Pharmacokinetics and Dosage Regimen of Ceftriaxone in Buffalo Calves

The pharmacokinetics and dosage regimen of ceftriaxone were investigated in buffalo calves (n = 6) following a single intravenous administration of ceftriaxone (10 mg/kg). The elimination rate constant was 0.18 +/- 0.01 h(-1) and the elimination half-life was 3.79 +/- 0.09 h. The apparent volume of distribution (Vd(area)) was 1.40 +/- 0.01 L/kg and the total plasma clearance was 0.26 +/- 0.01 L/(kg h). Approximately 43% of total administered dose of ceftriaxone was excreted in urine within 8 h. To maintain a minimum therapeutic concentration of 1 microg/ml, a satisfactory intravenous dosage regimen of ceftriaxone in buffalo calves is 13 mg/kg repeated at 12 h intervals.     

The Disposition Kinetics,Urinary Excretion and Dosage Regimen of Ciprofloxacin in Buffalo Calves (Bubalus bubalis)

The disposition kinetics, urinary excretion and a dosage regimen for ciprofloxacin after a single intravenous administration of 5 mg/kg was investigated in 5 healthy buffalo calves. The disposition kinetics were best fitted to a three-compartment open model. After 1 min, the concentration of ciprofloxacin in plasma was 8.50±0.39 g/ml and the minimum therapeutic concentration was maintained for 10 h. The elimination half-life and volume of distribution were 3.88 and 0.08 h and 3.97±0.22 L/kg, respectively. The total body clearance and T/P ratio were 0.709±0.025 L/kg per h and 6.13±0.54, respectively. Approximately 28.3% of the total administered dose of ciprofloxacin was recovered in urine within 24 h of administration. To maintain a minimum therapeutic plasma concentration of 0.10 g/ml, a satisfactory intravenous dosage regimen of ciprofloxacin, computed on the basis of disposition kinetic data obtained in healthy buffalo calves, would be 3 mg/kg repeated at 12 h intervals.     

Plasma Concentrations,Pharmacokinetics and Urinary Excretion of Gatifloxacin after Single Intravenous Injection in Buffalo Calves

The pharmacokinetics and urinary excretion of gatifloxacin were investigated after a single intravenous injection of 4 mg/kg body weight in buffalo calves. The therapeutic plasma drug concentration was maintained for up to 12 h. Gatifloxacin rapidly distributed from blood to tissue compartments, which was evident from the high values of the distribution rate constant, α₁ (11.1 ± 1.06 h⁻¹) and the rate constant of transfer of drug from central to peripheral compartment, k ₁₂ (6.29 ± 0.46 h⁻¹). The area under the plasma drug concentration–time curve and apparent volume of distribution were 17.1 ± 0.63 (μg.h)/ml and 3.56 ± 0.95 L/kg, respectively. The elimination half-life (t _{1/2 β}), total body clearance (Cl_B) and the ratio of drug present in tissues and plasma (T/P) were 10.4 ± 2.47 h, 235.1 ± 8.47 ml/(kg.h) and 10.1 ± 2.25, respectively. About 19.7% of the administered drug was excreted in urine within 24 h. A satisfactory intravenous dosage regimen for gatifloxacin in buffalo calves would be 5.3 mg/kg at 24 h intervals. Abbreviations for pharmacokinetic parameters are given in the footnote of Table I     

Pharmacokinetics and Dosage Regimen of Enrofloxacin in Buffalo Bulls after Intramuscular Administration

The disposition kinetics and dosage regimen of enrofloxacin were investigated in breeding buffalo bulls following a single intramuscular administration of 5 mg/kg. The absorption half-life, half-life of the terminal phase, apparent volume of distribution and total body clearance were 0.262±0.099 h, 1.97±0.23 h, 0.61±0.13 L/kg and 210.2±18.6 ml/(kg.h), respectively. Therapeutic plasma levels (1 g/ml) were maintained for up to 6 h. A satisfactory intramuscular dosage regimen for enrofloxacin in buffalo bulls would be 8.5 mg/kg followed by 8.0 mg/kg at 8 h intervals.     

