Does the rate of fat deposition influence the pharmacokinetic disposition of subcutaneously administered moxidectin and ivermectin in pigs?

Body condition has been shown to affect the pharmacokinetics of subcutaneously administered macrocyclic lactone anthelmintics but the underlying mechanism is unknown. This study examined the effect of different rates of fat deposition on the pharmacokinetics of moxidectin (MXD) and ivermectin (IVM). All animals initially received a diet with a high linoleic acid content for 7 weeks. One group of animals then received a normal grower diet while the other half received a maintenance ration. Within each diet group, animals were treated with either IVM (n = 4) or MXD (n = 4) or remained as untreated controls (n = 2). There was no difference in the proportion of linoleic acid between the drug treated groups and the untreated controls at any time throughout the study. At 4 and 9 weeks after treatment there was a significantly lower proportion of linoleic acid in the pigs fed the normal ration indicating a greater fat deposition in these animals compared with those that received the maintenance diet. There was an increased persistence of MXD in the plasma of pigs fed the normal ration compared with those fed the maintenance ration. No differences were seen in the kinetic disposition of IVM between pigs fed the maintenance or normal ration. Reducing the rate of fat deposition influenced the pharmacokinetic disposition of the highly lipophilic MXD but did not influence the pharmacokinetic disposition of the less lipophilic IVM.     

Comparative plasma disposition kinetics of ivermectin, moxidectin and doramectin in cattle

The persistence of the broad-spectrum antiparasitic activity of endectocide compounds relies on their disposition kinetics and pattern of plasma/tissues exchange in the host. This study evaluates the comparative plasma disposition kinetics of ivermectin (IVM), moxidectin (MXD) and doramectin (DRM) in cattle treated with commercially available injectable formulations. Twelve (12) parasite-free male Hereford calves (180–210 kg) grazing on pasture were allocated into three groups of four animals each. Animals in each group received either IVM (Ivomec 1%, MSD AGVET, Rahway, NJ, USA), MXD (Cydectin 1%, American Cyanamid, Wayne, NJ, USA) or DRM (Dectomax 1%, Pfizer Inc., New York, NY, USA) by subcutaneous injection at a dose of 200 μg/kg. Jugular blood samples were collected from 1 h up to 80 days post-treatment, and plasma extracted, derivatized and analysed by high performance liquid chromatography (HPLC) using fluorescence detection. The parent molecules were detected in plasma between 1 h and either 70 (DRM) or 80 (IVM and MXD) days post-treatment. The absorption of MXD from the site of injection was significantly faster (absorption half-life (t_½ab) = 1.32 h) than those of IVM (t_½ab= 39.2 h) and DRM (t_½ab= 56.4 h). MXD peak plasma concentration (C_max) was reached significantly earlier (8.00 h) compared to those of IVM and DRM (4–6 days post-treatment). There were no differences on C_max values; the area under the concentration–time curve (AUC) was higher for IVM (459 ng.d/mL) and DRM (627 ng.d/mL) compared to that of MXD (217 ng.d/mL). The mean plasma residence time was longer for MXD (14.6 d) compared to IVM (7.35 d) and DRM (9.09 d). Unidentified metabolites were detected in plasma; they accounted for 5.75% (DRM), 8.50% (IVM) and 13.8% (MXD) of the total amount of their respective parent drugs recovered in plasma. The comparative plasma disposition kinetics of IVM, MXD and DRM in cattle, characterized over 80 days post-treatment under standardized experimental conditions, is reported for the first time.     

Pharmacokinetics of moxidectin and ivermectin following intravenous injection in pigs with different body compositions

Macrocyclic lactones (ML) are highly effective anthelmintics that provide a long protective period after administration because of their extensive distribution into fat. This study examined whether the body composition of the animal at the time of treatment had any influence on the pharmacokinetics of two MLs, moxidectin (MOX) and ivermectin (IVM). 'Fat' and 'lean' lines of pigs were established using two different diets, with weekly determination of liveweight and backfat thickness confirming the difference in body condition between the groups. Blood samples were taken at regular intervals following i.v. injection of IVM or MOX at a dose of 300 microg/kg and the plasma was analysed using fluorescence high performance liquid chromatography (HPLC) to determine the concentration of IVM or MOX in the samples. Regardless of body composition IVM and MOX kinetics were very different with MOX having a greater apparent volume of distribution, longer distribution and elimination half-lives and a slower clearance rate than IVM, which led to MOX being detectable in plasma for >40 days compared with only 8-10 days for IVM. Altering body composition had no detectable influence on the kinetic disposition of IVM in this study. In contrast, although there was no difference in AUC or the volume of distribution, MOX was distributed within and eliminated from the lean animals more rapidly than from the fat animals.     

