecular ion m/z 255. The second N,N-didesmethyl-orphenadrine, resulted from N-didesmethylation with molecular ion m/z 241. The third metabolite, hydroxyl-orphenadrine, resulted from the hydroxylation of ORPH with molecular ion m/z 285. ORPH and its metabolites in camel were extensively eliminated in conjugated form. ORPH remains detectable in camel urine for three days after i.v. administration of a single dose of 350 mg orphenadrine aspartate.     

Analysis of equine cisterna magna cerebrospinal fluid for the presence of some monoamine neutrotransmitters and transmitter metabolites

Small volumes (0.05 ml) of cisterna magna cerebrospinal fluid (CSF) from 23 neurologically normal horses were analysed for the monoamine neurotransmitters dopamine, norepinephrine, epinephrine, serotonin and their metabolites using high pressure liquid chromatography and electrochemical detection. Two metabolites, homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were present in all CSF samples. The deaminated and methylated metabolite of dopamine, HVA, was present at a mean concentration of 42.33±3.14 ng/ml of CSF. The deaminated metabolite of serotonin, 5-HIAA, was present at a mean concentration of 45.52±3.65 ng/ml of CSF. A positive correlation was found between the CSF concentrations of HVA and 5-HIAA (r=0.72, p=0.0003). The mean ratio of HVA to 5-HIAA concentrations was 1.07±0.05. The ratios of HVA to 5-HIAA concentrations were found to be more indicative of the serotonergic metabolite 5-HIAA (r=–0.62, p=0.0016) than the dopaminergic metabolite HVA (r=0.11, p=0.60). There was a stronger relationship between the concentrations of 5-HIAA and the ratios of HVA to 5-HIAA in male CSF (r=–0.85, p=0.0006) than in female CSF (r=–0.54, p=0.01).Concentrations of CSF neurotransmitter metabolites were evaluated in horses grouped by age (0–4, 5–9 and 10–13 years). The youngest group of horses had a significantly (p=0.003) greater CSF concentration of HVA than of 5-HIAA. The 10–13-year-old horses had a significantly (p=0.02) lower mean CSF HVA concentration than the 0–4-year-old horses. No age-related differences in CSF 5-HIAA concentrations were detected.     

Effect of feeding increasing quantities of starch on glycaemic and insulinaemic responses in healthy horses

The aim of this study was to investigate the effect of increasing the intake of starch on the glycaemic and insulinaemic responses of horses. A cross-over study design was used in which four horses were fed increasing amounts of a compound feed (0.5–3.5 kg) to provide 0.3, 0.6, 0.8, 1.1, 1.4 and 2 g starch/kg bodyweight (BW)/meal. The glycaemic response increased with starch intake (P < 0.05), while feeding <1.1 g starch/kg BW resulted in a lowered response, compared to when 1.1–2 g starch/kg BW was fed (P < 0.01). The results suggested that insulin responses may be more appropriate to define the effect of feeding different starch levels than glycaemic responses. A starch intake of <1.1 g/kg BW/meal produced only moderate glucose and insulin responses, even though highly processed cereals were used. It is therefore recommended that a starch intake of <1.1 g/kg BW/meal or a meal size of 0.3 kg/100 kg BW (starch content of 30–40%) is used for horses.     

A Seroprevalence Study of Camel Brucellosis in Three Camel-rearing Regions of Ethiopia

