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.     

The kinetic disposition and dosage regimen for carbenicillin in buffalo calves

The distribution half-life, elimination half-life, apparent volume of distribution and total body clearance of carbenicillin in healthy buffalo calves following a single intravenous administration (50 mg/kg) were 0.057±0.005 h, 1.688±0.11 h, 0.185±0.021 L kg^-1 and 75.97±6.519 ml kg^-1 h^-1 respectively. A satisfactory dosage regimen for carbenicillin in buffalo calves was calculated to be 56 mg/kg followed by 52 mg/kg body weight repeated at 6 h intervals.     

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.     

PK-PD integration and modeling of marbofloxacin in sheep

The fluoroquinolone antimicrobial drug, marbofloxacin, was administered intravenously (IV) and intramuscularly (IM) to sheep at a dose rate of 2 mg kg⁻¹ in a 2-period cross-over study. Using a tissue cage model of inflammation, the pharmacokinetic properties of marbofloxacin were established for serum, inflamed tissue cage fluid (exudate) and non-inflamed tissue cage fluid (transudate). For serum, after IV dosing, mean values for pharmacokinetic parameters were: clearance 0.48 L kg⁻¹ h⁻¹; elimination half-life 3.96 h and volumes of distribution 2.77 and 1.96 L kg⁻¹, respectively, for V_darea and V_ss. After IM dosing mean values for pharmacokinetic variables were: absorption half-time 0.112 h, time of maximum concentration 0.57 h, terminal half-life (T½el) 3.65 h and bioavailability 106%. For exudate, mean T½el values were 12.38 and 13.25 h, respectively, after IV and IM dosing and for transudate means were 13.39 h (IV) and 12.55 h (IM).The in vitro minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) and ex vivo time-kill curves for marbofloxacin in serum, exudate and transudate were established against a pathogenic strain of Mannheimia haemolytica. Integration of in vivo pharmacokinetic data with MIC determined in vitro provided mean values of area under curve (AUC)/MIC ratio for serum, exudate and transudate of 120.2, 156.0 and 156.6 h after IV dosing and 135.5, 165.3 and 146.2 h after IM dosing, respectively. After IM administration maximum concentration (C_max)/MIC ratios were 21.1, 6.76 and 5.91, respectively, for serum, exudate and transudate. The ex vivo growth inhibition data after IM administration were fitted to the sigmoid E_max (Hill) equation to provide values for serum of AUC_24 h/MIC producing, bactericidal activity (22.51 h) and virtual eradication of bacteria (35.31 h). It is proposed that these findings might be used with MIC₅₀ or MIC₉₀ data to provide a rational approach to the design of dosage schedules which optimise efficacy in respect of bacteriological as well as clinical cures.     

Pharmacokinetics of lincomycin following single intravenous administration in buffalo calves

Lincomycin 10 mg kg^?1, IV in buffalo calves followed two-compartment open model with high distribution rate constant α (11.2?±?0.42 h^?1) and K ₁₂/K ₂₁ ratio (4.40?±?0.10). Distribution half-life was 0.06?±?0.01 h and AUC was 41.6?±?1.73 μg mL^?1 h. Large Vd_area (1.15?±?0.03 L kg^?1) indicated good distribution of lincomycin in various body fluids and tissues. Peak plasma level of lincomycin (71.8?±?1.83 μg mL^?1) was observed at 1 min as expected by IV route. The elimination half-life and MRT of lincomycin were short (3.30?±?0.08 and 4.32?±?0.11 h, respectively). Lincomycin 10 mg kg^?1 IV at 12-h interval would be sufficient to maintain T?>?MIC above 60 % for bacteria with minimum inhibitory concentrations (MIC) values ≤1.6 μg mL^?1. Favourable pharmacokinetic profile in buffalo calves and a convenient dosing interval suggest that lincomycin may be an appropriate antibacterial in buffalo species for gram-positive and anaerobic bacterial pathogens susceptible to lincomycin.     