The comparative serum disposition kinetics of subcutaneous administration of doramectin, ivermectin and moxidectin in the Australian Merino sheep

This study evaluates the comparative serum disposition kinetics of injectable formulations of doramectin (DRM), ivermectin (IVM) and moxidectin (MXD) in Australian Merino sheep. Thirty-six, 2-year-old sheep were allocated by weight into six groups of six animals. Animals in each group received 200 microg/kg of DRM, MXD, IVM or a combination of two of these drugs by subcutaneous (s.c.) injection. Blood was collected at designated intervals (between 1 h and 40 days after treatment) and the serum analysed by high performance liquid chromatography (HPLC) using fluorescence detection. The results indicated that MXD administration produced a significantly higher maximum serum concentration and a more rapid absorption as compared with DRM and IVM. MXD and DRM had a significantly larger area under the concentration vs. time curve (AUC) than IVM, suggesting a more persistent effect for the former two products in sheep. The AUC for DRM was significantly higher when administered alone as compared with that observed when given in combination with MXD or IVM, suggesting preferential elimination of DRM compared with IVM and MXD from concurrent s.c. administration.     

Comparison of the pharmacokinetics of moxidectin (Equest®) and ivermectin (Eqvalan®) in horses

A study was undertaken in order to evaluate and compare plasma disposition kinetic parameters of moxidectin and ivermectin after oral administration of their commercially available preparations in horses. Ten clinically healthy adult horses, weighing 390-446 kg body weight (b.w.), were allocated to two experimental groups of five horses. Group I was treated with an oral gel formulation of moxidectin (MXD) at the manufacturers recommended therapeutic dose of 0.4 mg/kg bw. Group II was treated with an oral paste formulation of ivermectin (IVM) at the manufacturers recommended dose of 0.2 mg/kg b.w. Blood samples were collected by jugular puncture at different times between 0.5 h and 75 days post-treatment. After plasma extraction and derivatization, samples were analysed by HPLC with fluorescence detection. Computerized kinetic analysis was carried out. The parent molecules were detected in plasma between 30 min and either 30 (IVM) or 75 (MXD) days post-treatment. Both drugs showed similar patterns of absorption and no significant difference was found for the time corresponding to peak plasma concentrations or for absorption half-life. Peak plasma concentrations (Cmax) of 70.3+/-10.7 ng/mL (mean +/- SD) were obtained for MXD and 44.0+/-23.1 ng/mL for IVM. Moreover, the values for area under concentration-time curve (AUC) were 363.6+/-66.0 ng x d/mL for the MXD treated group, and 132.7+/-47.3 ng x d/mL for the IVM treated group. The mean plasma residence times (MRT) were 18.4+/-4.4 and 4.8+/-0.6 days for MXD and IVM treated groups, respectively. The results showed a more prolonged residence of MXD in horses as demonstrated by a four-fold longer MRT than for IVM. The longer residence and the higher concentrations found for MXD in comparison to IVM could possibly explain a more prolonged anthelmintic effect. It is concluded that in horses the commercial preparation of MXD presents a pharmacokinetic profile which differs significantly from that found for a commercial preparation of IVM. To some extent these results likely reflect differences in formulation and doses.     

Plasma pharmacokinetics and faecal excretion of ivermectin, doramectin and moxidectin following oral administration in horses