A cross-sectional investigation was made into the seroprevalence of brucellosis in camels in three arid and semi-arid camel-rearing regions of Ethiopia (Afar, Somali and Borena) between November 2000 and April 2001. When sera collected from 1442 accessible camels were screened with the Rose Bengal plate test (RBPT), 82 (5.7%) of them reacted. The results of a complement fixation test (CFT) on those sera that had given a positive reaction to the screening test then indicated a 4.2% prevalence of brucellosis in the tested camels. There was a significant difference in the prevalence of brucellosis (² = 7.91, p<0.05), which was highest in Afar (5.2%) followed by Somali (2.8%) and Borena (1.2%) regions. Camels in Afar had a four times higher risk of brucellosis with an odds ratio (OR) of 4.34 (confidence interval, CI = 1.76–10.72, p<0.001) compared to the risk in Borena. Likewise, Afar had higher risk (OR = 1.76, 1.13–2.74, p<0.05) than that in Somali. There was no significant difference in seroprevalence between the sexes (p>0.05). Although a higher prevalence (6.3%) was observed in camels over 3 years old in Afar, there was no significant overall age difference (p>0.05).     

Disposition Kinetics and Urinary Excretion of Pefloxacin after Intravenous Injection in Crossbred Calves

The disposition kinetics and urinary excretion of pefloxacin after a single intravenous administration of 5 mg/kg were investigated in crossbred calves and an appropriate dosage regimen was calculated. At 1 min after injection, the concentration of pefloxacin in the plasma was 18.95±0.892 g/ml, which declined to 0.13±0.02 g/ml at 10 h. The pefloxacin was rapidly distributed from the blood to the tissue compartment as shown by the high values for the initial distribution coefficient, (12.1±1.21 h^–1) and the constant for the rate of transfer of drug from the central to the peripheral compartment, K ₁₂ (8.49±0.99 h^–1). The elimination half-life and volume of distribution were 2.21±0.111 h and 1.44±0.084 L/kg, respectively. The total body clearance (Cl_B) and the ratio of the drug present in the peripheral to that in the central compartment (P/C ratio) were 0.454±0.026 L/kg h) and 5.52±0.519, respectively. On the basis of the pharmacokinetic parameters obtained in the present study, an appropriate intravenous dosage regimen for pefloxacin in cattle for most of the bacteria sensitive to it would be 6.4 mg/kg repeated at 12 h intervals.     

Effects of Density and Water Availability on the Behavior, Physiology, and Weight Loss of Slaughter Horses during Transport

The aim of this study was to determine the effects of density and provision of water on aggressive behavior, stress, and weight loss in slaughter horses during transport. A 16.2-m, single deck semi-trailer was divided into three compartments to create high, medium, and low density (397 ± 6.5 kg/m², 348 ± 5.2 kg/m², and 221 ± 7.6 kg/m² per compartment) groups of unrestrained horses. Six shipments containing 23 to 30 horses per shipment were transported in June and July of 2004 for 18 to 20 hours. While the truck was stopped for 1 hour after 8 hours of transport and then again just before unloading, horses in each of two compartments received water for 1 hour from six water bowls (three bowls mounted on each side of a compartment). The third, non-watered compartment served as a control. Aggressive behavior of the horses was recorded using 12 video cameras installed in the trailer. All occurrences of aggressive behavior were counted from 15-minute segments of video during 2-hour intervals for each horse that was visible in each density group. Neither density nor water significantly affected (P > 0.21) aggressive behavior, cortisol, plasma chemistry profile, dehydration, or weight loss. Aggression did not differ (P = 0.49) between the first and second halves of the shipments, indicating that fatigue had not advanced to the stage where aggression was suppressed. Individual horses, rather than density were the major cause of aggressive behavior. However, two horses went down in the high density treatment, indicating that factors in high density could lead to increased morbidity or death.     

Pharmacological assessment of netobimin as a potential anthelmintic for use in horses: Plasma disposition, faecal excretion and efficacy

