Pharmacokinetic profile of cefotaxime in goats

Cefotaxime was administered to goats intravenously, intramuscularly and subcutaneously to determine blood and urine concentration, kinetic behaviour and bioavailability. Following a single intravenous injection, the blood concentration-time curve indicated a two compartment open model, with an elimination half-life value (t1/2 beta) of 22.38 +/- 0.41 minutes. Both intramuscular and subcutaneous routes showed slower values, that is, 38.64 and 69.58 minutes. The apparent volume of distribution of cefotaxime in goats was less than 1 litre kg-1 and suggested a lower distribution in tissues than in blood. After intramuscular and subcutaneous injections peak plasma cefotaxime concentrations were 77.8 +/- 1.7 and 44.0 +/- 0.8 micrograms ml-1 at 29.6 and 40.4 minutes, respectively. The average bioavailability of cefotaxime given by intramuscular and subcutaneous injection was 1.08 and 1.25 times the intravenous availability, respectively. The cefotaxime concentration remained in urine 24 hours longer after subcutaneous injection than after intramuscular administration.     

Pharmacokinetic profile of cefotaxime in goats

Cefotaxime was once administered in goats via intravenous, intramuscular and subcutaneous routes for determination of blood and urine concentration, kinetic behaviour and bioavailability. Following a single intravenous injection, the blood concentration-time curve indicated two compartments open model, with an elimination half-life value (t1/2 beta) of 22.38 +/- 0.41 minutes. Both intramuscular and subcutaneous routes showed lower values i.e. 38.64 and 69.58 minutes. The lower apparent volume of distribution of cefotaxime in goats than one liter/kg elucidated lower distribution in tissues than in blood. After intramuscular and subcutaneous injections peak plasma cefotaxime concentrations were 77.8 +/- 1.7 and 44.0 +/- 0.8 micrograms/ml at 29.6 and 40.4 minutes, respectively. The average bioavailability of cefotaxime given by intramuscular and subcutaneous injection was 1.08 and 1.25, respectively. The cefotaxime concentration remained in urine 24 hours longer after subcutaneous injection than after intramuscular administration.     

Disposition kinetics of florfenicol in goats by using two analytical methods

Florfenicol, a monofluorinated analogue of thiamphenicol, has antibacterial activity against a broad spectrum of bacterial strains, including enteric bacteria that are resistant to chloramphenicol and thiamphenicol. The pharmacokinetics of florfenicol was studied following a single intravenous bolus or intramuscular injections at a dose of 20 mg/kg body weight, in five healthy goats. Serum florfenicol concentrations were determined using two analytical methods: microbiological assay and high-performance liquid chromatography (HPLC). Pharmacokinetic analysis was performed using redundant routine equations and the results derived from each method were compared. While florfenicol was detected for up to 4 and 8 h after administration by the bioassay, the drug was recovered in serum after 12 and 24 h by HPLC following intravenous and intramuscular injections, respectively. Comparison of the concentration profiles obtained by the two methods revealed substantial differences in the resultant kinetic data. Values for the initial serum concentration, elimination half-life, the area under the serum concentration-time curve, the mean residence time, and the systemic bioavailability were significantly (P < 0.01) higher when florfenicol concentrations were determined using HPLC. In conclusion, differences between analytical methodologies should be considered when interpreting the kinetic data for clinical use. However, both the hepatic biotransformations and the interchangeability of enantiomers need further investigation.     

复方氟苯尼考注射液在猪体内的药代动力学研究

本文对自制氟苯尼考(FF)和氟尼辛葡甲胺(FM)复方制剂在猪体内的药代动力学进行了研究。试验选用健康断奶仔猪6头(30±5 kg),采用三周期交叉设计。FF给药剂量均为20 mg/kg体重。FM给药剂量均为2 mg/kg体重(以氟尼辛计),同一头猪不同给药的时间间隔为2周,给药途径均为颈部肌肉注射。试验结果显示,自制复方制剂与两种进口市售单方制剂在动物体内的药代过程基本一致,氟苯尼考和氟尼辛葡甲胺相对生物利用度分别为99.89%和108.78%,表明本复方注射液中两种药物的药效均与国外进口单方产品相当。一次给药即可获得两种进口单方制剂同时给药的良好疗效,且具有方便临床给药、减少动物应激的显著优点。     

