Protective effects of scutellarin in experimental colitis in rats.

Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology for which effective treatments are lacking. Scutellarin is a flavonoid with anti-apoptotic, antioxidant and anti-inflammatory effects. We investigated the possible protective effects of scutellarin on UC induced by acetic acid in rats. We used five groups of male rats: control, scutellarin, UC, UC + scutellarin, UC + sulfasalazine. Colonic mucosal inflammation was evaluated microscopically. Malondialdehyde (MDA), superoxide dismutase (SOD) activity, total antioxidant status (TAS), nitric oxide (NO), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and DNA fragmentation levels were measured. Colon tissue sections were evaluated using immunohistochemistry for Bcl-2 and Bax, TUNEL staining and histopathology. Pretreatment with scutellarin significantly reduced histological damage. Scutellarin significantly reduced serum and tissue levels of MDA, NO, IL-6 and TNF-α, and increased enzymatic activity of SOD and TAS. Scutellarin suppressed apoptosis by down-regulation of Bax, reduction of DNA fragmentation and increased expression of Bcl-2. Apoptosis was increased, while antioxidant enzymes were significantly decreased; some histopathologic disorders also were seen in the UC group. Administration of scutellarin ameliorated the pathological and biochemical alterations caused by UC in rats. We found that scutellarin might be protective against UC by down-regulating pro-inflammatory cytokines and suppressing apoptosis and oxidative stress.

The protective effect of metformin in scopolamine-induced learning and memory impairment in rats.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease in the world. One of the most commonly prescribed oral antidiabetic drug, metformin, has been shown to have beneficial effects on restoring impaired cognitive function. In the present study, we investigated the effects of metformin on spatial memory in terms of alleviating scopolamine-induced learning and memory impairments in rats by using the Morris water maze (MWM) test and the modified elevated plus-maze (mEPM) test. Furthermore, we investigated the possible mechanisms of action of metformin in preventing cognitive dysfunction. METHODS: Male Wistar rats received metformin (50, 100, or 200 mg/kg/day) via gavage feeding for three weeks. Scopolamine was administered intraperitoneally before the probe step of the MWM test or the acquisition session of the mEPM test. RESULTS: The learning and memory impairment induced by scopolamine was reversed by metformin. In addition, metformin improved the level of phosphorylated AMP-activated protein kinase and cAMP responsive element binding protein. However, metformin pretreatment had no impact on inhibiting the scopolamine-induced changes in acetylcholine levels. Furthermore, metformin exerted its antioxidant effect by significantly reversing scopolamine-induced changes in malondialdehyde, total antioxidant status, and superoxide dismutase levels in the hippocampus. CONCLUSION: Our results indicate that one of the most commonly used antidiabetic drug, metformin, has the potential to prevent the development of dementia and be a novel therapeutic drug for the amelioration of cognitive dysfunction in AD.

Does protocatechuic acid, a natural antioxidant, reduce renal ischemia reperfusion injury in rats?

BACKGROUND: Protocatechuic acid (PCA), which has antioxidant property, is a simple phenolic compound commonly found in many plants, vegetables, and fruits, notably in green tea and almonds. Present study was an investigation of the effects of PCA on rat kidney with ischemia/reperfusion (IR) injury. METHODS: Sprague-Dawley rats were randomly divided into 4 groups: (1) Sham, (2) Renal IR, (3) Renal IR+Vehicle, and (4) Renal IR+PCA. Renal reperfusion injury was induced by clamping renal pedicle for 45 minutes after right nephrectomy was performed, followed by reperfusion for 3 hours. Dose of 80 mg/kg PCA was intraperitoneally administered to 1 group immediately before renal ischemia; 33% polyethylene glycol was used as vehicle. Total antioxidant status (TAS), malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor alpha (TNF-α), and interleukin-6 levels were measured in blood and kidney tissue samples taken from sacrificed rats. Kidney tissue samples were examined and scored histopathologically. Terminal deoxynucleotidyltransferase-mediated dUTP digoxigenin nick end labeling assay method was used to detect apoptotic cells. RESULTS: It was found that PCA significantly reduced serum MDA, TNF-α, and kidney MDA levels, while it increased serum and kidney TAS and SOD levels. Histopathological scores were significantly higher for the group given PCA. CONCLUSION: PCA reduced oxidative stress and can be used as an effective agent in treatment of renal IR injury.