The present study was carried out to investigate whether the pharmacokinetics of avermectins or a milbemycin could explain their known or predicted efficacy in the horse. The avermectins, ivermectin (IVM) and doramectin (DRM), and the milbemycin, moxidectin (MXD), were each administered orally to horses at 200 microg/kg bwt. Blood and faecal samples were collected at predetermined times over 80 days (197 days for MXD) and 30 days, respectively, and plasma pharmacokinetics and faecal excretion determined. Maximum plasma concentrations (Cmax) (IVM: 21.4 ng/ml; DRM: 21.3 ng/ml; MXD: 30.1 ng/ml) were obtained at (tmax) 7.9 h (IVM), 8 h (DRM) and 7.9 h (MXD). The area under the concentration time curve (AUC) of MXD (92.8 ng x day/ml) was significantly larger than that of IVM (46.1 ng x day/ml) but not of DRM (53.3 ng x day/ml) and mean residence time of MXD (17.5 days) was significantly longer than that of either avermectin, while that of DRM (3 days) was significantly longer than that of IVM (2:3 days). The highest (dry weight) faecal concentrations (IVM: 19.5 microg/g; DRM: 20.5 microg/g; MXD: 16.6 microg/g) were detected at 24 h for all molecules and each compound was detected (> or = 0.05 microg/g) in faeces between 8 h and 8 days following administration. The avermectins and milbemycin with longer residence times may have extended prophylactic activity in horses and may be more effective against emerging and maturing cyathostomes during therapy. This will be dependent upon the relative potency of the drugs and should be confirmed in efficacy studies.     

A comparative kinetic study of ivermectin and moxidectin in lactating camels (Camelus dromedarius).

The plasma and milk kinetics of ivermectin (IVM) and moxidectin (MXD) was evaluated in lactating camels treated subcutaneously (0.2 mg kg(-1)) with commercially available formulations for cattle. Blood and milk samples were taken concurrently at predetermined times from 12 h up to 60 days post-administration. No differences were observed between plasma and milk kinetics of IVM, while substantial differences were noted between plasma and milk profiles of MXD in that both the maximal concentration (Cmax) and the area under concentrations curves (AUC) were three to four-fold higher for milk than for plasma. The time (Tmax) to reach Cmax was significantly faster for MXD (1.0 day) than that for IVM (12.33 days). The Cmax and the AUC were significantly higher for MXD (Cmax = 8.33 ng ml(-1); AUC = 70.63 ng day ml(-1)) than for IVM (Cmax = 1.79 ng ml(-1); AUC = 30.12 ng day ml(-1)) respectively. Drug appearance in milk was also more rapid for MXD (Tmax = 3.66 days) compared to IVM (Tmax = 17.33 days). The extent of drug exchange from blood to milk, expressed by the AUCmilk/AUCplasma ratio, was more than three-fold greater for MXD (4.10) compared to that of IVM (1.26), which is consistent with the more lipophilic characteristic of MXD. However, the mean residence time (MRT) was similar in both plasma and milk for each drug.     

Licking induced changes to the pattern of moxidectin milk elimination after topical treatment in dairy cows

Pour-on administration of the macrocyclic lactones anti-parasitic compounds in beef and dairy cattle is now worldwide accepted. However, the information available on their milk excretion pattern, after topical administration is rather limited. Additionally, the cattle licking behaviour has been proven to affect the kinetics of these anti-parasitic compounds. The purpose of this study was to investigate the influence of the natural licking behaviour on the plasma and milk disposition of moxidectin (MXD), topically administered (500 μg/kg) in lactating dairy cows. Ten lactating Holstein dairy cows (705 kg body weight) were allocated into two experimental groups ( n  = 5). The licking was prevented during 5 days postadministration in animals in group I, and the remaining cows (group II) were allowed to lick freely. MXD concentrations profiles were measured in plasma and milk over 15 days posttreatment. The licking restriction period caused marked changes in MXD disposition kinetics both in plasma and milk. Both plasma and milk MXD concentrations (partial AUC 0–5 days) were significantly lower ( P  < 0.05) in licking-restricted cows. After the 5-day of restriction period, the animals were allowed to lick freely, which permitted the oral ingestion of MXD, situation clearly reflected both in plasma profile and milk excretion pattern. Despite the enhanced MXD milk concentrations measured in free-licking cows, drug concentrations did not reach the maximum MXD residues limit.     