Pharmacokinetic and pharmacodynamic interactions of tolfenamic acid and marbofloxacin in goats

Pharmacokinetic and pharmacodynamic properties in goats of the non-steroidal anti-inflammatory drug tolfenamic acid (TA), administered both alone and in combination with the fluoroquinolone marbofloxacin (MB), were established in a tissue cage model of acute inflammation. Both drugs were injected intramuscularly at a dose rate of 2 mg kg⁻¹. After administration of TA alone and TA + MB pharmacokinetic parameters of TA (mean values) were C_max = 1.635 and 1.125 μg ml⁻¹, AUC = 6.451 and 3.967 μg h ml⁻¹, t_1/2K₁₀ = 2.618 and 2.291 h, Vdarea/F = 1.390 and 1.725 L kg⁻¹, and ClB/F = 0.386 and 0.552 L kg⁻¹ h⁻¹, respectively. These differences were not statistically significant. Tolfenamic acid inhibited prostaglandin (PG)E₂ synthesis in vivo in inflammatory exudate by 53-86% for up to 48 h after both TA treatments. Inhibition of synthesis of serum thromboxane (Tx)B₂ ex vivo ranged from 16% to 66% up to 12 h after both TA and TA + MB, with no significant differences between the two treatments.From the pharmacokinetic and eicosanoid inhibition data for TA, pharmacodynamic parameters after dosing with TA alone for serum TxB₂ and exudate PGE₂ expressing efficacy (E_max = 69.4 and 89.7%), potency (IC₅₀ = 0.717 and 0.073 μg ml⁻¹), sensitivity (N = 3.413 and 1.180) and equilibration time (t_1/2K_e0 = 0.702 and 16.52 h), respectively, were determined by PK-PD modeling using an effect compartment model. In this model TA was a preferential inhibitor of COX-2 (COX-1:COX-2 IC₅₀ ratio = 12:1). Tolfenamic acid, both alone and co-administered with MB, did not affect leucocyte numbers in exudate, transudate or blood. Compared to placebo significant attenuation of skin temperature rise over inflamed tissue cages was obtained after administration of TA and TA + MB with no significant differences between the two treatments. Marbofloxacin alone did not significantly affect serum TxB₂ and exudate PGE₂ concentrations or rise in skin temperature over exudate tissue cages. These data provide a basis for the rational use of TA in combination with MB in goat medicine.     

Effect of ractopamine hydrochloride and zilpaterol hydrochloride on growth,diet digestibility,intake and carcass characteristics of feedlot lambs

The effects of the β-adrenergic agonists ractopamine hydrochloride (RH; 0.35, 0.70 and 1.05 mg kg^− 1 of BW d^− 1) and zilpaterol hydrochloride (ZH; 0.10, 0.20 and 0.30 mg kg^− 1 of BW d^− 1) on growth performance and carcass characteristics were determined in 84 Dorper × Katahdin lambs (12 lambs per treatment), that were randomly assigned to a complete block design during a 42-day feeding trial. Lambs were fed a corn grain-based diet (18.71% CP and 12.9 MJ/kg ME). Nutrient digestibility of diets and blood serum metabolites were also determined. There were no significant (P > 0.05) differences in growth characteristics by effect of ZH or RH administration. However, lambs final weight, total weight gain and ADG increased linearly (P < 0.05) as levels of both β-adrenergic agonist increased. RH or ZH administration did not affect feed efficiency, diet digestibility or particular blood serum metabolites of lambs. Carcass characteristics of lambs consuming ZH were significantly better (P < 0.01) than RH or control lambs; RH produced significant linear response on carcass weight, dressing percentage, longissimus muscle area, carcass conformation and quality grade, and improved quadratically (P < 0.05) fat thickness and USDA yield grade of lamb carcasses. On the other hand, increasing levels of ZH decreased linearly (P > 0.01) fat thickness and improved (P > 0.05) USDA yield grade and carcass quality grade. Both β-adrenergic agonists improved carcass characteristics; although greater improvements were obtained with ZH than RH for most carcass characteristics.     