Intramuscular Kinetics and Dosage Regimens for Pralidoxime in Buffalo Calves (Bubalus bubalis)

The plasma levels, disposition kinetics and a dosage regimen for pralidoxime (2-PAM) were investigated in male buffalo calves following single intramuscular administration (15 or 30 mg/kg). The effects of 2-PAM on various blood enzymes were also determined. The absorption half-life, elimination half-life, apparent volume of distribution and total body clearance of 2-PAM were 1.08±0.19 h, 3.14–3.19 h, 0.83–1.01 L/kg and 184.9–252.1 ml/(kg h), respectively. At doses of 15 and 30 mg/kg body weight, a plasma concentration 4 g/ml was maintained for up to 4 and 6 h, respectively. Pralidoxime significantly lowered the serum level of transferases, phosphatases and lactate dehydrogenase but did not influence the acetylcholinesterase and carboxylesterase enzymes. The most appropriate dosage regimen for 2-PAM in the treatment of organophosphate toxicity in buffaloes would be 25 mg/kg followed by 22 mg/kg at 8 h intervals.     

Some Comparative Aspects of the Pharmacokinetics of Tylosin in Buffaloes and Cattle

The pharmacokinetics of tylosin were compared in cattle (Bos taurus) and buffaloes (Bubalus bubalis). Six animals received each a single dose of 10 mg/kg of tylosin tartrate by the intramuscular route. The serum concentration (C _max) and the volume of distribution (V _d) presented significant differences between the two species. C _max was 0.40 ± 0.046 µg/ml for buffaloes and 0.64 ± 0.068 µg/ml for cattle. V _d was 1.91 ± 0.12 L/kg and 1.33 ± 0.09 L/kg for buffaloes and cattle, respectively. However, as the present study did not show considerable differences in the pharmacokinetics of tylosin in buffaloes and cattle, similar dosage regimes of this drug can be recommended for both species.     

Some Pharmacokinetic Parameters and Dosage Regimens for a Long-Acting Formulation of Oxytetracycline in 6- to 8-Month-Old Male Calves

A two-way crossover study was conducted in crossbred male calves (6–8 months old) to determine the bioavailability, pharmacokinetics and dosage regimens for a long-acting formulation of oxytetracycline (OTC-LA). The half-lives of oxytetracycline after intravenous and intramuscular administration were 7.8 h and 24 h, respectively. The volume of distribution and total body clearance values of the drug were 0.86±0.07 L and 76.1±3.3 (ml/h)/kg, respectively. The maximum concentration of the drug in the serum (4.7–7.4 g/ml) was achieved 8–10 h after intramuscular administration. The minimum therapeutic serum concentration of drug of 0.5 g/ml was maintained between 15 min and 84 h after intramuscular administration. The intramuscular bioavailability of the drug was 89.1±4.2%. The dosage regimens to maintain the minimum therapeutic serum concentrations of OTC following intramuscular administration of OTC-LA were computed.     

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.     

Pharmacokinetics of Enrofloxacin and Its Metabolite Ciprofloxacin after Intramuscular Administration of Enrofloxacin in Goats

The pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were investigated in goats after a single intramuscular administration of enrofloxacin at 2.5 mg/kg body weight. The plasma concentrations of enrofloxacin and ciprofloxacin were determined simultaneously by a HPLC method. The peak concentrations (C _max) of enrofloxacin (1.13 g/ml) and ciprofloxacin (0.24 g/ml) were observed at 0.8 and 1.2 h, respectively. The elimination half-life (t _1/2), volume of distribution (V _d(area)), total body clearance (Cl_B) and mean residence time (MRT) of enrofloxacin were 0.74 h, 1.42 L/kg, 1329 ml/h per kg and 1.54 h, respectively. The t _1/2, area under the plasma concentration–time curve (AUC) and the MRT of ciprofloxacin were 1.38 h, 0.74 g h/ml and 2.73 h, respectively. The metabolic conversion of enrofloxacin to ciprofloxacin was appreciable (36%) and the sum of the plasma concentrations of enrofloxacin and ciprofloxacin was maintained at or above 0.1 g/ml for up to 4 h. Enrofloxacin appears to be useful for the treatment of goat diseases associated with pathogens sensitive to this drug.     