猪背膘中NADPH生成酶的活性与瘦肉率关系的初步研究

试验选择湖北白猪断奶仔猪48头,测定150和180日龄的活体背膘厚及背膘脂肪组织中NADPH生成酶的活性。180日龄随机屠宰36头。对背膘中4种NADPH生成酶的活性与活体背膘厚及胴体性状进行相关分析,结果表明:150和180日龄4种酶的总活性与活体背膘厚、胴体背膘厚及肥肉率呈正相关;与胴体瘦肉率呈负相关。说明4种NADPH生成酶的活性高时,猪的活体背膘厚、胴体肥肉率提高,瘦肉率降低。文中还给出了用酶活性估测瘦肉率的回归方程。研究结果表明猪背膘中4种NADPH生成酶的活性可以作为选择瘦肉型猪瘦肉率性状的辅助指标。     

Bioequivalence of ivermectin formulations in pigs and cattle

The vehicle in which endectocide compounds are formulated plays a relevant role in their absorption kinetics and resultant systemic availability. The pharmaceutical bioequivalence and comparative plasma disposition kinetics of ivermectin (IVM), following the subcutaneous administration of two injectable formulations to pigs and cattle were investigated using parallel experimental designs. Sixteen parasite-free male Duroc Jersey-Yorkshire crossbred pigs (90-110 kg) (Expt 1) and 16 parasite-free male Holstein calves (100-120 kg) (Expt 2) were divided into two groups and treated subcutaneously at either 300 (pigs) or 200 (calves) microg/kg with two different propylene glycol/glycerol formal (60: 40) based IVM formulations; in both experiments pigs or calves in Group A received the test (IVM-TEST) formulation and those in Group B were treated with the reference formulation (IVM-CONTROL). Heparinized blood samples were taken from 0 h up to either 20 (pigs) or 30 (calves) days post-treatment and plasma was extracted, derivatized and analysed by high performance liquid chromatography (HPLC) using fluorescence detection. Early detection of IVM (12 h) with a peak plasma concentration (C(max)) between 33 and 39 ng/mL was observed in pigs. The drug was detected in plasma up to 20 days post-administration of either formulation, resulting in elimination half-lives between 3.47 and 3.80 days. There were no differences between the IVM-TEST and IVM-CONTROL formulations in the kinetic parameters (except t(max)) obtained in pigs. IVM was detected in plasma between 12 h and 30 days post-administration of both formulations under investigation in cattle. The plasma disposition kinetics of IVM in calves was similar following treatment with both formulations. C(max) values (between 40.5 and 46.4 ng/mL) were achieved at 2 days post-administration of both formulations. None of the estimated kinetic parameters were statistically different between drug formulations. The injectable IVM formulations investigated were bioequivalent after their subcutaneous administration to both pigs and calves at recommended dose rates.     

Plasma thyroid hormones, growth and carcass measurements of genetically obese and lean pigs as influenced by thyroprotein supplementation

A 2 X 2 factorial arrangement with two genotypes of pigs (genetically obese and lean) and two dietary treatments (basal, a 16% protein corn-soybean meal standard grower diet, and basal +220 ppm thyroprotein as iodinated casein) was used. The 28 gilts were housed individually and fed ad libitum from 121 d of age until slaughtered at 99 kg body weight. Compared with lean pigs, genetically obese pigs had significantly lower average daily gain and gain/feed, greater backfat thickness, smaller loin eye area, shorter carcass length and lower circulating plasma triiodothyronine (T3) concentration. However, both total plasma and free thyroxine (T4) concentrations were similar comparing obese and lean pigs. Supplementation with thyroprotein increased circulating plasma concentration of both total and free T4 and produced interactions with genotype in affecting daily gain and gain/feed of pigs. Thyroprotein reduced both daily gain and gain/feed in obese pigs, but increased daily gain and gain/feed in lean pigs. It is suggested, similar to the case with obese mice, that heat production of our genetically obese pigs may be more sensitive to thyroprotein administration compared with similar treatment of lean animals.     

The effects of different ages and dosages on the plasma disposition and hair concentration profile of ivermectin following pour-on administration in goats