This study aimed to determine the plasma disposition and faecal excretion of netobimin (NTB) and its respective metabolites as well as the efficacy against strongyles in horses following oral administration. Netobimin (10 mg/kg) was administered orally to 8 horses. Blood and faecal samples were collected from 1 to 120 h post-treatment and analysed by high performance liquid chromatography (HPLC). Using a chiral phase-based HPLC, plasma disposition of ABZSO enantiomers produced was also determined. Faecal strongyle egg counts (EPG) were performed by a modified McMaster’s technique before and after the treatment. Neither NTB nor ABZ were present and only albendazole sulphoxide (ABZSO) and sulphone metabolites (ABZSO₂) were detected in the plasma samples. Maximum plasma concentration of ABZSO (0.53 ± 0.14 μg/ml) and ABZSO₂ (0.36 ± 0.09 μg/ml) were observed at (t_max) 10.50 and 19.50 h, respectively following administration of NTB. The area under the curve (AUC) of the two metabolites was similar to each other. Netobimin was not detected, and ABZ was predominant in faecal samples. The maximum plasma concentration (C_max) of (−)ABZSO was significantly higher than (+)ABZSO, but the area under the curves (AUCs) of the enantiomer were not significantly different each other in plasma samples. The enantiomers of ABZSO were close to racemate in the faecal samples analyzed. Netobimin reduced the EPG by 100%, 100%, 77%, 80% and 75% 2, 4, 6, 8 and 10 weeks post-treatment, respectively. The specific behaviour of the two enantiomers probably reflects different enantioselectivity of the enzymatic systems of the liver which are responsible for sulphoxidation and sulphonation of ABZ. Considering the pharmacokinetic and efficacy parameters NTB could be used as an anthelmintic in horses.     

喹赛多及其主要代谢物在猪体内的药代动力学研究

试验研究了灌服单剂量喹赛多(40 mg/kg体重)后原药及其代谢物在健康猪体内的药代动力学特征。液相色谱-串联质谱法测定血浆中喹赛多及其代谢物的浓度,通过WinNonlin 5.2药代动力学软件分析,用非房室模型统计矩原理计算喹赛多及其代谢产物的药动学参数。主要药动学参数分别为喹赛多:t_1/2 (7.52±1.77) h,C_max(0.02±0.01) μg/mL,AUC_{(0-36 h)} (0.26±0.24) (h·μg)/mL,MRT(11.37±3.21) h;N1(脱一氧喹赛多):t_1/2 (3.05±1.12) h,C_max(0.35±0.18) μg/mL,AUC_{(0-36 h)} (2.13±2.31) (h·μg)/mL,MRT(11.83±3.34) h。N4(脱一氧喹赛多):t_1/2 (2.91±1.15) h,C_max(0.60±0.32) μg/mL,AUC_{(0-36 h)} (3.78±4.28) (h·μg)/mL,MRT(11.00±2.86) h。脱二氧喹赛多:t_1/2 (3.85±1.30) h,C_max(0.46±0.19) μg/mL,AUC_{(0-36 h)} (4.21±2.47) (h·μg)/mL,MRT(13.35±2.65) h。QCA(喹口恶啉-2-羧酸):t_1/2 (5.08±0.57) h,C_max(0.25±0.11) μg/mL,AUC_{(0-36 h)} (3.05±1.46) (h·μg)/mL,MRT(15.15±1.83)h。结果表明,血浆中主要存在形式为代谢物,各代谢物的血药浓度及AUC_(0-∞)均高于喹赛多,喹赛多消除半衰期最长,QCA平均滞留时间最长。     

The disposition of theophylline in camels after intravenous administration

The pharmacokinetics of theophylline were determined after an intravenous (i.v.) dose of 2.36 mg/kg in six camels and 4.72 mg/kg body weight in three camels. The data obtained (median and range) for the low and high dose, respectively, were as follows: the distribution half-lives (t1/2 alpha) were 1.37 (0.64-3.25) and 2.66 (0.83-3.5) h, the elimination half-lives (t1/2 beta) were 11.8 (8.25-14.9) and 10.4 (10.0-13.5) h, the steady state volumes of distribution (Vss) were 0.88 (0.62-1.54) and 0.76 (0.63-0.76) L/kg, volumes of the central compartment (Vc) were 0.41 (0.35-0.63) and 0.51 (0.36-0.52) L/kg, total body clearances (Clt) were 62.3 (39.4-97.0) and 50.2 (47.7-67.4) mL/h.kg body weight and renal clearance (Vr) for the low dose was 0.6 (0.42-0.96) mL/h.kg body weight. There was no significant difference in the pharmacokinetic parameters between the two doses. Theophylline protein binding at a concentration of 5 micrograms/mL was 32.2 +/- 3.3%. Caffeine was identified as a theophylline metabolite but its concentration in serum and urine was small. Based on the pharmacokinetic values obtained in this study, a dosage of 7.5 mg/kg body weight administered by i.v. injection at 12 h intervals can be recommended. This dosing regimen should achieve an average steady state serum concentration of 10 micrograms/mL with peak serum concentration not exceeding 15 micrograms/mL.     