Pharmacokinetics of oxytetracycline after intramuscular administration with lidocaine in sheep, comparison with a conventional formulation

The pharmacokinetic behaviour of oxytetracycline (OTC) was studied in 11 sheep after intravenous and intramuscular administration at a single dosage of 20 mg kg⁻¹ bodyweight. A conventional formulation was injected by the intravenous route and two different preparations were administered by the intramuscular route: a conventional formulation (T-100) and an aqueous solution of OTC with lidocaine (1 per cent) (OTC-Q. The objective was to determine whether there are differences between both formulations in the disposition kinetics of OTC after intramuscular administration to sheep. After intravenous administration of the conventional formulation, plasma oxytetracycline concentrations were best fitted to an open two-compartment model. Mean apparent volume of distribution was 0·77±0·02 litre kg⁻¹ and the harmonic mean half-life was three hours. The OTC transfer process between central and peripheral compartments was fast and that did not influence the elimination process. After intramuscular administrations of both formulations, half-lives were longer than after intravenous administration (mean values of 14·1 and 58·2 hours for T-100 and OTC-L respectively). In both cases, a biphasic absorption, a ‘flip-flop’ model and a complete bioavailability were found. OTC-L provided therapeutic plasma concentrations over 0·5 μg ml⁻¹ (the minimum inhibitory concentration for most susceptible pathogens) for a longer period of time than T-100 (72 hours compared with 36 or 48 hours).     

Anthelmintic activity of Cocos nucifera L. against sheep gastrointestinal nematodes

The development of anthelmintic resistance has made the search for alternatives to control gastrointestinal nematodes of small ruminants imperative. Among these alternatives are several medicinal plants traditionally used as anthelmintics. This work evaluated the efficacy of Cocos nucifera fruit on sheep gastrointestinal parasites. The ethyl acetate extract obtained from the liquid of green coconut husk fiber (LGCHF) was submitted to in vitro and in vivo tests. The in vitro assay was based on egg hatching (EHT) and larval development tests (LDT) with Haemonchus contortus. The concentrations tested in the EHT were 0.31, 0.62, 1.25, 2.5 and 5 mg ml⁻¹, while in the LDT they were 5, 10, 20, 40 and 80 mg ml⁻¹. The in vivo assay was a controlled test. In this experiment, 18 sheep infected with gastrointestinal nematodes were divided into three groups (n = 6), with the following doses administered: G1—400 mg kg⁻¹ LGCHF ethyl acetate extract, G2—0.2 mg kg⁻¹ moxidectin (Cydectin^®) and G3—3% DMSO. The worm burden was analyzed. The results of the in vitro and in vivo tests were submitted to ANOVA and analyzed by the Tukey and Kruskal–Wallis tests, respectively. The extract efficacy in the EHT and LDT, at the highest concentrations tested, was 100% on egg hatching and 99.77% on larval development. The parameters evaluated in the controlled test were not statistically different, showing that despite the significant results of the in vitro tests, the LGCHF ethyl acetate extract showed no activity against sheep gastrointestinal nematodes.     

Disposition and dosage regimen of cephaloridine in calves

The disposition and dosage regimen of cephaloridine were investigated in healthy calves following a single intramuscular administration of 10 mg/kg. The absorption halflife, climination halflife, apparent volume of distribution and total body clearance were 0.107±0.025 h, 2.08±0.14 h, 0.70±0.07L kg^-1 and 235.8±21.9 ml kg^-1 h^-1, respectively. Therapeutic plasma levels (1 g/ml) were maintained for up to 7 h. A satisfactory intramuscular dosage regimen for cephaloridine in calves would be 10 mg/kg repeated at 8 h intervals.     

