ELISA detection of fentanyl in horse urine and plasma

The prototype of a commercial ELISA test kit designed for fentanyl determination in human urine has been evaluated for screening fentanyl in horse urine and plasma. The measurement of fentanyl after intravenous (2 mg) and intramuscular (0.25 mg) administration in undiluted plasma was not reproducible while accurate quantification of fentanyl in urine greatly depends on the composition of the horse urine. The ELISA assay, however, is simple and could be successfully used for quantitative measurements in diluted urine and for rapid qualitative screening for fentanyl in large numbers of urine samples.     

Presence and content of kynurenic acid in animal feed

Kynurenic acid (KYNA) was found to be an antagonist of iontropic glutamate receptors and alpha7 nicotinic acetylcholine receptors. Furthermore, it was documented that KYNA is an agonist of G‐protein coupled GPR35 receptors which are mainly present in the gastrointestinal tract. It was also found that KYNA is present in the gastrointestinal tract and that its concentration gradually increases along it. The origin of KYNA in the gastrointestinal tract is not known. Both might be synthesized from tryptophan in it or absorbed from food and other dietary products. Therefore, the aim of the study was to investigate the concentration of KYNA in animal feed. The results indicate that the highest concentration of KYNA was found in animal feeds intended for livestock. The lower amount of KYNA was detected in animal feeds for fish. Interestingly, the lowest amount of KYNA was found in dog and cat feeds. Furthermore, an analysis of KYNA content in animal food ingredients was conducted. The concentration of KYNA found in one of the ingredients – rapeseed meal – was several times higher in comparison to animal feeds studied. The content of KYNA in the remaining feed ingredients tested was significantly lower. This is the first report on the concentration of KYNA in animal feeds. There is a need for further detailed analysis leading to establishing a set of guidelines for animal feeding.     

Pharmacokinetic/pharmacodynamic approach to assess irrelevant plasma or urine drug concentrations in postcompetition samples for drug control in the horse

The current performance of analytical techniques used for drug control in horses lead the Regulatory Authorities to decide whether trace levels of drugs legitimately used for therapeutic medication should or should not be reported. Here, we propose a well-ordered and nonexperimental pharmacokinetic/pharmacodynamic approach for the determination of irrelevant drug plasma (IPC) and urine concentrations (IUC). The published plasma clearance is used to transform an effective (marketed) dose into an effective concentration (EPC). EPC is transformed into an IPC by applying a safety factor (SF). This method is based on several assumptions (eg, drug effects reversibly driven by plasma concentration, linearity of drug disposition). The suitability of the computed IPC and IUC can be checked by calculating the residual amount of drug at IPC and computing a minimal drug withdrawal time. It is concluded that controlling the drug effect (using drug or any analyte concentration as a marker) rather than the drug exposure will be more demanding and also makes urine a less than ideal matrix.     

Interstitial lung fibrosis and emphysema in a standardbred horse: A case report

A horse with severe work-intolerance was examined. Neither clinical nor radiographic examination suggested the presence of emphysema and lung fibrosis.     

Pharmacokinetics of norfloxacin in dogs after single intravenous and single and multiple oral administrations of the drug

Norfloxacin was given to 6 healthy dogs at a dosage of 5 mg/kg of body weight IV and orally in a complete crossover study, and orally at dosages of 5, 10, and 20 mg/kg to 6 healthy dogs in a 3-way crossover study. For 24 hours, serum concentration was monitored serially after each administration. Another 6 dogs were given 5 mg of norfloxacin/kg orally every 12 hours for 14 days, and serum concentration was determined serially for 12 hours after the first and last administration of the drug. Complete blood count and serum biochemical analysis were performed before and after 14 days of oral norfloxacin administration, and clinical signs of drug toxicosis were monitored twice daily during norfloxacin administration. Urine concentration of norfloxacin was determined periodically during serum acquisition periods. Norfloxacin concentration was determined, using high-performance liquid chromatography with a limit of detection of 25 ng of norfloxacin/ml of serum or urine. Serum norfloxacin pharmacokinetic values after single IV dosing in dogs were best modeled, using a 2-compartment open model, with distribution and elimination half-lives of 0.467 and 3.56 hours (harmonic means), respectively. Area-derived volume of distribution (Vd area) was 1.77 +/- 0.69 L/kg (arithmetic mean +/- SD), and serum clearance (Cls) was 0.332 +/- 0.115 L/h/kg. Mean residence time was 4.32 +/- 0.98 hour. Comparison of the area under the curve (AUC; derived, using model-independent calculations) after iv administration (5 mg/kg) with AUC after oral administration (5 mg/kg) in the same dogs indicated bioavailability of 35.0 +/- 46.1%, with a mean residence time after oral administration of 5.71 +/-2.24 hours. Urine concentration was 33.8 +/- 15.3 micrograms/ml at 4 hours after a single dose of 5 mg/kg given orally, whereas concentration after 20 mg/kg was given orally was 56.8 +/- 18.0 micrograms/ml at 6 hours after dosing. Twelve hours after drug administration, urine concentration was 47.4 +/- 20.6 micrograms/ml after the 5-mg/kg dose and 80.6 +/- 37.7 micrograms/ml after the 20/mg/kg dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rifampin in the horse: comparison of intravenous, intramuscular, and oral administrations

