Renal and mammary excretion of sulfadimidine in buffaloes

The renal and mammary excretion of sulfadimidine was investigated in 8 lactating buffaloes after intravenous administration. The results showed that sulfadimidine was bound to the proteins in plasma (39--59 per cent) and milk (5.5 per cent). The renal handling of sulfadimidine was influenced by the variations in the urinary pH and the concentration of non-protein-bound drug. From the results it is concluded that glomerular filtration, back diffusion and active tubular secretion are involved in the renal handling of sulfadimidine in buffaloes. The results of mammary excretion showed that sulfadimidine is excreted into milk of buffaloes in concentration lower than in plasma. The ratio between the concentration of sulfadimidine in milk and plasma increases when the pH of milk increases. The results are consistant with the theory that drugs are excreted through the mammary gland by passive diffusion.     

Pharmacokinetics and dosage of chlorpromazine in goats

Pharmacokinetic parameters which describe the distribution and elimination of chlorpromazine in goats were determined. Following the intravenous administration of a single dose (2.5 mg/kg), disposition of the drug was described in terms of the biexponential expression C _p= Ae^-αt+ Be^-βt. Based on total (free and bound) chlorpromazine levels in plasma, pseudo-distribution equilibrium was rapidly attained, and the elimination half-life was 1.51 ± 0.48 h (mean ± SD, n = 8). Total body clearance, which is the sum of all clearance processes, was 80 ± 25 ml/min/kg. The curves of an animal representative of the group, based on individual rate constants associated with the two-compartment open model, showed that at 5 h after drug administration 8% and 6% of the dose were present in the peripheral and central compartments, respectively. The kinetic parameters of chlorpromazine determined at a dosage level of 10 mg/kg body weight in six goats showed that the drug followed first-order kinetics and kinetic parameters were similar after both dose levels. Based on these findings and therapeutic plasma levels, a satisfactory intravenous regimen should be 2.0 – 3.5 mg/kg and the drug action will persist for 5–6 h.     

Serum and milk concentrations of apramycin in lactating cows, ewes and goats

A 20% solution of apramycin was administered intravenously (j.v.) and intramuscularly (i.m.) to lactating cows with clinically normal and acutely inflamed udders, to lactating ewes with normal or subclinically infected, inflamed udders and i.v. to lactating goats with normal udders. The i.v. disposition kinetics of apramycin was very similar in cows, ewes and goats. The elimination half-life was approximately 2 h and the steady-state volume of distribution was 1.26–1.45 L/kg. The absorption rate of the drug from the i.m. injection site was rapid, the i.m. bioavailability was 60–70% and the mean elimination half-life was 265 min in cows and 145.5 min in ewes. The binding percentage of apramycin to serum protein was low (< 22.5%). Concentrations of apramycin in milk produced by clinically normal mammary glands of cows, ewes and goats were consistently lower than in serum; the kinetic value AUC _milk/ AUC _serum was < 0.32. Drug penetration into the milk from the acutely inflamed quarters of cows was extensive; mastitis milk C _max values were more than tenfold greater than the C _max in normal milk. On the other hand, the drug had limited access to the milk produced by subclinically infected inflamed half-udders of ewes.     

Pharmacokinetics and pharmacodynamics of intramammary cefquinome in lactating goats with and without experimentally induced Staphylococcus aureus mastitis

Values for pharmacokinetic variables are usually obtained in healthy animals, whereas drugs are frequently administered to diseased animals. This study investigated cefquinome pharmacokinetics in healthy goats and goats with experimentally induced mastitis. Five adult lactating goats received 75 mg of cefquinome intramammary infusion using a commercially available product into one udder half in healthy goats and goats with clinical mastitis that was induced by intracisternal infusion of 100 cfu of Staphylococcus aureus ATCC 29213 suspended in 5 ml of sterile culture broth. Cefquinome concentrations were determined in plasma and skimmed milk samples using high‐performance liquid chromatography (HPLC). Pharmacodynamics was investigated using the California Mastitis Test and pH of milk. Experimentally induced mastitis significantly increased the California Mastitis Test score and pH, and decreased the maximal cefquinome concentration and shortened the half‐life in milk when compared to healthy goats. In conclusion, mastitis facilitated the absorption of cefquinome from the mammary gland of lactating goats and induced marked changes in milk pH, emphasizing the importance of performing pharmacokinetic studies of antimicrobial agents in infected animals.     