Disposition kinetics and urinary excretion of cefpirome after intravenous injection in buffalo calves

We investigated the disposition kinetics and urinary excretion of cefpirome in buffalo calves after a single intravenous administration of 10 mg/kg. Also, an appropriate dosage regimen was calculated. At 1 min after injection, the concentration of cefpirome in the plasma was 57.4 ± 0.72 µg/ml, which declined to 0.22 ± 0.01 µg/ml at 24 h. The cefpirome was rapidly distributed from the blood to the tissue compartment as shown by the high distribution coefficient values (8.67 ± 0.46/h), and by the drug''s rate of transfer constant from the central to the peripheral compartment, K₁₂ (4.94 ± 0.31/h). The elimination halflife and the volume of distribution were 2.14 ± 0.02 h and 0.42 ± 0.005 l/kg, respectively. Once the distribution equilibrium was reached between the tissues and plasma, the total body clearance (Cl_B) and the ratio of the drug present in the peripheral to the central compartment (T/P ratio) were 0.14 ± 0.002 l/kg/h and 1.73 ± 0.06, respectively. Based on the pharmacokinetic parameters we obtained, an appropriate intravenous cefpirome dosage regimen for treating cefpiromesensitive bacteria in buffalo calves would be 8.0 mg/kg repeated at 12 h intervals for 5 days, or until persistence of the bacterial infection occurred.     

Disposition Kinetics,Bioavailability and Renal Clearance of Cefepime in Calves

The pharmacokinetics of cefepime were studied following intravenous and intramuscular administration of 6.5 mg/kg in four female Friesian calves. Following single intravenous administration, the serum concentration-time curves of cefepime were best fitted using a two-compartment open model. The elimination half-life (t(1/2)beta) was 2.38+/-0.16 h, volume of distribution at steady state (Vdss) was 0.21 +/- 0.01 L/kg, and total body clearance (ClB) was 1.1 +/- 0.08 ml/min per kg. Following intramuscular administration, the drug was rapidly absorbed with an absorption half-life (t(1/2)ab) of 0.29+/-0.02 h; maximum serum concentration (Cmax) of 21.7 +/- 1.1 microg/ml was attained after (Tmax) 1.1 +/- 0.08 h; and the drug was eliminated with an elimination half-life (t(1/2)el) of 3.02 +/- 0.18 h. The systemic bioavailability (F) after intramuscular administration of cefepime in calves was 95.7% +/- 7.44%. The in vitro serum protein-binding tendency was 10.5-16.7%. Following administration by both routes, the drug was excreted in high concentrations in urine for 24 h post administration.     

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.     

Effect of Weaning Stress on Blood Physiology and Biochemistry Indexes and Immune Function in Dairy Buffalo Calves

To study the effect of weaning stress on dairy buffalo calves,5 healthy calves were chosen and weaned,and the blood samples were collected at 1 day before weaning,and 1,14 and 21 days after weaning to analysis blood physiology and biochemistry indexes and immune function.The results showed that the count of white blood cell,lymphocyte,erythrocyte,monocytes and hematocrit,aspartate aminotransferase activity,blood glucose,cortisol and immunoglobulin G contents of dairy buffalo calves were no significant difference between before and after weaning treatments (P > 0.05).The count of neutrophils at 21 d after weaning were significantly lower than that of 1 d before weaning of dairy buffalo calves (P < 0.05).However,lactate dehydrogenase and alanine aminotransferase activity in weaned treatments were significantly higher than those of animals in the treatment before weaning (P < 0.05).The serum urea nitrogen of dairy buffalo calves at 21 d after weaning was significantly higher than that of 1 d before weaning (P < 0.05) and hemoglobin content at 21 d after weaning was significantly lower than that at 1 day before weaning (P < 0.05).It indicated that the physiological and immunity function of dairy buffalo calves were challenged under weaning stress.     

不同补饲水平摩本杂F_1代奶水牛犊牛增重效果研究

[目的]本试验旨在提高犊牛早期日增重的方法,进行本次试验。[方法]采用日龄、体型、体重均相近的1月龄以内的摩本杂F1代奶水牛犊牛14头,随机分成试验A组和试验B组,分别饲喂不同日粮(试验A组完全补饲精料补充料、试验B组补饲精料补充料与苜蓿颗粒各占50%),试验期为163d,试验结束后比较两组的日增重。[结果]补饲水平不同对云南摩本杂F1代奶水牛犊牛早期增重影响很大,试验A组增重效果明显好于试验B组。[结论]试验表明在云南摩本杂F1代奶水牛犊牛早期饲养过程中适当增加精料补充料的饲喂量,可以获得更高日增重。     

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.     