Gokbulut, C., Cirak, V.Y., Senlik, B., Aksit, D., McKellar, Q.A. The effects of different ages and dosages on the plasma disposition and hair concentration profile of ivermectin following pour‐on administration in goats. J. vet. Pharmacol. Therap. 34 , 70–75. The effects of different ages and dosages on the plasma disposition and hair degradation of ivermectin (IVM) were investigated following pour‐on administration in goats. Twenty‐eight female Saanen goats allocated into two groups of 14 animals according to their ages as young (5–6 months old) and old (12–24 months old) groups. Each age group was divided into two further of seven goats and administered pour‐on formulation of IVM topically at the in recommended dosage rate of 0.5 mg/kg bodyweight The recommended cattle dosages rate of 0.5 mg/kg or at the higher dosage of 1.0 mg/kg. Blood samples were collected at various times between 1 h and 40 days. In addition, hair samples (>0.01 g) were collected using tweezers from the application sites and far from application sites of the all animals throughout the blood sampling period. The plasma and hair samples were analyzed by high performance liquid chromatography (HPLC) using fluorescence detection following solid and liquid phase extractions, respectively. Dose‐ and age‐dependent plasma disposition of IVM were observed in goats after pour‐on administration. In addition, relatively high concentration and slow degradation of IVM in hair samples collected from the application site and far from the application site were observed in the present study. The differences between young and old goats are probably related to differences in body condition and/or lengths of haircoat. The systemic availability of IVM following pour‐on administration is relatively much lower than after oral and subcutaneous administrations but the plasma persistence was prolonged. Although, the longer persistence of IVM on hairs on the application site may prolong of efficacy against ectoparasites, the poor plasma availability could result in subtherapeutic plasma concentrations, which may confer the risk of resistance development in for internal parasites after pour‐on administration in goats.     

Effects of dietary iodine value product on growth performance and carcass fat quality of finishing pigs

A total of 120 barrows (initial BW = 47.9 ± 3.6 kg; PIC 1050) were used in an 83-d study to determine the effects of dietary iodine value (IV) product (IVP) on growth performance and fat quality. Pigs were blocked by BW and randomly allotted to 1 of 6 treatments with 2 pigs per pen and 10 pens per treatment. Dietary treatments were fed in 3 phases and formulated to 3 IVP concentrations (low, medium, and high) in each phase. Treatments were 1) corn-soybean meal control diet with no added fat (low IVP), 2) corn-extruded expelled soybean meal (EESM) diet with no added fat (medium IVP), 3) corn-soybean meal diet with 15% distillers dried grains with solubles and choice white grease (DDGS + CWG; medium IVP), 4) corn-soybean meal diet with low CWG (medium IVP), 5) corn-EESM diet with 15% DDGS (high IVP), and 6) corn-soybean meal diet with high CWG (high IVP). On d 83, pigs were slaughtered and backfat and jowl fat samples were collected and analyzed. The calculated and analyzed dietary IVP values were highly correlated (r(2) = 0.86, P < 0.01). Pigs fed the control diet, EESM, or high CWG had greater (P < 0.05) ADG than pigs fed EESM + DDGS. Pigs fed the control diet had greater (P < 0.05) ADFI than pigs fed all other diets. Pigs fed EESM + DDGS and high CWG had improved (P < 0.05) G:F compared with pigs fed the control diet or DDGS + CWG. Pigs fed diets with DDGS had greater (P < 0.05) backfat and jowl fat IV, C18:2n-6, and PUFA and less SFA than pigs fed all other treatments. Pigs fed EESM had greater (P < 0.05) backfat and jowl fat IV, C18:2n-6, and PUFA than pigs fed the control diet, low CWG, or high CWG. Pigs fed low CWG or high CWG had greater (P < 0.05) jowl fat IV than control pigs. Feeding ingredients high in unsaturated fatty acids, such as DDGS and EESM, had a greater impact on fat IV than CWG, even when diet IVP was similar. Therefore, IVP was a poor predictor of carcass fat IV in pigs fed diets with different fat sources and amounts of unsaturated fats formulated with similar IVP. Dietary C18:2n-6 content was a better predictor of carcass fat IV than diet IVP.     