“一针肥”注射液中硒元素在山羊体内的药代动力学研究

为研究＂一针肥＂注射液中硒元素在山羊体内的血硒水平及药动学变化规律,采用单剂量肌肉注射＂一针肥＂注射液0.2mL/kg（相当于硒用量6μg/kg）,用原子荧光法测定血硒浓度,通过3p97药物动力学程序软件分析药时数据。结果显示,肌注＂一针肥＂注射液后,血硒的药时数据符合二室开放模型,主要的药代动力学参数分别为：t1/2Ka（0.148 4±0.051 0）h,t1/2α（6.832 4±0.397 7）h,t1/2β（362.324 3±17.789 5）h,Kel（0.004 3±0.000 3）h,AUC（22 414.233 5±2 512.959 8）（μg/L）.h。结果表明,肌注＂一针肥＂注射液后硒在山羊体内吸收迅速,消除缓慢。     

Induction of estrus during the non-breeding season in Egyptian Baladi goats

The induction of estrus during the non-breeding season was investigated in 100 Egyptian Baladi goats (Capra hircus). All animals assigned to treatments had low progesterone concentrations (<0.5 ng/ml) tested 2 times 10 days apart to confirm anestrous condition. Animals were assigned to three experimental groups. A group of animals received subcutaneous norgestomet ear implant for 11 days and a single i.m. injection of PGF2alpha 24 hr before implant removal (group I; n=40). Second group of animals received subcutaneous norgestomet ear implant for 11 days and a single i.m. injection of PGF2alpha 24 hr before implant removal and gonadotropin releasing hormone 24 hr after implant removal (group II; n=40). Third group of animals received no treatment (control group; n=20). The percentage of goats that showed estrous behavior during the first 72 hr after implant removal was 77.5, 85.0% and 10.0% in group I, group II and control group, respectively. The fertility rate was 57.5, 70.0% and 10.0% in group I, group II and control group, respectively. In conclusion, estrus can be induced in seasonally anestrous Egyptian Baladi goats using norgestomet and PGF2alpha and the injection of GnRH 24 hr after norgestomet implant removal synchronized ovulation in a higher percentage of goats.     

Oxfendazole--anthelmintic activity in Egyptian goats artificially infected with gastrointestinal nematodes.

The recently developed benzimidazole anthelmintic, oxfendazole, was tested against artificial nematode infestations in Egyptian goats using oral dosing at 4.5 and 2.8 mg/kg. A 100% clearance of mature and immature Haemonchus contortus, Trichostrongylus axei, Ostertagia circumcincta, Coopera curticei, Bunostomum trigonocephalum and Chabertia ovina was obtained at the 4.5 mg/kg level. Very high levels of clearance against the mature worms were obtained at 2.8 mg/kg but the drug was less effective against immature worms at the lower dose rate. PCV, hemoglobin concentration and total erythrocyte counts declined after infection but became significantly (P less than 0.001) raised in treated animal.     

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.     

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.     

Pharmacokinetic comparison of six anthelmintics in sheep,goats, and cattle

This study was initiated to determine whether a comparative pharmacokinetic (PK) approach could be used to expand the pool of approved anthelmintics for minor ruminant species. Accordingly, the PK profiles of six anthelmintics (levamisole, albendazole, fenbendazole, moxidectin, doramectin, and ivermectin) in sheep, goats, and cattle were determined. The PK values determined for each anthelmintic included T_max, T_last, C_max, AUC, AUC/dose, and C_max/dose. The results of this study demonstrate that a comparative PK approach does not show commonality in the way these six anthelmintics are individually processed by these three ruminants. While some drugs demonstrated identical PK profiles between sheep and goats, none of these drugs demonstrated PK profiles in sheep and goats comparable to the PK profiles found in cattle. The results from this study suggest drug approval across these three ruminants is not a viable concept. However, the resulting PK profiles for each combination of drug and ruminant species represents a new dataset that can be used to support the US FDA Center for Veterinary Medicine's Minor Use/Minor Species indexing process for drug approvals in minor species such as sheep and goats.     

Pathogenicity of peste des petits ruminants virus isolated from Egyptian goats in Egypt

2 Egyptian goats and Boscat rabbits were experimentally inoculated with peste des petits ruminants (PPR) local Egyptian strain (PPR, Egypt 87). The inoculated animals contracted the disease with minor clinical manifestations, accompanied by rise of neutralizing antibodies to PPR virus. Virus was isolated from ocular and nasal secretions, buffy coat, spleen, and liver. No contact infection was observed between inoculated and healthy goats.     

Pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in adult goats

The pharmacokinetic behavior of marbofloxacin was studied in goats after single-dose intravenous (i.v.) and intramuscular (i.m.) administrations of 2 mg/kg bodyweight. Drug concentration in plasma was determined by high performance liquid chromatography (HPLC) and the data collected were subjected to compartmental and noncompartmental kinetic analysis. This compound presented a relatively high volume of distribution (Vss=1.31 L/kg), which suggests good tissue penetration, and a total body clearance (Cl) of 0.23 L/kg small middle doth, which is related to a long elimination half-life (t1/2beta=7.18 h and 6.70 h i.v. and i.m., respectively). Pharmacokinetic parameters were not significantly different between both routes of administration. Marbofloxacin was rapidly absorbed after i.m. administration (Tmax=0.9 h) and had high bioavailability (F=100.74%).     