Selenium Protects Retinal Cells from Cisplatin-Induced Alterations in Carbohydrate Residues.

BACKGROUND: Investigate alterations in the expression and localization of carbohydrate units in rat retinal cells exposed to cisplatin toxicity. AIMS: The aim of the study was to evaluate putative protective effects of selenium on retinal cells subjected to cisplatin. STUDY DESIGN: Animal experiment. METHODS: Eighteen healthy Wistar rats were divided into three equal groups: 1. Control, 2. Cisplatin and 3. Cisplatin+selenium groups. After anesthesia, the right eye of each rat was enucleated. RESULTS: Histochemically, retinal cells of control groups reacted with α-2,3-bound sialic acid-specific Maackia amurensis lectin (MAA) strongly, while cisplatin reduced the staining intensity for MAA. However, selenium administration alleviated the reducing effect of cisplatin on the binding sites for MAA in retinal cells. The staining intensity for N-acetylgalactosamine (GalNAc residues) specific Griffonia simplicifolia-1 (GSL-1) was relatively slight in control animals and cisplatin reduced this slight staining for GSL-1 further. Selenium administration mitigated the reducing effect of cisplatin on the binding sites for GSL-1. A diffuse staining for N-acetylglucosamine (GlcNAc) specific wheat germ agglutinin (WGA) was observed throughout the retina of the control animals. In particular, cells localized in the inner plexiform and photoreceptor layers are reacted strongly with WGA. Compared to the control animals, binding sites for WGA in the retina of rats given cisplatin were remarkably decreased. However, the retinal cells of rats given selenium reacted strongly with WGA. CONCLUSION: Cisplatin reduces α-2,3-bound sialic acid, GlcNAc and GalNAc residues in certain retinal cells. However, selenium alleviates the reducing effect of cisplatin on carbohydrate residues in retinal cells.

The effect of surgery (Ovariohysterectomy) on the plasma disposition of meloxicam following intravenous administration in dogs.

BACKGROUND: Meloxicam (MLX) is a nonsteroidal anti-inflammatory drug used in the relief of postoperative pain for human and veterinary medicine. This study was designed to investigate the effect of surgery on the plasma disposition of MLX in dogs undergoing ovariohysterectomy following a single intravenous injection at a dose of 0.2 mg/kg bodyweight. Eight crossbred bitches were used in the study. A two-phase experimental design with a 10-day washout period was used. Pre-operative MLX was administered intravenously to 8 bitches about 10 days before surgery (Phase I, control) at a dose of 0.2 mg/kg bodyweight and peri-operative MLX was administered intravenously after anaesthesia and 15 min before the start of surgery (Phase II). Blood samples were collected from all animals at various times between 1 and 96 h after the drug administrations in both phases. The drug concentrations were analysed using high performance liquid chromatography. RESULTS: The volume of plasma MLX distribution at steady-state (Vdss) of the control group (Vdss: 263.0 ml/kg) was significantly greater (P < 0.05) compared to that of the surgery group (Vdss: 149.3 ml/kg). The AUC values were higher (29.5 vs. 23.0 µg.h(2)/ml) and the CL values were lower (7.7 vs. 10.5 ml.h/kg) in the surgery group compared to the control group, respectively, but differences were not significant. CONCLUSIONS: The results of the present study indicated that surgery could alter the plasma disposition of MLX and thus the drug efficacy and side effects such as gastrointestinal ulceration, unusual bleeding and loss of kidney function/failure when repeated doses are used.

Plasma disposition, milk excretion and parasitological efficacy of mebendazole in donkeys naturally infected by Cyathostominae.