Moxidectin in cattle: correlation between plasma and target tissues disposition

The time of parasite exposure to active drug concentrations determines the persistence of the antiparasitic activity of endectocide compounds. This study evaluates the disposition kinetics of moxidectin (MXD) in plasma and in different target tissues following its subcutaneous (s.c.) administration to cattle. Eighteen male, 10-month old Holstein calves weighing 120-140 kg were subcutaneously injected in the shoulder area with a commercially available formulation of MXD (Cydectin 1%, American Cyanamid, Wayne, NJ, USA) at 200 micrograms/kg. Two treated calves were killed at each of the following times post-treatment: 1, 4, 8, 18, 28, 38, 48, 58 and 68 days. Abomasal and small intestine mucosal tissue and fluids, bile, faeces, lung, skin and plasma samples were collected, extracted, derivatized and analysed to determine MXD concentrations by high performance liquid chromatography (HPLC) with fluorescence detection. MXD was extensively distributed to all tissues and fluids analysed, being detected (concentrations > 0.1 ng/g; ng/mL) between 1 and 58 days post-treatment. MXD peak concentrations were attained during the first sampling day. MXD maximum concentration (Cmax) values ranged from 52.9 (intestinal mucosa) up to 149 ng/g (faeces). The mean residence time (MRT) in the different tissues and fluids ranged from 6.8 (abomasal mucosa) up to 11.3 (bile) days. MXD concentrations in abomasal and intestinal mucosal tissue were higher than those detected in plasma; however, there was a high correlation between MXD concentrations observed in plasma and those detected in both gastrointestinal mucosal tissues. MXD concentrations were markedly greater in the mucosa than in its respective digestive fluid (P < 0.01). MXD concentrations in skin were higher than those found in plasma (P < 0.01). Drug concentrations recovered in the dermis were greater than those detected in the hypodermal tissue (P < 0.05). Large concentrations of MXD were excreted in bile and faeces. These findings may contribute to an understanding of the relationship between the kinetic behaviour and the persistence of the antiparasite activity of MXD against different ecto-endoparasites in cattle.     

Effects of increasing choice white grease in corn- and sorghum-based diets on growth performance, carcass characteristics, and fat quality characteristics of finishing pigs

A total of 120 pigs (60 barrows and 60 gilts; TR4 × PIC 1050; 54.4 kg initial BW) were used in an 83-d study to evaluate the effects of added fat in corn- and sorghum-based diets on growth performance, carcass characteristics, and carcass fat quality. Treatments were arranged in a 2 × 3 factorial with grain source (corn or sorghum) and added fat (0, 2.5, or 5% choice white grease; CWG) as factors. There were 2 pigs (1 barrow and 1 gilt) per pen and 10 replicate pens per treatment. Pigs and feeders were weighed on d 14, 22, 39, 53, 67, and 83 to calculate ADG, ADFI, and G:F. At the end of the trial, pigs were slaughtered and jowl fat and backfat samples were collected and analyzed for fatty acid profile. No interactions were observed for growth performance. Pigs fed sorghum-based diets had greater (P < 0.01) ADG than pigs fed corn-based diets. Adding CWG improved (linear, P < 0.01) ADG. Pigs fed corn-based diets tended to have greater (P < 0.09) carcass yield, 10th-rib backfat, and percentage lean than pigs fed sorghum-based diets. Adding CWG increased (linear, P = 0.02) 10th-rib backfat, tended to increase (linear, P = 0.08) HCW, and tended to decrease (linear, P = 0.07) percentage lean. There was no grain source × fat level interaction for iodine value (IV) in backfat, but an interaction (P = 0.03) was observed for IV in jowl fat. Adding CWG increased (P < 0.01) IV in jowl fat for pigs fed sorghum- and corn-based diets; however, the greatest increase was between 0 and 2.5% CWG in sorghum-based diets and between 2.5 and 5% CWG in corn-based diets. Pigs fed corn-based diets had less (P = 0.01) C18:1 cis-9 and MUFA but greater (P = 0.01) C18:2n-6, PUFA, and backfat IV than pigs fed sorghum-based diets. Increasing CWG in the diet increased (linear, P = 0.01) backfat IV. Of the 2 fat depots, backfat generally had a reduced IV than jowl fat. In summary, feeding sorghum-based diets reduced carcass fat IV and unsaturated fats compared with corn-based diets. As expected, adding CWG increased carcass fat IV regardless of the cereal grain in the diet.     

Comparative pharmacokinetic and pharmacodynamic response of single and double intraruminal doses of ivermectin and moxidectin in nematode-infected lambs

Abstract

AIMS: To compare the pharmacokinetics, distribution and efficacy (pharmacodynamic response) of intraruminal ivermectin (IVM) and moxidectin (MXD) administered at 0.2 and 0.4?mg/kg to naturally nematode-infected lambs, and to determine the ex vivo accumulation of these anthelmintics by Haemonchus contortus.