不同精粗饲料对泌乳中期山羊氨基酸的代谢流向及乳蛋白含量的影响

 通过检测泌乳中期山羊血浆及乳中游离氨基酸含量的变化,探讨不同精粗比饲料对机体中氨基酸（ａｍｉｎｏａｃｉｄｓ,ＡＡ）的代谢流向及乳蛋白的影响。选用泌乳中期山羊７只,随机分为２组,分别饲喂精粗比４∶６（低精料组）和６∶４（高精料组）日粮,颈静脉血管瘘采血,手工挤奶取奶样。Ｂｒａｄｆｏｒｄ法测定乳中总蛋白质浓度,ＲＰ－ＨＰＬＣ检测山羊血浆和乳中游离氨基酸的含量。结果表明,２组山羊血浆中均分离出１４种游离氨基酸,乳中分离出８种游离氨基酸,不同精粗比饲料对血液或乳中游离氨基酸谱无明显影响。不同精粗比日粮情况下,除丙氨酸外,血液中游离氨基酸的含量均高于乳中同种氨基酸的含量;且血液中生酮氨基酸（Ｌｅｕ,Ｌｙｓ）、兼性氨基酸（Ｐｈｅ,Ｉｌｅ）和支链氨基酸（Ｌｅｕ,Ｉｌｅ和Ｖａｌ）含量显著或极显著高于乳中。高精料组除Ｇｌｙ和Ａｌａ外,其余氨基酸含量均低于低精料组;乳中总蛋白浓度略高于低精料组,但无统计学差异。表明血液中游离氨基酸为乳蛋白的合成提供了原料和能量保证。饲喂高精料日粮,血液中游离氨基酸含量较低,不利于乳蛋白含量和产量的提高。     

Elimination of tilmicosin in lactating ewes.

Tilmicosin was injected subcutaneously to lactating ewes once at a dose of 10 mg kg-1 b.wt. to determine its plasma, milk, urine and ruminal juice concentrations. Tilmicosin could be detected in all those fluids 30 minutes after injection. Milk and urine concentrations were higher than those of plasma and ruminal juice. The drug was detectable in milk, urine and plasma for 9, 4 and 3 days after injection, respectively. No amount of tilmicosin could be detected in ruminal juice 12 hours following administration. The mean peak concentration of tilmicosin in plasma and milk (Cmax) were 1.29 and 9.5 micrograms ml-1 and were obtained at (Tmax) 5.235 and 15.093 hours, respectively. The drug was slowly eliminated from plasma and milk as indicated by its long half-life (t1/2el) of 15.4 and 26.2 hours, respectively. The mean binding of tilmicosin to plasma and milk proteins in vitro was 16.8% and 26.8%, respectively. The drug was not bound to ruminal juice at any extent. The rate of tilmicosin renal clearance revealed that it was correspondingly increased with higher blood concentrations. While creatinine clearance showed no significant change after tilmicosin administration. The ratio (fractional clearance) between tilmicosin renal clearance to creatinine clearance was less than one indicating that the glomerular filtration is the main pathway of elimination through kidneys. The rate of ruminal gas fermentation in ewes was inhibited after subcutaneous injection of tilmicosin at a dose of 10 mg kg-1 b.wt. The tested samples taken at different time intervals from the rumen of ewes showed a subsequent reduction in the rate of fermentation as compared to control samples. The reduction was correspondingly increased with the increase of tilmicosin concentration in ruminal juice and returned to normal thereafter.     

Renal excretion of digoxin in swine and goats.

In experiments on swine and goats the renal excretion of digoxin was examined, and it was found that the renal clearance of non-protein-bound digoxin in swine was lower than creatinine clearance which expresses filtration clearance. Correlation analysis showed that the renal clearance of digoxin in swine was not significantly influenced by the concentration of non-protein-bound digoxin in plasma and the pH of the urine, while there was a significant positive correlation between the clearance and the urine flow rate (Table 4). On the other hand, the renal clearance of digoxin in goats was significantly influenced by the concentration of non-proteinbound digoxin in plasma and by urine pH (Table 4). From these results it is concluded that glomerular filtration and back-diffusion are involved in the renal handling of digoxin in both swine and goats. In addition active tubular secretion is also involved in the renal excretion of digoxin in goats.     