Mebendazole (MBZ) has been licensed for use in horses and donkeys, however there are no data available in the literature regarding its pharmacokinetic disposition and efficacy in donkeys. This study was designed to determine the plasma disposition, milk excretion and anthelmintic efficacy of MBZ in donkeys naturally infected by Cyathostominae. The animals were allocated to three groups, each of six donkeys. One group was untreated control (C-group) and the others were treated using a paste formulation of MBZ administered per os at the manufacturer's recommended horse dosage of 10 mg/kg body weight (MBZ 1) and at the double horse dosage 20 mg/kg body weight (MBZ 2). Blood and milk samples were collected at various times between 1h and 120 h post treatment and analyzed by high performance liquid chromatography with photodiode array detector. Individual FECs (Faecal Egg Counts) were performed on each animal before the treatment (day-3) and weekly from day 7 until day 56 post treatment using a modified McMaster technique. The plasma concentrations and systemic exposure of MBZ in donkeys were relatively lower compared with the other methylcarbamate benzimidazoles. Dose-dependent plasma dispositions of MBZ were observed at the increased dosage (10 mg/kg vs 20 mg/kg) in donkeys. MBZ was not detected in any milk samples at a dosage of 10 mg/kg. However, the parent drug reached 0.01 µg/ml peak milk concentration at 10.66 h and AUCmilk/AUCplasma value was 0.18 ± 0.02 at a dosage of 20 mg/kg bodyweight. This study indicated that per os administration of MBZ has a minimal disposition rate into the milk and may be used in lactating donkeys with zero milk-withdrawal period. The results of FECRT for both MBZ dosages were efficient (>95% efficacy) until day 28. This trial demonstrates that MBZ oral paste at horse dosage (10 mg/kg B.W.) was effective and safety for the treatment of Cyathostominae in donkeys. Therefore, similar dosage regimens of MBZ could be used for horses and donkeys.

Lycopene Ameliorates Experimental Colitis in Rats via Reducing Apoptosis and Oxidative Stress.

Inflammatory bowel disease (IBD) is an inflammatory disorder involving colitis. Lycopene is a naturally occurring carotenoid that has attracted considerable attention as a potential chemopreventive agent. The impact of lycopene on colitis is currently unknown. The aim of this study was to investigate the protective effects of lycopene in a rat model of colitis induced by acetic acid. The animals were randomly divided into the following five groups: the control group, colitis group, colitis + sulfasalazine group as a positive control group, colitis + lycopene and lycopene groups. Colonic mucosal injury was assessed by biochemical and histopathological examinations. Malondialdehyde (MDA), superoxide dismutase (SOD) activity, total antioxidant status (TAS), ceruloplasmin (CPN), total sialic acid and iron (Fe) levels were evaluated in blood samples. MDA, SOD, TAS and DNA fragmentation levels were also measured in colon tissues. MDA (p < 0.05), total sialic acid (p < 0.05) and DNA fragmentation levels (p < 0.01) were significantly higher, and the activity of the antioxidant enzyme were lower in the colitis group than in the control group. Treatments with lycopene in the colitis decreased MDA, total sialic acid and DNA fragmentation levels, while SOD activity (p < 0.05), TAS (in colon p < 0.05; in serum p < 0.01), CPN (p < 0.05) and Fe levels (p < 0.05) were significantly increased. The histopathological evaluation also confirmed the foregoing findings. Treatment with lycopene ameliorated the biochemical and pathological alterations caused by colitis. The results obtained in this study indicate that lycopene may exert protective effects in experimental colitis and might, therefore, be useful for treatment of IBD.

Comparative pharmacokinetics and bioavailability of albendazole sulfoxide in sheep and goats, and dose-dependent plasma disposition in goats.