METHODS: Romney Marsh lambs, naturally infected with IVM-resistant H. contortus, were allocated to treatment groups based on faecal nematode egg counts. They received 0.2 or 0.4?mg/kg IVM or MXD (n=10 per group), or no treatment (Control; n=6), on Day 0. Samples from four animals from each treatment group, including abomasal parasites, were obtained on Day 1. Plasma samples were also collected from Day 0 to 14, and a faecal egg count reduction test (FECRT) and a controlled efficacy trial were carried out on Day 14. Concentrations of IVM and MXD in plasma, in abomasal and intestinal tissues and in H. contortus were evaluated by high-performance liquid chromatography. Additionally, the ex vivo drug accumulation of IVM and MXD by H. contortus was determined.

RESULTS: Peak plasma concentrations and the area under the concentration vs. time curve for both IVM and MXD were higher for 0.4 than 0.2?mg/kg treatments (p<0.05), but there were no differences for other parameters. Concentrations of IVM and MXD in the gastrointestinal target tissues and in H. contortus were higher compared to those measured in plasma. Concentrations of both drugs in H. contortus were correlated with those observed in the abomasal content (r=0.86; p<0.0001). The exposure of H. contortus to IVM and MXD was related to the administered dose. Mean FECRT and efficacy for removal of adult H. contortus was 0% for IVM at 0.2 and 0.4?mg/kg. For MXD, FECRT were >95% for both treatments, and efficacy against H. contortus was 85.1% and 98.1% for 0.2 and 0.4?mg/kg, respectively. The ex vivo accumulation of IVM and MXD in H. contortus was directly related to the drug concentration present in the environment and was influenced by the duration of exposure.

CONCLUSION: Administration of IVM and MXD at 0.4 compared with 0.2?mg/kg accounted for enhanced drug exposure in the target tissues, as well as higher drug concentrations within resistant nematodes. The current work is a further contribution to the evaluation of the relationship between drug efficacy and basic pharmacological issues in the presence of resistant parasite populations.     

Breed-related plasma disposition of ivermectin following subcutaneous administration in Kilis and Damascus goats

Many factors related with drug and animals affect the plasma disposition of endectocides including ivermectin (IVM). The aim of the present study was to investigate the breed differences in pharmacokinetics of IVM in goats following subcutaneous administration. Two different goat breeds (Kilis and Damascus goats) were allocated into two treatment groups with respect to breed. The injectable formulation of IVM was administered subcutaneously at a dose rate of 0.2 mg/kg bodyweight. Blood samples were collected before treatment and at various times between 1 h and 40 days after treatment and the plasma samples were analysed by high performance liquid chromatography (HPLC) using fluorescence detection. The results indicated that the plasma disposition of IVM was substantially affected by breed differences following subcutaneous administration in goats. The last detectable plasma concentration (t_last) of IVM was significantly later in Kilis goats (38.33 days) compared with Damascus goats (22.50 days). Although, there were no significant differences on C_max (10.83 ng/ml vs. 10.15 ng/ml) and t_max (2.75 days vs. 2.33 days) values; the area under the concentration–time curve-AUC (110.26 ng.d/ml vs. 73.38 ng.d/ml) the terminal half-life-t_1/2λz (5.65 days vs. 3.81 days) and the mean plasma residence time-MRT (9.31 days vs. 6.35 days) were significantly different in Kilis goats compared with Damascus goats, respectively. The breed-related difference observed on the plasma disposition of IVM between Kilis and Damascus goats could be attributable to different excretion pattern or specific anatomical and/or physiological characteristics such as body fat composition of each breed.     

Comparative plasma and milk dispositions,faecal excretion and efficacy of per os ivermectin and pour‐on eprinomectin in horses