Single- and repeat-dose pharmacokinetic studies of chloramphenicol in horses: values and limitations of pharmacokinetic studies in predicting dosage regimens

A single-dose pharmacokinetic study of chloramphenicol in propylene glycol was done in 6 horses after 22 mg/kg was administered IV. Serum drug concentrations obtained at various predetermined intervals were determined by an electroncapture gas-chromatographic technique. The time-concentration data were described by a 2-compartment open model, and various pharmacokinetic variables were estimated. The median elimination rate constant was estimated to be -0.0185 minute-1 (-0.0225 to -0.0148 minute-1), and the median half-life was 37.36 minutes (30.74 to 46.90 minutes). The median apparent volume of distribution and total body clearance were 1.46 L/kg (1.13 to 1.60 L/kg) and 25.56 ml/kg/min (23.66 to 32.21 ml/kg/min), respectively. On the basis of these data, single- and repeat-dose kinetic studies were done in another group of 6 animals. The drug was administered at a dosage of 22 mg/kg every 4 hours for 3 days. Blood samples were obtained for pharmacokinetic studies after the first and the last doses were given. The half-life, volume of distribution, and total body clearance did not change significantly (Wilcoxon signed rank test) after 3 days of therapy with chloramphenicol. The IV dose schedule for treating bacterial infections with organisms of different sensitivities has been determined from the estimates of the pharmacokinetic variables. The limitations of calculating the dose schedules for chloramphenicol on the basis of pharmacokinetic variables in horses are discussed.     

Effect of dose of furosemide on plasma tCO2 changes in standardbred horses

Nine Standardbred horses of similar athletic fitness (six mares, three geldings), ranging from 4 to 11 years of age, were used to determine the effects of 0, 250, or 500 mg intravenously administered furosemide on plasma tCO₂ changes over time. All horses were either currently racing or in advanced stages of race training before entering a qualifying race. Horses were randomly allotted to one of the three treatment levels of furosemide during 3 consecutive weeks. Jugular venous samples were obtained from horses at rest in box stalls before and hourly for 6 hours after administration of furosemide. Body weights of horses ranged from 356 to 456 kg, and the mean was 417 kg. Thus, the dose of furosemide received by each horse ranged from 0.55 to 0.70 mg/kg body weight for the 250-mg injections and from 1.1 to 1.4 mg/kg body weight for the 500-mg injections. Furosemide caused metabolic alkalosis in the horses. Least square means (±SEM) were determined and horses had adjusted plasma tCO₂ of 32.2, 33.9, and 34.7 ± 0.41 for the 0-, 5-, and 10-mL doses of furosemide, respectively. The type 3 tests of hypotheses found that there was a difference (P < .0001) across time, a difference (P = .0016) according to furosemide dose, and a difference (P < .0001) according to treatment × hour. There was no difference (P > .05) according to week or treatment × week. These data suggest that either 250 or 500 mg furosemide given to Standardbred race horses induces statistically similar metabolic alkalosis.     