Pregnancy diagnosis in dairy goats and cows using progesterone assay kits

Early pregnancy diagnosis in dairy goats and cows was studied using enzyme immunoassays (EIA) to measure progesterone concentrations in whole milk samples collected approximately 3 weeks after mating. Two qualitative on-farm assay kits and 2 quantitative assay kits, all designed for use in the dairy cow, were tested for their accuracy with goats milk samples. Accuracy of diagnosis of goat pregnancy ranged from 83 to 88%, and of non-pregnancy from 80 to 100%. Pregnancy diagnosis with samples of cows milk using 2 quantitative kits gave accuracies of 66 to 68% for pregnancy, and 90 to 91% for non-pregnancy. Possible causes of error in the early diagnosis of pregnancy with milk samples are discussed.     

Permeability of the blood-milk barrier to methylene blue in cows and goats

A 2% aqueous solution of methylene blue was administered as a single intravenous (i.v.) bolus injection (10 mg/kg) to six lactating cows and seven lactating goats and as a continuous i.v. drip to five lactating goats. The same dose was administered as a 10% solution by intramammary infusion to five lactating goats. Blood and milk samples collected at various times after these treatments were assayed for the drug by a colorimetric method. Methylene blue, a highly charged molecule (pK_a<1), passed readily from blood into milk; drug concentrations in milk 4-36 h after the single i.v. bolus injection were higher than those in blood. When examined at constant methylene blue levels in blood, a milk-blood ratio of 5: 1 was observed. After intramammary infusion, the drug passed quickly into systemic circulation, peaked at 3 h and was still detectable in blood 12 h after infusion. The drug appeared in the urine within 1 5 min after intramammary infusion. The rapid movement of the drug across the blood-milk barrier cannot be explained on the basis of its known physicochemical properties or according to the pH-pK_a passive diffusion concept.     

Transfer of drugs across the ruminal wall in goats.

The rates at which pentobarbital, salicylate, antipyrine, and quinine were transferred from the rumen of intact, conscious goats were measured. The rates at which the same drugs diffused from the blood plasma (under conditions of constant drug concentration) into the ruminal solution were also evaluated. These compounds were absorbed by simple diffusion, and the rates of transfer were a function of pH of the intraruminal solution. The diffusion of drugs from plasma into the reticulorumen allowed steady-state distributions to be established in some goats. The theoretical and observed steady-state distributions were compared. There were good correlations for pentobarbital and antipyrine, but not for salicylate and quinine. These findings confirm in vivo the general principles of drug transfer across ruminal epithelium that were derived from previous studies conducted in vitro.     

Purine and pyrimidine metabolites for the estimation of rumen metabolism: HPLC analysis in milk and blood plasma

In milk and blood plasma samples of 6 German Simmental and 12 German Black and White heifers it was investigated, whether purine and pyrimidine compounds are suitable indicators of the microbial protein synthesis in the rumen. Therefore the secreted quantities in milk and the concentration in blood plasma are correlated with energy intake. The results indicated significant correlation coefficients for both the secretion quantity of allantoin in milk (r = 0.942) and the concentration of allantoin in blood plasma (r = 0.694). Other investigated compounds appeared more suitable for evaluating the mammary gland metabolism (uridine-lactose synthesis, pseudouridine-protein synthesis). In an experiment with 7 male castrated pigmy goats subjected to a four-day fasting period the decrease of plasma allantoin, which was already apparent after 12 hours of fasting, was closely correlated with the increase of plasma free fatty acids.     

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.     

Impact of lactation on pharmacokinetics of meloxicam in goats

Use of drug in lactating animal should be carefully considered due to its possibility of changes in pharmacokinetics as well as drug penetration in milk. The aim of this study was to assess the effect of lactation on pharmacokinetics of meloxicam after IV and IM administrations in goats. A crossover design (2 × 2) was used for each lactating and nonlactating group of goats with a 3-week washout period. Meloxicam (0.5 mg/kg) was administered into the jugular vein and upper gluteal muscle by IV and IM routes, respectively. The plasma and milk drug concentrations were determined by high-performance liquid chromatography with diode array detector, and the pharmacokinetic analysis was carried out by noncompartmental analysis. The pharmacokinetic parameters of meloxicam in lactating and nonlactating goats were not significantly different. The IM bioavailability of meloxicam was relatively lower in lactating (75.3 ± 18.6%) than nonlactating goats (103.8 ± 34.7%); however, the difference was not statistically significant. Moreover, AUC ratio between milk and plasma, which represent drug milk penetration, for both IV and IM administrations was less than 1 (about 0.3). In conclusion, pharmacokinetic parameters of meloxicam are not significantly altered by lactation for either the IV or IM routes of administration and this drug does not require a different dosage regimen for lactating animals.     