Pharmacokinetics of enrofloxacin and danofloxacin in premature calves

The aim of this study was to determine the pharmacokinetics/pharmacodynamics of enrofloxacin (ENR) and danofloxacin (DNX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. The study was performed on twenty‐four calves that were determined to be premature by anamnesis and general clinical examination. Premature calves were randomly divided into four groups (six premature calves/group) according to a parallel pharmacokinetic (PK) design as follows: ENR‐IV (10 mg/kg, IV), ENR‐IM (10 mg/kg, IM), DNX‐IV (8 mg/kg, IV), and DNX‐IM (8 mg/kg, IM). Plasma samples were collected for the determination of tested drugs by high‐pressure liquid chromatography with UV detector and analyzed by noncompartmental methods. Mean PK parameters of ENR and DNX following IV administration were as follows: elimination half‐life (t_1/2λz) 11.16 and 17.47 hr, area under the plasma concentration–time curve (AUC_0‐48) 139.75 and 38.90 hr*µg/ml, and volume of distribution at steady‐state 1.06 and 4.45 L/kg, respectively. Total body clearance of ENR and DNX was 0.07 and 0.18 L hr^?1 kg^?1, respectively. The PK parameters of ENR and DNX following IM injection were t_1/2λz 21.10 and 28.41 hr, AUC_0‐48 164.34 and 48.32 hr*µg/ml, respectively. The bioavailability (F) of ENR and DNX was determined to be 118% and 124%, respectively. The mean AUC_0‐48CPR/AUC_0‐48ENR ratio was 0.20 and 0.16 after IV and IM administration, respectively, in premature calves. The results showed that ENR (10 mg/kg) and DNX (8 mg/kg) following IV and IM administration produced sufficient plasma concentration for AUC_0‐24/minimum inhibitory concentration (MIC) and maximum concentration (C_max)/MIC ratios for susceptible bacteria, with the MIC₉₀ of 0.5 and 0.03 μg/ml, respectively. These findings may be helpful in planning the dosage regimen for ENR and DNX, but there is a need for further study in naturally infected premature calves.     

The inhibition of experimentally induced visceral hyperalgesia by nifedipine - a voltage-gated Ca(2+) channels blocker (VGCCs) in sheep

Present study examined the effect of VGCC L-type blocker - nifedipine given i.c.v. (0.25, 0.5, 1 and/or 2 mg in toto) on the development of nociceptive behavior, clinical symptoms, plasma catecholamin concentration and reticulo-rumen motility following 5 min lasting mechanical duodenal distension (DD) in sheep. After 24 h of fasting, all animals received i.m. ketamine analgesia (20 mg kg⁻¹ B.W) and anesthetized with pentobarbital (20 mg kg⁻¹ B.W., i.v. infusion) The permanent stainless steel cannula 29 mm in length and 2 mm in diameter was inserted into the lateral cerebral ventricle (controlled by cerebro-spinal efflux) 10 mm above the bregma and 5 mm laterally from the midline sutures using stereotaxic method.Under the same general anesthesia/analgesia a T-shaped silicon cannula (inside diameter of 21 mm), was inserted into the duodenum (12 cm from pylorus). Second identical cannule was inserted into the dorsal sac of the rumen, a previously described. After surgery each animal was kept in individual boxes for 10 days prior to experiment and was treated i.m. with benzyl procaine penicillin 30,000 I.U kg⁻¹ B.W.) + dihydrostreptomycine sulfate (10 g kg⁻¹ B.W.) + prednisolone acetate (1.2 mg kg⁻¹ B.W.) combination and i.m. ketamine (20 mg kg⁻¹ B.W.) every day by seven consecutive days.Experimental DD was conducted by insertion and then distension of rubber balloon (containing 40 ml of warm water) inserted into sheep duodenum. Duodenal distension produced a significant increase in behavioral pain manifestations, tachycardia, hyperventilation, inhibition of reticulo-ruminal contractions rate (from 87.2 to 38.0% during 15-20 min), an increase of plasma catecholamine concentration (over 6.4-fold increase of epinephrine during 2 h following DD, 2-times norepinephrine and 84% increase of dopamine). Nifedipine infusion administered 10 min prior to DD decreased intensity of visceral pain manifestations such as: behavioral changes, hyperventilation, reticulo-rumen motility and efficiently prevent appearance of catecholamine release. These data demonstrated that the development and persistence of duodenal hyperalgesia depends on the activation of Ca²⁺ ion flux leading to neurotransmitters release and modulation of membrane excitability. It seems that nifedipine given i.c.v. 10 min prior to DD (as a source of visceral pain), inhibited specific receptors 1 subunits of VGCCs in target tissues, prevented depolarization of cell membranes and release of neurotransmitters responsible for pain sensitivity in sheep. The observed antinociceptive action of VGCCs type L blockers suggest that these channels play a crucial role in the modulation of acute visceral hyperalgesia in sheep.     