The horse milk gains increasing interest as a food product for sensitive consumers, such as children with food allergies or elderly people. We investigated the plasma and milk disposition, faecal excretion and efficacy of per os ivermectin (IVM) and pour‐on eprinomectin (EPM) in horses. Ten mares were divided into two groups. The equine paste formulation of IVM and bovine pour‐on formulation of EPM were administered orally and topically at dosage of 0.2 and 0.5 mg/kg bodyweight. Blood, milk and faecal samples were analysed using high‐performance liquid chromatography. The plasma concentration and persistence of IVM were significantly greater and longer compared with those of EPM. Surprisingly, EPM displayed a much higher disposition rate into milk (AUC_milk/plasma: 0.48) than IVM (AUC_milk/plasma: 0.19). IVM exhibited significantly higher faecal excretion (AUC_faeces: 7148.54 ng·d/g) but shorter faecal persistence (MRT_faeces: 1.17 days) compared with EPM (AUC_faeces: 42.43 ng·d/g and MRT_faeces: 3.29 days). Faecal strongyle egg counts (EPG) were performed before and at weekly intervals after treatment. IVM reduced the EPG by 96–100% for up to 8 weeks, whereas the reduction in the EPM group varied from 78 to 99%. In conclusion, due to the relatively low excretion in milk, EPM and IVM may be used safely in lactating mares if their milk is used for human consumption. Nevertheless, much lower plasma and faecal availabilities of EPM could result in subtherapeutic concentrations, which may increase the risk of drug resistance in nematodes after pour‐on EPM administration compared with per os IVM.     

Effect of Lactation Diet Fat Level on Sow and Litter Performance

The primary objective of this study was to determine the effects of supplemental dietary fat during lactation on sow BW, sow backfat thickness, sow feed consumption, litter size, and pig growth rate. Dietary treatments included 0, 3, 6, and 9% supplemental low acid yellow fat in a traditional corn-soybean meal basal lactation diet. A total of 160 Landrace and crossbred sows (approximately 40 per treatment) were included in the study. Sows fed 3 and 6% supplemental fat had greater (P<0.10) average backfat thickness at weaning. Sow weight change and feed consumption were inconsistent among dietary fat levels. Dietary fat level during lactation did not affect number of pigs born alive or number of stillborns. However, the 9% fat level was associated with more mummified pigs at birth. Number of pigs weaned was greater for the 0% supplemental fat than for the 9% fat level. The largest average pig weights at 21 (5.8±0.29 kg) and 28 (7.48±0.38) d of age were those from sows fed the 3% added fat diet. Sows with ≤25.4 mm backfat at farrowing had more pigs born alive (P<0.05), had less backfat at 21 and 28 d of lactation (P<0.05), and consumed more feed during wk 2 and 3 of lactation. Of all sows fed the control diet, sows with >25.4 mm backfat at farrowing consistently had heavier pigs throughout the lactation phase (P<0.05). Backfat loss during lactation was lower (P<0.05) for sows with ≤25.4 mm at farrowing within all dietary treatments. Consistent significant differences were not observed in sow weight loss or feed consumption between low and high backfat sows for each dietary treatment. Sow backfat loss during lactation is dependent on body condition at farrowing, in that, fatter sows at farrowing have greater backfat loss during lactation. Sows with ≤25.4 mm of backfat at farrowing responded to added dietary fat treatments and produced heavier pigs throughout the lactation period.     

Growth performance and carcass characteristics of pigs fed short-season corn hybrids

An experiment was conducted to determine growth performance, carcass characteristics, and fat quality of growing-finishing pigs fed diets based on short-season corn hybrids. Twenty-four individually housed, Cotswold, growing pigs with an initial BW of 41.4 (SD = 1.4) kg were blocked by BW and sex and randomly allotted from within block to 1 of 3 diets to give 8 replicate pigs per diet. Experimental diets consisted of a control based on barley and 2 diets based on corn as the main energy sources. A 3-phase feeding program for 20 to 50 kg (phase I), 50 to 80 kg (phase II), and 80 to 110 kg (phase III) of BW was used. Diets for each phase contained approximately 3.5 Mcal/kg of DE, with total lysine of 0.95, 0.75, and 0.64% in phase I, II, and III diets, respectively. Average daily gain, ADFI, and G:F were monitored weekly during each phase. Pigs were slaughtered after reaching a minimum BW of 100 kg to determine carcass characteristics. There were no effects of diet on ADG, ADFI, and G:F (0.45 +/- 0.02, 0.34 +/- 0.02, and 0.31 +/- 0.02 for phase I, II, and III, respectively). Carcass length, dressing percent, LM area, loin depth, backfat thickness, belly firmness, and L*, b*, and a* fat color were not different across dietary treatments. Pigs fed one corn variety had no differences in fatty acid profile with barley-fed pigs, whereas those fed the other variety of corn had a greater (P < 0.05) concentration of PUFA in their backfat. The results indicate that growth performance, carcass characteristics, and fat quality of pigs fed diets based on short-season corn hybrids and those fed the barley-based diet were not different.