The plasma concentrations and pharmacokinetics of rifampin disposition were determined after a single IV, IM, or oral dose of 10 mg/kg of body weight and an oral dose of 25 mg/kg. The overall elimination rate constants per minute were similar for the 10 mg/kg dose (0.0021 +/- 0.0004, IV; 0.0017 +/- 0.0002, IM; and 0.0023 +/- 0.0006, orally). The apparent bioavailability was moderate to low for IM and oral administrations (59.8% +/- 3.2% and 39.5% +/- 5.0%, respectively). The rate of absorption was most rapid for oral administration with an absorption half-life of 249.7 +/- 71.6 minutes as compared with 403.5 +/- 89.7 minutes for IM administration. However, the IM route produced longer detectable plasma concentrations (50 hours in 2 of the 4 horses). Based on bacterial sensitivity information derived for human and canine isolates, the daily oral administration of 10 mg of rifampin/kg administered in the feed represents a reasonable dose for susceptible gram-positive bacterial pathogens. Higher doses (greater than or equal to 25 mg/kg) or IV administration would be required for most gram-negative bacteria. Adverse effects of sufficient severity to limit use of the drug, especially by the oral route of administration, were not encountered under the single-dose experimental conditions used.     

马的营养需要和饲料消耗

表1马的预期饲料消耗t(以马体孟的%计)’饲草精饲料总计成年马维持母马,妊娠后期母马,妊娠早期母马,泌乳后期役用马轻量级中量级重量级幼马哺乳马驹(3月龄)断奶马驹(6月龄)1岁幼马1岁半幼马2岁马1风干饲料(约90%干物质)。1 .5~2.01 .0~1.51 .0~2.01 .0~2.0 O一0.50 .5一1 .01 .0一2.00 .5一1 .51 .5一2.01 .5一2.02 .0一3.02 .0一2.5 1 .0~2.0 1 .0~2.0075~1.505一1 .00 .75一151 .0一2.0 1 .5一2.51 .75一2.52.0一2.5 00,5一1 .01 .0一1.51 .0一1.51 .0~1.510一201 .5一3.01 .0一2.01 .0一151 .0一1.52 .5一3.52 .0~3.52刀一3.020一2 .52 …     

Analysis of propionylpromazine and its metabolites in horse urine

The metabolism of propionylpromazine in the horse was studied. Although propionylpromazine is not currently approved or recommended for use in horses, it has been used illegally to alter their performance. Propionylpromazine hydrochloride was administered intramuscularly at clinical and subclinical doses. Three metabolites were detected in urine. The major metabolite was identified as 2-(1-hydroxypropyl) promazine sulfoxide. The detection of this metabolite in routine drug testing has been described.     

Somatotropin and insulin-like growth factor-I concentrations in plasma and milk after daily or sustained-release exogenous somatotropin administrations

Effects of daily injectable or sustained-release bovine somatotropin (bST) administrations on plasma and milk bST and insulin-like growth factor-I (IGF-I) concentrations were monitored in 74 lactating cows through early, mid- and late lactation. Treatments beginning at wk 4 of lactation were excipient (CO, 24 cows) at 2 wk intervals, daily injections of 10.3 mg bST (DI, 25 cows) and 350 mg sustained-release bST at 2 wk intervals (SR, 25 cows). The duration of treatments was 40 wk. Data were first analyzed for the overall mean concentrations covering the 40 wk treatment period. Overall mean plasma bST, milk bST and plasma IGF-I concentrations were significantly increased by both bST treatments (p<0.05). On the other hand, milk IGF-I concentrations were significantly increased (p<0.05) only in the DI group. Next, data were analyzed according to stage of lactation. The bST treatments resulted in significant increases (p<0.05) in plasma and milk bST concentrations for all early, mid- and late lactation periods. Even though plasma IGF-I concentrations were higher (p<0.05) in all lactation periods for bST treatment groups, higher milk IGF-I concentrations (p<0.05) occurred only in mid- and late lactation periods for the DI group. The patterns of bST and IGF-I concentrations in milk follows those of the plasma after bST treatments.     