Disposition kinetics and urinary excretion of gentamicin in buffalo bulls (Bubalus bubalis)

The disposition kinetics and urinary excretion of gentamicin sulphate were studied in young buffalo bulls following a single intramuscular administration of the drug at 5 mg kg^-1 body weight. The time course of the serum gentamicin concentration was adequately described by the one-compartment open model. The values of the absorption and elimination halflives were 12.2±2.2 and 167.0±29.7 min respectively. The apparent volume of distribution was 0.29±0.01 L kg^-1. During the first 12 h, 63% of the total administered dose was excreted in urine. On the basis of the kinetic data, a satisfactory intramuscular dosage regimen for gentamicin sulphate would be at least 6 mg kg^-1 body weight repeated at 8 h intervals.     

A comparison of the effects of hydromorphone HCl and a novel extended release hydromorphone on arterial blood gas values in conscious healthy dogs

The purpose of this study was to evaluate arterial blood gases in dogs that were given hydromorphone or extended release liposome-encapsulated hydromorphone (LEH). Dogs were randomly administered LEH, n = 6, (2.0 mg kg⁻¹), hydromorphone, n = 6, (0.2 mg kg⁻¹) or a placebo of blank liposomes, n = 3, subcutaneously on separate occasions. Arterial blood samples were drawn at serial time points over a 6-h time period for blood gas analysis. There was no change from baseline values in P_aCO₂, P_aO₂, (HCO₃-), pH, and SBEc in the dogs that received the placebo. Administration of hydromorphone resulted in significant increases in P_aCO₂ (maximum (mean + SD] 44.4 + 1.1 mm of Hg) and significant decreases in P_aO₂ (minimum (mean + SD) 82.4 + 4.7 mm of Hg) and pH (minimum (mean + SD) 7.31 + 0.01) compared with baseline. Administration of LEH resulted in significant increases in P_aCO₂ (maximum (mean + SD) 44.6 + 0.9 mm of Hg) and significant decreases in P_aO₂ (minimum (mean + SD) 84.8 + 2.6 mm of Hg) and pH (minimum (mean + SD) 7.34 + 0.02) compared with baseline. There was no significant difference between these two groups at any time point. The changes observed in P_aCO₂, P_aO₂, and pH, however, were within clinically acceptable limits for healthy dogs. LEH was determined to cause moderate changes in arterial blood gas values similar to those caused by hydromorphone.     

Comparative pharmacokinetics and pharmacokinetic/pharmacodynamic analysis by nonlinear mixed‐effects modeling of cefquinome in nonpregnant,pregnant, and lactating goats after intravenous and intramuscular administration

Cefquinome is a fourth‐generation cephalosporin that is used empirically in goats. Different physiologic factors like pregnancy or lactation could determine the pharmacokinetic behavior of drugs in the organism. The objectives of this study are to (a) compare the pharmacokinetics of cefquinome after intravenous and intramuscular administration in adult nonpregnant (n = 6), pregnant (n = 6), and lactating goats (n = 6), at a dose of 2 mg/kg, with rich sampling by nonlinear mixed‐effects modeling, (b) conduct a pharmacokinetic/pharmacodynamic analysis to evaluate the efficacy of the recommended posology in goats with different physiological states, and (c) determine the optimal posology that achieve a PTA value ≥ 90%, taking into account a T > MIC ≥ 60% of a MIC value ≤ 0.25 µg/ml, in the different subpopulations of goats for both routes. Gestation significantly increased Ka and V1, while reduced F0, Cl, and Q. On the other hand, lactation significantly increased V1 and reduced Tk0. Cefquinome concentrations achieved in placental cotyledon, amniotic fluid, and fetal serum indicate a minimal penetration across the placental barrier. Moreover, milk penetration of cefquinome was minimal. The total body clearance of cefquinome for goats was 0.29 L kg^?1 hr^?1, that is apparently higher than the reported for cows (0.13 L kg^?1 hr^?1) and pigs (0.16 L kg^?1 hr^?1). So, the optimal dose regimen for cefquinome after intravenous and intramuscular administration required higher dose and frequency of administration compared with recommendations for cows or pigs. Therefore, 2 mg kg^?1 8 hr^?1 and 5 mg kg^?1 12 hr^?1 could be used for IV and IM routes, respectively, for the treatment of respiratory infections caused by P. multocida and M. haemolytica, but only 5 mg kg^?1 12 hr^?1 by both routes should be recommended for Escherichia coli infections.     