高效液相法测定复方氟苯尼考注射液中氟苯尼考的含量

建立了测定氟苯尼考注射液中氟苯尼考含量的高效液相色谱法。采用C18色谱柱（4.6 mm×150 mm,5μm）,流动相为甲醇∶水（pH值为3.0）为40∶60（v/v）,流速为1 mL/min,检测波长为222 nm,进样10μL,柱温为室温。氟苯尼考浓度在0.1-3 mg/mL范围内,峰面积与浓度的线性关系良好（R^2=0.999 6）;平均回收率为99.49%,RSD为1.12%（n=4）。此法简便、快速、灵敏度高、重现性好。     

Pharmacokinetic properties of enrofloxacin in rabbits.

The pharmacokinetic properties of the fluoroquinolone antimicrobial enrofloxacin were studied in New Zealand White rabbits. Four rabbits were each given enrofloxacin as a single 5 mg/kg of body weight dosage by IV, SC, and oral routes over 4 weeks. Serum antimicrobial concentrations were determined for 24 hours after dosing. Compartmental modeling of the IV administration indicated that a 2-compartment open model best described the disposition of enrofloxacin in rabbits. Serum enrofloxacin concentrations after SC and oral dosing were best described by a 1- and 2-compartment model, respectively. Overall elimination half-lives for IV, SC, and oral routes of administration were 2.5, 1.71, and 2.41 hours, respectively. The half-life of absorption for oral dosing was 26 times the half-life of absorption after SC dosing (7.73 hours vs 0.3 hour). The observed time to maximal serum concentration was 0.9 hour after SC dosing and 2.3 hours after oral administration. The observed serum concentrations at these times were 2.07 and 0.452 micrograms/ml, respectively. Mean residence times were 1.55 hours for IV injections, 1.46 hours for SC dosing, and 8.46 hours for oral administration. Enrofloxacin was widely distributed in the rabbit as suggested by the volume of distribution value of 2.12 L/kg calculated from the IV study. The volume of distribution at steady-state was estimated at 0.93 L/kg. Compared with IV administration, bioavailability was 77% after SC dosing and 61% for gastrointestinal absorption. Estimates of predicted average steady-state serum concentrations were 0.359, 0.254, and 0.226 micrograms/ml for IV, SC, and oral administration, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetic behavior and pharmacokinetic/pharmacodynamic integration of marbofloxacin after subcutaneous administration in goats

The pharmacokinetic behavior of marbofloxacin was studied in goats after single-dose subcutaneous (SC) administration of 2mg/kg bodyweight. Drug concentration in plasma was determined by high performance liquid chromatography and the data obtained were subjected to non-compartmental kinetic analysis. Marbofloxacin peak plasma concentration (C(max)=1.77+/-0.24microg/mL) was reached 1.25+/-0.50h (T(max)) after SC administration. The elimination half-life (t(1/2beta)) and area under curve (AUC) were 5.74+/-1.21h and 8.15 vs 2.33microg h/mL, respectively. Taking into account the values obtained for the efficacy indices, it was concluded that a SC dose of 2mg/kg/24h of marbofloxacin could be adequate to treat infections caused by high susceptible bacteria like Escherichia coli or Salmonella spp.     

Pharmacokinetic data on doxycycline and its distribution in different biological fluids in female goats

A pharmacokinetic study of doxycycline after intravenous administration at 5 mg/kg body weight in goats revealed that a concentration of 0.5 g/ml was maintained for 5 min-2 h, 4–12 h, 2–12 h and 5 min- >48 h in plasma, interstitial fluid, milk and urine respectively. The low t1/2 of 0.73±0.11 h and high t1/2 of 16.63±1.58 h show that the drug is rapidly distributed but slowly eliminated from the body. The tissue:plasma concentration of 4.86±1.06 during the elimination phase [K12/(K21-)] indicates a high expected tissue concentration, which is supported by similarly increased drug concentration in interstitial fluid and milk. The high Vd_area of 9.78±0.86 L/kg observed denotes that, apart from its wide distribution, the drug may be stored in fat depots as it is known to be highly lipophilic. As the drug maintained a therapeutic concentration for a shorter time in plasma, and the calculated dose rate for maintaining a minimal plasma concentration of 0.5–1.5 g/ml is relatively high, it may not be of much use in treating septicaemia in this species. Since the observed tissue:plasma concentration was higher and a therapeutic concentration was maintained in interstitial fluid and milk for longer, the drug can be used for other systemic infections at a lower dose rate than that required for treating septicaemia. As the drug maintained a very high concentration in urine, it may be of particular value in treating urinary tract infections caused by sensitive micro-organisms.     