BACKGROUND: The aims of this study were to compare the pharmacokinetics of albendazole sulfoxide (ABZ-SO, ricobendazole) in goats and sheep at a dose of 5 g/kg bodyweight (BW), after intravenous (IV) and subcutaneous (SC) administrations, and to investigate the effects of increased doses (10 and 15 mg/kg BW) on the plasma disposition of ABZ-SO in goats following SC administration. A total of 16 goats (Capra aegagrus hircus, eight males and eight females) and 8 sheep (Ovis aries, four males and four females) 12-16 months old and weighing 20-32 kg, were used. The study was designed according to two-phase crossover study protocol. In Phase-1, eight sheep were assigned as Group I and 16 goats were allocated into two groups (Group II and Group III). ABZ-SO was applied to Group I (sheep) and Group II (goats) animals subcutaneously, and to Group III (goats) animals intravenously, all at a dose rate of 5 mg/kg BW. In Phase-2, the sheep in the Group I received ABZ-SO intravenously in a dose of 5 mg/kg BW; the goats in Group II and Group III received ABZ-SO subcutaneously at a dose of 10 mg/kg and 15 mg/kg BW, respectively. Blood samples were collected from the jugular vein at different times between 1 and 120 h after drug administrations. The plasma concentrations of ABZ-SO and its metabolites were analysed by high performance liquid chromatography. RESULTS: In goats, the area under the curve, terminal half-life and plasma persistence of ABZ-SO were significantly smaller and shorter, respectively, compared with those observed in sheep following both IV and SC administrations at a dose of 5 mg/kg BW. On the other side, dose-dependent plasma dispositions of ABZ-SO were observed following SC administration at increased doses (10 and 15 mg/kg) in goats. CONCLUSIONS: Consequently, ABZ-SO might be used at higher doses to provide higher plasma concentration and thus to achieve greater efficacy against the target parasites.

Comparison of pre-treatment and post-treatment use of selenium in retinal ischemia reperfusion injury.

AIM: To investigate the effects of selenium in rat retinal ischemia reperfusion (IR) model and compare pre-treatment and post-treatment use. METHODS: Selenium pre-treatment group (n=8) was treated with intraperitoneal (i.p.) selenium 0.5 mg/kg for 7d and terminated 24h after the IR injury. Selenium post-treatment group (n=8) was treated with i.p. selenium 0.5 mg/kg for 7d after the IR injury with termination at the end of the 7d period. Sham group (n=8) received i.p. saline injections identical to the selenium volume for 7d with termination 24h after the IR injury. Control group (n=8) received no intervention. Main outcome measures were retina superoxide dismutase (SOD), glutathione (GSH), total antioxidant status (TAS), malondialdehyde (MDA), DNA fragmentation levels, and immunohistological apoptosis evaluation. RESULTS: Compared to the Sham group, selenium pre-treatment had a statistical difference in all parameters except SOD. Post-treatment selenium also resulted in statistical differences in all parameters except the MDA levels. When comparing selenium groups, the pre-treatment selenium group had a statistically higher success in reduction of markers of cell damage such as MDA and DNA fragmentation. In contrast, the post-selenium treatment group had resulted in statistically higher levels of GSH. Histologically both selenium groups succeeded to limit retinal thickening and apoptosis. Pre-treatment use was statistically more successful in decreasing apoptosis in ganglion cell layer compared to post-treatment use. CONCLUSION: Selenium was successful in retinal protection in IR injuries. Pre-treatment efficacy was superior in terms of prevention of tissue damage and apoptosis.

Protective effect of 2-APB on testicular ischemia-reperfusion injury in rats.