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     

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.     

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.     

Comparative evaluation of sedative and clinical effects of dexmedetomidine and xylazine in dromedary calves (Camelus dromedarius)

ObjectiveTo compare the sedative and clinical effects of intravenous (IV) administration of dexmedetomidine and xylazine in dromedary calves.Study designExperimental, crossover, randomized, blinded study.AnimalsA total of seven healthy male dromedary calves aged 14 ± 2 weeks and weighing 95 ± 5.5 kg.MethodsCalves were assigned three IV treatments: treatment XYL, xylazine (0.2 mg kg⁻¹); treatment DEX, dexmedetomidine (5 μg kg⁻¹); and control treatment, normal saline (0.01 mL kg⁻¹). Sedation scores, heart rate (HR), respiratory rate (f_R), rectal temperature (RT) and ruminal motility were recorded before (baseline) and after drug administration. Sedation signs were scored using a 4-point scale. One-way anova and Mann–Whitney U tests were used for data analysis.ResultsCalves in treatments XYL and DEX were sedated at 5–60 minutes. Sedation had waned in XYL calves, but not DEX calves, at 60 minutes (p = 0.037). Sedation was not present in calves of any treatment at 90 minutes. HR decreased from baseline in XYL and DEX at 5–90 minutes after drug administration and was lower in DEX than XYL at 5 minutes (p = 0.017). HR was lower in DEX (p = 0.001) and XYL (p = 0.013) than in control treatment at 90 minutes. f_R decreased from baseline in XYL and DEX at 5–60 minutes after drug administration and was lower in DEX than XYL at 5 minutes (p = 0.013). RT was unchanged in any treatment over 120 minutes. Ruminal motility was decreased in XYL at 5, 90 and 120 minutes and absent at 10–60 minutes. Motility was decreased in DEX at 5, 10 and 120 minutes and was absent at 15–90 minutes.Conclusion and clinical relevanceThe duration of sedation from dexmedetomidine (5 μg kg^–1) and xylazine (0.2 mg kg^–1) was similar in dromedary calves.     

Intravenous pharmacokinetics of moxifloxacin following simultaneous administration with flunixin meglumine or diclofenac in sheep

In this study, the pharmacokinetics of moxifloxacin (5 mg/kg) was determined following a single intravenous administration of moxifloxacin alone and co-administration with diclofenac (2.5 mg/kg) or flunixin meglumine (2.2 mg/kg) in sheep. Six healthy Akkaraman sheep (2 ± 0.3 years and 53.5 ± 5 kg of body weight) were used. A longitudinal design with a 15-day washout period was used in three periods. In the first period, moxifloxacin was administered by an intravenous (IV) injection. In the second and third periods, moxifloxacin was co-administered with IV administration of diclofenac and flunixin meglumine, respectively. The plasma concentration of moxifloxacin was assayed by high-performance liquid chromatography. The pharmacokinetic parameters were calculated using a two-compartment open pharmacokinetic model. Following IV administration of moxifloxacin alone, the mean elimination half-life (t_1/2β), total body clearance (Cl_T), volume of distribution at steady state (V_dss) and area under the curve (AUC) of moxifloxacin were 2.27 hr, 0.56 L h⁻¹ kg⁻¹, 1.66 L/kg and 8.91 hr*µg/ml, respectively. While diclofenac and flunixin meglumine significantly increased the t_1/2β and AUC of moxifloxacin, they significantly reduced the Cl_T and V_dss. These results suggest that anti-inflammatory drugs could increase the therapeutic efficacy of moxifloxacin by altering its pharmacokinetics.