Use of an enzyme immunoassay to determine concentrations of progesterone in caprine plasma and milk

Concentrations of progesterone (P4) were determined using enzyme immunoassay kits on plasma and milk samples obtained on the same days from 18 lactating dairy goats. Progesterone profiles documenting anestrus, short estrous cycles, normal estrous cycles, a prolonged follicular phase, and prolonged luteal phases were established. When plasma P4 concentrations were used as an accurate indication of the presence or absence of functional luteal tissue, milk P4 concentrations agreed with plasma determinations in 79.4% of the 465 samples tested. Milk samples could not be used to make a definitive decision because of marginal values in 11.2% of the determinations. Milk P4 concentrations were high when plasma P4 concentrations were low in 6.2% of the paired samples, especially those obtained around the time of estrus when peripheral P4 concentrations were changing rapidly. The remaining 3.2% of milk samples had low milk P4 concentrations when plasma P4 concentrations were high. Composite milk from 8 does in estrus or 8 does in the luteal phase was not consistently different from strippings in butterfat percentage or P4 concentration.     

山羊奶理化性状研究——Ⅳ.末乳主要理化性状及其变化和常乳中氨基酸组成与含量

本文分析研究了西农萨能奶山羊、英国萨能奶山羊和关中奶山羊末乳中脂肪、乳糖、蛋白质、总干物质、灰分及钙和磷的含量及其变化,同时也对3个被试品种羊奶中氨基酸含量进行了测定。研究结果表明末乳中 pH 值、灰分和蛋白质含量达到整个泌乳期最高水平,而酸度和乳糖含量则较低.蛋白质含量高于脂肪含量。3个品种间氨基酸含量基本相近。山羊奶里酪蛋白中谷氨酸与组氨酸的比值明显高于牛奶.这是山羊奶酪蛋白的特点之一。山羊奶中游离氨基酸含量明显高于牛奶。     

Pharmacokinetics of danofloxacin 18% in lactating sheep and goats

The pharmacokinetics of danofloxacin administered at 6 mg/kg bodyweight by the intravenous and subcutaneous (s.c.) routes were determined in sheep and goats. Milk concentrations were also determined following s.c. administration. Plasma and milk concentrations of danofloxacin were measured using high-performance liquid chromatography. The plasma concentration-time curves were analysed by noncompartmental methods. Danofloxacin had a similar large volume of distribution at steady state in sheep and goats of 2.19 +/- 0.28 and 2.43 +/- 0.13 L/kg, and a similar body clearance of 0.79 +/- 0.15 and 0.98 +/- 0.13 L/kg.h, respectively. Following s.c. administration, danofloxacin achieved a similar maximum concentration in sheep and goats of 1.48 +/- 1.54 and 1.05 +/- 0.09 mg/L, respectively at 1.6 h and had a mean residence time of 4.93 +/- 0.79 and 4.51 +/- 0.44 h, respectively. Danofloxacin had an absolute bioavailability of 93.6 +/- 13.7% in sheep and 97.0 +/- 15.7% in goats and a mean absorption time of 2.07 +/- 0.75 and 2.01 +/- 0.53 h, respectively. Mean danofloxacin concentrations in milk after s.c. administration to sheep were approximately 10 times higher than plasma at 12 h postdose and remained eight times higher at 24 h postdose. In goats, mean concentration of danofloxacin in milk were approximately 13 times higher than plasma at 12 h postdose and remained four times higher at 24 h postdose. Thus, danofloxacin 18% administered s.c. to lactating ewes and goats at a dose rate of 6 mg/kg was characterized by extensive absorption, high systemic availability and high distribution into the udder resulting in higher drug concentrations being achieved in milk than in plasma.     

Some Pharmacokinetic Parameters of Eprinomectin in Goats following Pour-on Administration

Some pharmacokinetic parameters of eprinomectin were determined in goats following topical application at a dose rate of 0.5 mg/kg. The plasma concentration versus time data for the drug were analysed using a one-compartment model. The maximum plasma concentration of 5.60±1.01 ng/ml occurred 2.55 days after administration. The area under the concentration–time curve (AUC) was 72.31±11.15 ng day/ml and the mean residence time (MRT) was 9.42±0.43 days. Thus, the systemic availability of eprinomectin to goats was significantly lower than that for cows. The low concentration of eprinomectin in the plasma of goats suggests that the pour-on dose of 0.5 mg/kg would be less effective in this species than in cows. Further relevant information about the optimal dosage and residues in the milk of dairy goats is needed before eprinomectin should be used in this species.     

