Disposition and oral bioavailability of amoxicillin and clavulanic acid in pigs

The pharmacokinetic properties of amoxicillin and clavulanic acid were studied in healthy, fasted pigs after single intravenous (i.v.) and oral (p.o.) dosage of 20 mg/kg of amoxicillin and 5 mg/kg of clavulanic acid. The plasma concentrations of the drugs were determined by validated high-performance liquid chromatographic methods and the pharmacokinetic parameters were calculated by compartmental and noncompartmental analyses. After i.v. administration of the two drugs, plasma concentration-time curves were best described by a three-compartmental open model for amoxicillin and a two-compartmental open model for clavulanic acid. Amoxicillin (with a t(1/2 gamma) = 1.03 h and a clearance of 0.58 L/h.kg) and clavulanic acid (with a t(1/2 beta) of 0.74 h and a clearance of 0.41 L/h.kg) were both rapidly eliminated from plasma. Both drugs had apparently the same volume of distribution of 0.34 L/kg. After p.o. administration of the two drugs, a noncompartmental model was used. Elimination half-lives of amoxicillin and clavulanic acid were not significantly different, i.e. 0.73 and 0.67 h respectively. The mean maximal plasma concentrations of amoxicillin and clavulanic acid were 3.14 and 2.42 mg/L, and these were reached after 1.19 and 0.88 h respectively. The mean p.o. bioavailability was found to be 22.8% for amoxicillin and 44.7% for clavulanic acid.     

Effects of an adapted intravenous amiodarone treatment protocol in horses with atrial fibrillation

REASON FOR PERFORMING STUDY: Good results have been obtained with a human amiodarone (AD) i.v. protocol in horses with chronic atrial fibrillation (AF) and a pharmacokinetic study is required for a specific i.v. amiodarone treatment protocol for horses. OBJECTIVES: To study the efficacy of this pharmacokinetic based i.v. AD protocol in horses with chronic AF. METHODS: Six horses with chronic AF were treated with an adapted AD infusion protocol. The protocol consisted of 2 phases with a loading dose followed by a maintenance infusion. In the first phase, horses received an infusion of 6.52 mg AD/kg bwt/h for 1 h followed by 1.1 mg/kg bwt/h for 47 h. In the second phase, horses received a second loading dose of 3.74 mg AD/kg bwt/h for 1 h followed by 1.31 mg/kg bwt/h for 47 h. Clinical signs were monitored, a surface ECG and an intra-atrial electrogram were recorded. AD treatment was discontinued when conversion or any side effects were observed. RESULTS: Three of the 6 horses cardioverted successfully without side effects. The other 3 horses did not convert and showed adverse effects, including diarrhoea. In the latter, there were no important circulatory problems, but the diarrhoea continued for 10-14 days. The third horse had to be subjected to euthanasia because a concomitant Salmonella infection worsened the clinical signs. CONCLUSION: The applied treatment protocol based upon pharmacokinetic data achieved clinically relevant concentrations of AD and desethylamiodarone. POTENTIAL RELEVANCE: Intravenous AD has the potential to be an alternative pharmacological treatment for AF in horses, although AD may lead to adverse drug effects, particularly with cumulative dosing.     

In vitro susceptibility of six isolates of equine herpesvirus 1 to acyclovir, ganciclovir, cidofovir, adefovir, PMEDAP and foscarnet

Equine herpesvirus 1 (EHV-1) is an important equine pathogen that causes respiratory disease, abortion, neonatal death and paralysis. Although vaccines are available, they are not fully protective and outbreaks of disease may occur in vaccinated herds. Therefore, there is an urgent need for effective antiviral treatment. For three abortigenic (94P247, 97P70 and 99P96) and three neuropathogenic isolates (97P82, 99P136 and 03P37), the effect of acyclovir, ganciclovir, cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) and foscarnet on plaque number was studied. Additionally, for isolate 97P70, the effect on plaque size was investigated. Ganciclovir was most potent in reducing plaque number, followed by PMEDAP and acyclovir. Adefovir and cidofovir were less effective and foscarnet was the least effective compound. There were no differences detected for acyclovir, ganciclovir, adefovir and PMEDAP between the abortigenic and neuropathogenic isolates. One abortigenic isolate (99P96) was more susceptible to cidofovir and two neuropathogenic isolates (99P136 and 03P37) were less susceptible to foscarnet. For isolate 97P70, all compounds resulted in a significant reduction of plaque size. The most remarkable effect was observed for cidofovir. It was 40-fold more effective in reducing plaque size than in reducing plaque number. In conclusion, ganciclovir was the most potent compound and therefore, may be a valuable candidate for the treatment of EHV-1 infections in horses. The antiviral effect of foscarnet on plaque number was highly dependent on the viral isolate tested. Therefore, it is no valuable antiviral for the treatment of herpesvirus-infections. Cidofovir, although less effective in reducing plaque number, had a strong effect on plaque size.     