PURPOSE: We performed biochemical and histopathological evaluations to assess the effects of 2-APB on ischemia-reperfusion induced testicular damage. MATERIALS AND METHODS: A total of 28 rats were randomly divided into 4 groups, including sham treated, ischemia-reperfusion, ischemia-reperfusion plus 2 mg/kg 2-APB and ischemia-reperfusion plus 4 mg/kg 2-APB. Testicular tissue superoxide dismutase, glutathione, malondialdehyde, total antioxidant capacity and DNA fragmentation levels were determined. Testicular tissue samples were examined by histopathology and TUNEL staining. RESULTS: Mean superoxide dismutase, total antioxidant capacity and glutathione were significantly higher in the sham treated group than in the ischemia-perfusion group (p <0.05). Mean malondialdehyde and DNA fragmentation levels were significantly lower in the sham treated group than in the ischemia-reperfusion group (p <0.05). After 2-APB treatment superoxide dismutase, total antioxidant capacity and glutathione were significantly increased but malondialdehyde and DNA fragmentation levels were significantly decreased compared to the ischemia-reperfusion group (p <0.05). The number of TUNEL positive cells was significantly lower in the 2-APB treatment groups than in the ischemia-reperfusion group (p <0.05). CONCLUSIONS: In rats 2-APB reduced the oxidative stress and apoptosis caused by testicular ischemia-reperfusion injury. The testicular protective effect of 2-APB appears to be mediated through its antiapoptotic and antioxidative effects.

Comparative pharmacokinetics of levamisole-oxyclozanide combination in sheep and goats following per os administration.

Since there is no registered anthelmintic drug available for use in goats, extra-label use of drugs is a common practice in most countries. The aim of the present study was to compare the pharmacokinetic disposition of levamisole (LVM)-oxyclozanide (OXZ) combination in sheep and goats following per os administration. Goats (n = 8) and sheep (n = 8) 12- to 16-months-old were used for this study. The animals received tablet formulation of LVM and OXZ combination orally at a dose of 7.5 mg/kg and 15 mg/kg body weight, respectively. Blood samples were collected by jugular vein at different times between 5 min and 120 h after drug administrations. The plasma concentrations of LVM and OXZ were analyzed by HPLC following liquid-liquid phase extraction procedures. The plasma concentrations and systemic availabilities of both LVM and OXZ in goats were lower and the plasma persistence of LVM was shorter compared with those observed in sheep. Terminal half-lives (t1/2λz) of both molecules are shorter in goats compared with those in sheep. Goats treated with LVM-OXZ combination at the recommended dose for sheep may result in a reduced efficacy, because of under-dosing, which may increase the risk of drug resistance in parasites. Increased or repeated dose could be a strategy to provide higher plasma concentration and thus to improve the efficacy against the target parasites in goats compared with sheep. However, some adverse reactions may occur since LVM has relatively very narrow therapeutic index due to its nicotine-like structure and effect.

Étant donné qu'il n'y a aucun anthelminthique homologué disponible pour utilisation chez les chèvres, l'utilisation hors-homologation de médicaments est une pratique usuelle dans la plupart des pays. L'objectif de la présente étude était de comparer la disposition pharmacocinétique de la combinaison levamisole (LVM)-oxyclozanide (OXZ) chez les moutons et les chèvres suite à l'administration per os. Des chèvres (n = 8) et des moutons (n = 8) âgés de 12 à 16 mois furent utilisés pour cette étude. Les animaux ont reçu une combinaison de comprimés de LVM et d'OXZ à une dose de 7,5 mg/kg et 15 mg/kg de poids corporel, respectivement. Des échantillons sanguins furent prélevés par ponction de la veine jugulaire à différents temps entre 5 min et 120 h suite à l'administration des médicaments. Les concentrations plasmatiques de LVM et d'OXZ furent analysées par HPLC suite à des procédures d'extraction de phase liquide-liquide. Les concentrations plasmatiques et les disponibilités systémiques de LVM et OXZ chez les chèvres étaient plus basses et la persistance plasmatique de LVM de plus courte durée comparativement à celles observées chez les moutons. Les demi-vies terminales (t1/2λz) des deux molécules sont plus courtes chez les chèvres comparativement à celles chez les moutons. Le traitement de chèvres avec la combinaison LVM-OXZ au dosage recommandé pour les moutons pourrait résulter en une efficacité moindre, dû à un sous-dosage, ce qui pourrait augmenter le risque de résistance au médicament chez les parasites. Des doses augmentées ou répétées pourraient s'avérer une stratégie pour obtenir des concentrations plasmatiques plus élevées et ainsi améliorer l'efficacité contre les parasites ciblés chez les chèvres comparativement aux moutons. Toutefois, quelques réactions indésirables peuvent survenir étant donné que le LVM a déjà un index thérapeutique assez étroit associé à sa structure et son effet apparentés à la nicotine.(Traduit par Docteur Serge Messier).