Comparative pharmacokinetics of norfloxacin nicotinate in common carp (Cyprinus carpio) and crucian carp (Carassius auratus) after oral administration

Comparative pharmacokinetics of norfloxacin nicotinate (NFXNT) was investigated in common carp (Cyprinus carpio) and crucian carp (Carassius auratus) after a single oral dose of 10 mg/kg body weight (b.w.). Analyses of plasma samples were performed using ultra‐performance liquid chromatography (UPLC) with fluorescence detection. After oral dose, plasma concentration–time curves of common carp and crucian carp were best described by a two‐compartment open model with first‐order absorption. The pharmacokinetic parameters of common carp were similar to those of crucian carp. The distribution half‐life (t_1/2α), elimination half‐life (t_1/2β), peak concentration (C_max), time‐to‐peak concentration (T_max), and area under the concentration–time curve (AUC) of common carp were 1.58 h, 26.33 h, 6069.79 μg/L, 1.08 h, and 103072.36 h·μg/L, respectively, and those corresponding to crucian carp were 1.36 h, 26.55 h, 9586.06 μg/L, 0.84 h, and 126604.4 h·μg/L, respectively. These studies demonstrated that 10 mg NFXNT/kg body weight in common carp and crucian carp following oral dose presented good pharmacokinetic characteristics.     

Pharmacokinetics and Pharmacodynamics of Dexamethasone after Intravenous Administration in Camels: Effect of Dose

The pharmacokinetics and pharmacodynamics of dexamethasone were evaluated in healthy camels after single intravenous bolus doses of 0.05, 0.1 and 0.2 mg/kg body weight. Dexamethasone showed dose-independent pharmacokinetics. The pharmacokinetic parameters of the two-compartment pharmacokinetic model for the lowest intravenous dose (mean+/-SD) were as follows: terminal elimination half-life 8.17 +/- 1.79 h; total body clearance 100.7 +/- 52.1 (ml/h)/kg; volume of distribution at steady state 0.95 +/- 0.23 L/kg; and volume of the central compartment 0.22 +/- 0.07 L/kg. The extent of plasma protein binding was linear over the concentration range 5-100 ng/ml and averaged 75% +/- 2%. Pharmacodynamic effects were evaluated by measuring endogenous plasma cortisol concentrations, numbers of circulating lymphocytes and neutrophils and plasma glucose concentrations and were analysed using indirect pharmacokinetic/pharmacodynamic models. The cumulative systemic effect increased with dose for markers of pharmacodynamic activity. The estimated IC50 of dexamethasone for cortisol and lymphocytes for the lowest dose were 3.74 +/- 2.44 and 5.58 +/- 8.37 ng/ml, respectively and the EC50 values for neutrophils and glucose were 45.8 +/- 36.9 and 1.17 +/- 0.71 ng/ml, respectively.     

Plasma and synovial fluid pharmacokinetics of a single intravenous dose of meropenem in adult horses

The objective of this study was to determine the pharmacokinetics of meropenem in horses after intravenous (IV) administration. A single IV dose of meropenem was administered to six adult horses at 10 mg/kg. Plasma and synovial fluid samples were collected for 6 hr following administration. Meropenem concentrations were determined by bioassay. Plasma and synovial fluid data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Mean ± SD values for elimination half‐life, volume of distribution at steady‐state, and clearance after IV administration for plasma samples were 0.78 ± 0.176 hr, 136.1 ± 19.69 ml/kg, and 165.2 ± 29.72 ml hr^‐1 kg^?1, respectively. Meropenem in synovial fluid had a slower elimination than plasma with a terminal half‐life of 2.4 ± 1.16 hr. Plasma protein binding was estimated at 11%. Based on a 3‐compartment open pharmacokinetic model of simultaneously fit plasma and synovial fluid, dosage simulations were performed. An intermittent dosage of meropenem at 5 mg/kg IV every 8 hr or a constant rate IV infusion at 0.5 mg/kg per hour should maintain adequate time above the MIC target of 1 μg/ml. Carbapenems are antibiotics of last resort in humans and should only be used in horses when no other antimicrobial would likely be effective.