Crop yield and SOC responses to biochar application were dependent on soil texture and crop type in southern Quebec,Canada

Changes to soil nutrient availability and increases for crop yield and soil organic C (SOC) concentration on biochar‐amended soil under temperate climate conditions have only been reported in a few publications. The objective of this work was to determine if biochar application rates up to 20 Mg ha^?1 affect nutrient availability in soil, SOC stocks and yield of corn (Zea mays L.), soybean (Glycine max L.), and switchgrass (Panicum virgatum L.) on two coarse‐textured soils (loamy sand, sandy clay loam) in S Quebec, Canada. Data were collected from field experiments for a 3‐y period following application of pine wood biochar at rates of 0, 10, and 20 Mg ha^?1. For corn plots, at harvest 3 y after biochar application, 20 Mg biochar ha^?1 resulted in 41.2% lower soil NH on the loamy sand; the same effect was not present on the sandy clay loam soil. On the loamy sand, 20 Mg biochar ha^?1 increased corn yields by 14.2% compared to the control 3 y after application; the same effect was not present on the sandy clay loam soil. Biochar did not alter yield or nutrient availability in soil on soybean or switchgrass plots on either soil type. After 3 y, SOC concentration was 83 and 258% greater after 10 and 20 Mg ha^?1 biochar applications, respectively, than the control in sandy clay loam soil under switchgrass production. The same effect was not present on the sandy clay loam soil. A 67% higher SOC concentration was noted with biochar application at 20 Mg ha^?1 to sandy clay loam soil under corn.     

Phylogeny of five predominant pospiviroid species in Belgium

In Belgium pospiviroids are routinely detected in various hosts. The most frequently found pospiviroids are: Citrus exocortis viroid (CEVd), Chrysanthemum stunt viroid (CSVd), Potato spindle tuber viroid (PSTVd), Tomato apical stunt viroid (TASVd) and Tomato chlorotic dwarf viroid (TCDVd). Apart from the high incidence of pospiviroids in latently-infected ornamentals, viroids have also been found in plants where they cause disease: PSTVd and TCDVd in tomatoes and CSVd in chrysanthemum. In order to gain more epidemiological data on these infections, this study has conducted phylogenetic analyses of Belgian isolates for each of these five pospiviroid species. PSTVd and CEVd-isolates show a clustering depending on host plant identity. This was not observed for TCDVd and TASVd. A very high degree of sequence similarity was noticeable for CSVd-isolates from various hosts. During the past decade, PSTVd and CSVd-infected mother plants have been systematically eradicated in Belgium after positive detection results, also when found in symptomless plants, leading to a decreased trend of these quarantine pests in the past few years. However, other non-quarantine pospiviroid species are still ubiquitously present in many ornamentals. Since these pospiviroids can be equally harmful to crops as the two quarantine pests PSTVd and CSVd, there is still a risk that transmission occurs from symptomless-infected ornamental plants to economically important crops in Belgium such as tomato, pepper and chrysanthemum.     

Protection against enzootic pneumonia of pigs: intraperitoneal inoculation with live LKR strain of Mycoplasma hyopneumoniae

Pigs obtained from a mycoplasma-free piggery were randomised into 4 groups of 9. Groups 1 and 2 were injected by the intraperitoneal route with liquid culture of the LKR strain of Mycoplasma hyopneumoniae. Group 1 was injected once and group 2 twice. Group 3 was made up of pigs inoculated by the intranasal route with the virulent Beaufort strain of M. hyopneumoniae; they served as the source of infection for the challenge. Group 4 were uninfected, uninjected controls. Six weeks after the last injection, groups from 1 to 4 were placed in contact. Seven of the pigs in the 1-dose group and 6 in the 2-dose group were free of lesions at necropsy 6 weeks after challenge. Of the two pigs with lesions in the 1-dose group one had only a small lesion but the other had extensive lesions; it had not shown an antibody response after injection of culture. The lesions in the 3 pigs in the 2-dose group were all small. All 9 control pigs had lesions which varied from medium to large in size. The difference in the incidence of pneumonia between the injected and control groups was significant (P less than 0.05) and the proportion of severely affected pigs in the vaccinated groups was significantly lower (P greater than 0.01). There was no difference between those given one dose of vaccine and those receiving 2 doses.     

Pharmacokinetics and oral bioavailability of pentoxyfylline in broiler chickens

The pharmacokinetic properties of pentoxyfylline and its metabolites were determined in healthy chickens after single intravenous and oral dosage of 100 mg/kg pentoxyfylline. Plasma concentrations of pentoxyfylline and its metabolites were determined by a validated high-performance liquid chromatographic method. After intravenous (i.v.) and oral (p.o.) administration, the plasma concentration-time curves were best described by a one-compartment open model. The mean elimination half-life (t(1/2el)) of pentoxyfylline was 1.05 h, total body clearance 1.90 L/h x kg, volume of distribution 2.40 L/kg and the mean residence time was 2.73 h, after i.v. administration. After oral dosing, mean maximal plasma concentration of pentoxyfylline was 4.01 microg/mL and the interval from p.o. administration until maximum concentration was 1.15 h. The mean oral bioavailability was found to be 28.2%. Metabolites I, IV and V were present in chicken plasma after both i.v. and p.o. administration, with metabolite V being the most dominant.     

Antipyretic effect of oral sodium salicylate after an intravenous E. coli LPS injection in broiler chickens

A study was set up to investigate the influence of sodium salicylate on fever and acute phase reaction after lipopolysaccharide (LPS) injection in broiler chickens. An acute phase reaction was provoked through the intravenous injection of Escherichia coli LPS. Four oral doses of sodium salicylate were tested. Apart from body temperature, other inflammation indices, such as plasma corticosterone and ceruloplasmin, serum thromboxane B2 and zinc concentrations were monitored. Intravenous LPS induced a fever of about 1 degree C. A dose-dependent attenuation of the fever response of the chickens in the salicylate treated groups was observed. LPS-injected chickens also showed elevated plasma corticosterone and ceruloplasmin, while serum thromboxane and zinc concentrations decreased. Except for thromboxane B2, no linear relationship with increasing salicylate dose could be shown for the other blood variables. These data confirm that sodium salicylate is an effective antipyretic agent after injection of LPS in chickens, if used at an appropriate dosage. No dose-related change could be found for the other inflammation indices.