Synovial fluid and plasma concentrations of ceftiofur after regional intravenous perfusion in the horse

OBJECTIVE: To determine radiocarpal (RC) joint synovial fluid and plasma ceftiofur concentrations after regional intravenous perfusion (RIP) and systemic intravenous (IV) administration. STUDY DESIGN: Experimental cross-over study. ANIMALS: Five normal adult horses. METHODS: One RC joint was randomly selected for RIP and the contralateral RC joint was sampled to determine intrasynovial ceftiofur concentrations after IV administration. Wash-out between IV and RIP was > or = 14 days. After surgical introduction of an intraarticular catheter, ceftiofur (2 g) was administered under general anesthesia either IV or by RIP after tourniquet application. Plasma and synovial fluid were collected over 24 hours. Samples were analyzed using high-performance liquid chromatography with ultraviolet detection and the results were statistically analyzed using a linear mixed effect model. RESULTS: Mean synovial fluid ceftiofur concentrations were consistently higher after RIP than after IV administration and were > 1 mug/mL (minimal inhibitory concentration [MIC] for common pathogens) for >24 hours. Mean synovial fluid peak concentration of ceftiofur after RIP and IV administration was 392.7+/-103.29 microg/mL at 0.5 hours postinjection (HPI) and 2.72+/-0.31 mug/mL at 1 HPI, respectively. Large variations in synovial fluid and plasma ceftiofur concentrations were observed between horses regardless of administration technique. RIP did not cause adverse effects. CONCLUSIONS: Under the present experimental conditions RIP with ceftiofur (2 g) induced significantly higher intraarticular antibiotic concentrations in the RC joint in comparison with IV administration. Moreover, after RIP, synovial fluid ceftiofur concentrations remain above the MIC for common pathogens (1 microg/mL) for > 24 hours. No adverse effects from the technique or the antibiotic were observed. CLINICAL RELEVANCE: RIP with high doses of ceftiofur may be a beneficial adjunctive therapy when treating equine synovial infections which are caused by cephalosporin susceptible microorganisms.     

Elimination of salicylic acid in goats and cattle

Sodium salicylate was administered to cattle and goats IV and PO according to a crossover design. Total urinary excretion of SA and its metabolites was measured for 3 days after dosing. Salicyluric acid (SUA) was the only metabolite detected in urine of either species. Recovery of sodium salicylate and SUA in goats amounted to 67.9 and 34.6% of the dose, respectively, after IV administration. After oral dosing, total recoveries were 30.2% (sodium salicylate) and 71.7% (SUA) of dose. By comparison, cattle excreted significantly (P less than 0.05) less sodium salicylate (54.0%) and more SUA (49.9%) after IV dosing. The same pattern was observed after oral administration, wherein cattle excreted less than 12% as sodium salicylate and more than 99% as SUA. In both species, almost 90% of the drug excreted as sodium salicylate was found in urine within the first 12 hours after an IV dose and within 24 hours after oral dosing. The excretion of SUA was somewhat slower in both species, especially after oral administration. The data suggested that there were only quantitative differences in the metabolism and elimination of sodium salicylate between the 2 species, with cattle excreting a higher proportion of the drug as the glycine conjugate SUA.     

Pharmacokinetics and elimination of salicylic acid in rabbits

Sodium salicylate was administered to rabbits in order to compare its disposition with that in other major and minor agricultural species. A dose of 44 mg/kg was given orally (p.o.) or intravenously (i.v.), and plasma and urine samples were collected for 36 h and 96 h, respectively. The majority of the drug was excreted as salicylic acid (SA) within 12 h. The major metabolites following an oral dose were salicyluric acid (SUA) and the glucuronide conjugates of SA and SUA. Following i.v. dosing, sulfate conjugates of both SA and SUA were also evident. Both SA and SUA were detected in plasma. Following i.v. administration, SA was distributed with a Vss of 0.249 +/- 0.082 l/kg and cleared at a rate of 0.0432 +/- 0.006 l/h/kg. The biological half-life, calculated from the terminal disposition-rate constant, was 4.3 h (i.v.) or 9.7 h (p.o.). The urinary elimination pattern of SA and metabolites in the rabbit was similar to that previously reported by our laboratories for cattle and goats, although total recovery of the administered dose was not as high as for the latter two species. However, the volume of distribution was larger than for cattle and goats, and rabbits cleared the drug more slowly than those species. As a consequence, the biological half-life was eight to ten times longer than in the ruminants studied previously.     

3种不同柑橘品种水杨酸处理前后对溃疡病的抗性分析

为了探明对溃疡病敏感度存在差异的金柑、甜橙和枳在水杨酸处理前后的抗病性差异,对3种柑橘材料进行外源水杨酸处理并进行溃疡病菌接种。结果表明,3种柑橘材料中,金柑对溃疡病抗性最高,其次为甜橙。枳对溃疡病的抗性最低,病害症状最显著且细菌增殖最快;经过水杨酸处理后3种柑橘材料对溃疡病的抗性都有不同程度的提高,死亡细胞数量减少、相对电导率含量降低、细菌数量也显著减少。进一步分析3种不同柑橘材料水杨酸处理中抗病基因的表达模式发现,金柑中NPR1、PAD4、PR1基因被显著诱导上调表达,且高于其余两种柑橘材料,表明金柑对溃疡病的高抗能力可能与其体内显著上调的抗病基因相关。     

Principles of drug disposition in the horse

This article is intended to give the reader an understanding of the mathematic and conceptual framework underlying equine pharmacology. The methods by which the veterinary practitioner determines drug concentrations, disposition, and bioavailability are discussed.