Variation in direct and maternal genetic effects for meat production traits in Egyptian Zaraibi goats

Multi-trait analyses were carried out to quantify the (co)variation in meat production traits in Zaraibi goats. The data were obtained from a research station. There were birth weight records on 6610 kids, of which 5970 and 5237 had also pre-and postweaning gain record, respectively. The kids were progeny of 115 bucks and 1387 does, which had altogether 3603 litter size and milk yield records in different parities and which were daughters of 109 sires and 721 dams. Single-trait analyses were carried out as preliminary to a three-trait (litter size, birth weight, early growth) and five-trait (litter size, milk and growth traits) analyses. The analyses containing birth weight data required the highest number of iteration rounds in estimating the variance components using AI REML. The maternal genetic component was important for the genetic variation of birth weight and preweaning gain. In general, direct heritability was low (0.03–0.12) for growth traits, possibly due to the low-input environment. The estimates on genetic correlation between direct and maternal effects within these traits indicated mostly favourable relationship. Genetic antagonism was found between birth weight and early growth. Heritability (repeatability) for 90-day and total milk yield was 0.16–0.23 and 0.23–0.24 (0.28 and 0.39–0.40), respectively and 0.04–0.05 (0.10–0.11) for litter size. The genetic correlation between 90-day (total) milk yield and litter size was 0.45 (0.22). The correlation between the milk yield and the maternal genetic effects for the preweaning gain was very high (0.94). Selection schemes aiming to improve meat (litter size and growth) and milk production simultaneously are feasible. The increased milk production serves also for the acceleration of early growth in kids.     

Depletion of florfenicol and florfenicol amine residues in chicken eggs

1. The aim of this study was to develop a suitable method for the analysis of florfenicol (FF) and its metabolite florfenicol amine (FFA) in chicken eggs and to determine FF and FFA residue depletion in eggs of laying hens.

2. The analytes were extracted from yolk, albumen and whole egg by phosphate buffer and ethyl acetate. Following purification, samples were analysed by high-performance liquid chromatography.

3. Fifty laying hens were divided into 5 groups, and each hen received doses of 20 mg/kg FF: Group 1 (received a single oral dose by gavage); Group 2 (a single intramuscular dose); Group 3 (a single subcutaneous dose); Group 4 (multiple oral doses for 3 d) and Group 5 (multiple oral doses for 5 d).

4. Limits of detection and of quantitation values were 1.94 and 6.45 g/10⁹ g (ppb) for FF, respectively, and 0.48 and 1.58 ppb for FFA, respectively. Relative standard deviation values of intra-day and inter-day variation below 11% also confirmed the usefulness of the method for analysing FF and FFA in eggs.

5. From the first day of both oral and parenteral administration, FF and FFA were detected at 0.1% and 0.08% of dosage, respectively, and 57% of the drugs were eliminated from the egg yolk. Elimination time of FF was 8 d in Groups 1, 2 and 3; 9 d in Group 4 and 10 d in Group 5.     

Pharmacokinetic profiles of metamizole (dipyrone) active metabolites in goats and its residues in milk

Metamizole (dipyrone, MET) is a nonopioid analgesic drug commonly used in human and veterinary medicine. The aim of this study was to assess two major active metabolites of MET, 4‐methylaminoantipyrin (MAA) and 4‐aminoantipyrin (AA), in goat plasma after intravenous (IV) and intramuscular (IM) administration. In addition, metabolite concentration in milk was monitored after IM injection. Six healthy female goats received MET at a dose of 25 mg/kg by IV and IM routes in a crossover design study. The blood and milk samples were analyzed using HPLC coupled with ultraviolet detector and the plasma vs concentration curves analyzed by a noncompartmental model. In the goat, the MET rapidly converted into MAA and the mean maximum concentration was 183.97 μg/ml (at 0.08 hr) and 51.94 μg/ml (at 0.70 hr) after IV and IM administration, respectively. The area under the curve and mean residual time values were higher in the IM than the IV administered goats. The average concentration of AA was lower than MAA in both groups. Over 1 μg/ml of MAA was found in the milk (at 48 hr) after MET IM administration. In conclusion, IM is considered to be a better administration route in terms of its complete absorption with long persistence in the plasma. However, this therapeutic option should be considered in light of the likelihood of there being milk residue.     

Polymorphism of lactoferrin gene in Egyptian goats and its association with milk composition traits in Zaraibi breed

Tropical Animal Health and Production - The objectives of this study were to identify polymorphisms in the lactoferrin gene among three Egyptian goat breeds (Barki, Zaraibi, and Damascus) and to...