Comparative pharmacokinetics of diminazene in lactating goats and sheep

The pharmacokinetic aspects of diminazene aceturate were studied in lactating goats and sheep after single intravenous and intramuscular administrations of 3.5 mg/kg b.wt. Plasma and milk concentrations were determined by use of reversed phase high-performance liquid chromatography (HPLC) after ion-pair extraction. Following intravenous injection, the disposition of diminazene in goats and sheep conformed to a two-compartment model with rapid distribution and slower elimination phases. Values of (t1/2 beta) were obtained indicating a slower final disappearance of the drug from plasma of sheep (21.17 h) than in goats (16.39 h). Diminazene concentrations were maintained for more than 4 days in the plasma of goats and sheep. In both species of animals, diminazene was rapidly absorbed following intramuscular administration of 3.5 mg/kg b.wt. The peak plasma concentrations (Cmax) were 7.00 and 8.11 micrograms/ml and were attained at (Tmax) 0.92 and 1.12 hours in goats and sheep, respectively. The elimination half-life (t1/2el) of diminazene after intramuscular administration was shorter in goats (16.54 h) than in sheep (18.80 h). Systemic bioavailabilities (F%) of diminazene after intramuscular administration were 94.94% and 82.64% in goats and sheep, respectively. Diminazene could be detected in milk of goats and sheep within 10 min post-injection. Milk concentrations of the drug were lower in goats than in sheep and were detected for 5 and 6 days following both routes of administration, respectively.     

Growth hormone-binding protein in the goat: characterization, evolution under exogenous growth hormone treatment, and correlation with liver growth hormone receptor levels

This report describes the identification and characterization of a specific, high-affinity growth hormone-binding protein (GHBP) in lactating goat serum. Serum samples were incubated with [¹²⁵I]human GH as ligand and in the absence or in the presence of bovine GH as competitor. GH-GHBP complex formation was performed by high-performance liquid chromatography, and the radioactivity was recorded on-line with a Berthold LB detector connected to a computer. The results showed that a serum protein was able to bind specifically to human GH and bovine GH but not to ovine prolactin. Scatchard plots indicated an affinity constant of 4.5 × 10⁸ M⁻¹ and a maximum binding capacity of 4.8 × 10⁻¹⁰ mol/l. In addition, we conducted a 4-wk study to determine the effects of recombinant bovine GH administration on milk production in lactating goats. The effects of recombinant bovine GH treatment on milk production and on the regulation of GHBP and hepatic GH receptor levels were studied. As expected, recombinant bovine GH injected daily increased yields of milk, fat, protein (40, 61, and 40%, respectively), and circulating insulin-like growth factor 1 concentrations compared with controls. During the pretreatment and treatment periods, the control goats exhibited a constant amount of GHBP in serum. No consistent effect of GH treatment on GHBP level was observed. The binding of [¹²⁵I]bovine GH to hepatic microsomal membranes of GH-treated goats was significantly decreased compared with that of control goats. After MgCl₂ desaturation of membranes, the results demonstrated that the down-regulation of GH hepatic receptors, observed for the treated goat group, was induced by receptor occupancy without modification of binding affinity. The GH receptor gene expression, analyzed by slot blot and hybridization with an [-³²P]GH receptor cDNA probe, was not modified by the GH treatment. In lactating goats, the galactopoietic effect of exogenous GH involved a hepatic receptor occupancy. The individual concentration of GHBP in serum cannot explain the individual variations of responses to GH treatment in goats.     

Isometamidium in goats: disposition kinetics, mammary excretion and tissue residues

The pharmacokinetics of the antitrypanosomal drug isometamidium were studied in lactating goats after intravenous and intramuscular administration at a dose of 0.5 mg/kg body weight, in a crossover design at an interval of 6 weeks. Following intravenous administration, the half-life of the disappearance of the drug from plasma during the terminal phase was 3.2 h, and the mean residence time was 2.4 h. The apparent volume of distribution averaged 1.52 l/kg, and the mean total body clearance was 0.308 l/kg/h. After intramuscular administration, the absolute bioavailability was low, averaging 27%. This was consistent with a low mean maximum concentration of 24 ng/ml which occurred after 6 h. No drug was detectable (less than 10 ng/ml) in milk samples collected over a period of 14 days following drug administration by either the intravenous or intramuscular route. In tissues analysed when the goats were killed 6 weeks after administration of the second dose, no drug was detectable (less than 0.4 micrograms/g wet tissue) in the liver, kidney and muscle. However, at the injection site, drug concentrations varied from less than 0.4 to 18.8 micrograms/g wet tissue.