复方磺胺间甲氧嘧啶(CO.SMM)缓释型注射液在水牛体内的血浆药动学

为研究复方磺胺间甲氧嘧啶（CO．SMM）缓释型注射液的药代动力学规律，选择健康水牛8头，随机分成2组（n=4），对照组和试验组分别按50mg／kg剂量肌注单方SMM和CO．SMM缓释型注射液，采用高效液相色谱法测定血浆药物浓度。利用药代动力学程序软件3P97处理药时数据，计算药代动力学参数。结果显示：（1）肌注单方SMM注射液后药时数据符合一级吸收二室开放模型，t1/2Ka 0．47h，t1／2 β 3．25h，AUC261．19h·μg·mL^-1，Vd0．89L／kg，CLB0．19L·kg^-1·h，tmax 1．02h，Cmax76．85mg／L。（2）肌注CO．SMM缓释型注射液后，SMM药时数据符合一级吸收一室开放模型，t1／2Ka 0．41h，t1/2β 11．46h，AUC 1107h·μg·mL，Vd0．75L·kg^-1，CLB0．05L·kg^-1·h^-1，tmax 2．03h，Cmax 59．24μg·mL；肌注CO．SMM缓释型注射液后，TMP药时数据符合一级吸收二室开放模型，t1／2Ka 0．87h，t1／2β19．59h，AUC83．66h·μg·mL^-1，Vd16．89L·kg^-1，CLB0．60L·kg^-1·h^-1，tmax2．95h，Cmax 4．15μg·mL^-1。结果表明，CO．SMM缓释型注射液肌注水牛后SMM在体内消除缓慢，达峰时间延迟，血药浓度平稳，具有缓释、增效的作用。     

血清对水牛卵母细胞体外成熟、体外受精及早期胚胎发育的影响

从屠宰场收集了本地水牛55头、黑白花奶牛22头的卵巢共获卵泡847枚,平均每个水牛卵巢回收3.67枚可用卵母细胞,约为黑白花奶牛(10.23枚/头)的1/3。试验分别采用添加与不添加血清的培养液体外成熟培养水牛卵母细胞,结果二者的成熟率无明显毒性差异(58.23%对56.67%),但体外受精后早期胚胎发育的8-细胞率有显著差异(35.4%对23.0%),表明体外成熟液中有无血清对水牛卵母细胞体外成熟率没有影响,但血清对卵母细胞的早期胚胎发育有重要影响。进一步比较成熟液中不添加血清但在受精液及胚胎液中添加血清和在各个阶段均有血清参与的早期胚胎发育率(8-细胞率),表明二者差异不显著(33.8%对35.4%)。经无血清成熟培养液培养的成熟卵母细胞可以经孤雌激活后得到早期胚胎(4细胞)。     

Cloning of Buffalo AQP9 Gene and Analysing its Expression in the Buffalo Tissues

Cloning buffalo AQP9 gene and analyzing its expression in buffalo tissues.A pair of primers was designed according to the released bovine AQP9 sequences in GenBank,which was used to clone buffalo AQP9 gene.The AQP9 gene was amplified by RT-PCR,whose nucleotide sequence and protein structure were analyzed by bioinformatics methods.The expression of AQP9 in buffalo tissues was assayed by Real-time quantitative PCR.The expression of AQP9 gene in buffalo ovary and testis tissue was detected by immunohistochemical staining method.The results showed that the cloned ORF length of buffalo AQP9 gene was 888 bp,which coded 295 amino acids.The results of multiple sequence comparison showed that the nucleotide sequence of buffalo AQP9 shared 99%,90%,97% and 88% homologeous compared with that of Bos taurus,Sus scrofa,Ovis ariessis and Homo sapiens,respectively,while shared 99%,86%,97%,83% homologeous for amino acids,respectively.Phylogenetic tree analysis indicated that AQP9 gene was highly conservative in the evolutionary process.Real-time quantitative PCR results showed that AQP9 gene expressed in buffalo liver,lung,brain,skin,testis and ovary tissues with different levels,had the most abundant expression in liver,followed by in skin and testis,less observed in lung and ovary.The results of immunohistochemical staining showed that the expression of AQP9 protein varied with the development of buffalo ovarian tissue,and gradually enhanced with follicle development.In testicular tissue,AQP9 protein expressed in spermatocyte and leydig cells of developmental stage testis.These results indicated that we had successfully cloned buffalo AQP9 gene sequences.The expression and its function of AQP9 in buffalo ovaries and testes might play an important role in follicle development and spermatogenesis.