Plasma pharmacokinetics, faecal excretion and efficacy of pyrantel pamoate paste and granule formulations following per os administration in donkeys naturally infected with intestinal strongylidae.

The plasma disposition, faecal excretion and efficacy of two formulations of pyrantel pamoate in donkeys were examined in a controlled trial. Three groups of seven donkeys received either no medication (control) or pyrantel paste or granule formulations at horse dosage of 20mg/kg B.W. (equals 6.94 mg/kg PYR base) of body weight. Heparinized blood and faecal samples were collected at various times between 1 and 144 h after treatment. The samples were analysed by high-performance liquid chromatography. The last detectable plasma concentration (tmax) of paste formulation was significantly earlier (36.00 h) compared with granule formulation (46.29 h). Although, there was no significant difference on terminal half lives (t1/2: 12.39 h vs. 14.86 h), tmax (14.86 h vs. 14.00) and MRT (24.80 h vs. 25.44 h) values; the Cmax (0.09 µg/ml) AUC (2.65 µgh/ml) values of paste formulation were significantly lower and smaller compared with those of granule formulation (0.21 µg/ml and 5.60 µgh/ml), respectively. The highest dry faecal concentrations were 710.46 µg/g and 537.21 µg/g and were determined at 48 h for both paste and granule formulation of PYR in donkeys, respectively. Pre-treatment EPG of 1104, 1061 and 1139 were observed for the control, PYR paste and PYR granule groups, respectively. Pre-treatment EPG were not significantly different (P>0.1) between groups. Post-treatment EPG for both PYR treatment groups were significantly different (P<0.001) from the control group until day 35. Following treatments the PYR formulations were efficient (>95% efficacy) until day 28. In all studied donkeys, coprocultures performed at day-3 revealed the presence of Cyathostomes, S. vulgaris. Faecal cultures performed on different days from C-group confirmed the presence of the same genera. Coprocultures from treated animals revealed the presence of few larvae of Cyathostomes.

The protective effect of selenium in cisplatin-related retinotoxicity.

PURPOSE: The aim of this study is to evaluate the retinal toxicity of cisplatin and neuroprotective effect of selenium in cisplatin-related retinal toxicity. METHODS: Eighteen adult Wistar-Albino rats were divided into three groups. Group 1 (n = 6) received intraperitoneal (i.p.) injection of 2.5 ml physiologic saline for three days, group 2 (n = 6) received i.p. 16 mg/kg cisplatin for three days and group 3 (n = 6) received i.p. 16 mg/kg cisplatin for three days and 1.5 mg/kg twice daily selenium via gavage five days prior to cisplatin injection and for three days concomitantly with cisplatin injections. The total retinal thickness, outer nuclear layer (ONL), inner nuclear layer (INL) and inner plexiform layer (IPL) thicknesses were measured in hematoxylin/eosin and apoptotic index (AI) of ganglion cell layer (GCL) and INL was evaluated in TdT-mediated dUTP-biotin nick end labeling (TUNEL)-stained retina sections. RESULTS: Selenium statistically succeeded to reduce total retinal thickness in cisplatin-toxicated retinas: from 210.17 ± 23.40 to 173.55 ± 20.43, ONL: 49.79 ± 5.32 to 41.87 ± 6.30, INL: 33.72 ± 7.93 to 25.06 ± 5.73 and IPL: 53.61 ± 8.63 to 45.61 ± 6.92 µm in hematoxylin/eosin-stained retina sections. The AI was also reduced in INL (30.10 ± 12.02 to 19.48 ± 12.99) and in GCL (37.59 ± 17.70 to 33.15 ± 13.78). However, statistical significance was present in only AI values of INL. CONCLUSIONS: Selenium limited edema due to the toxicity and reduced the retinal thickness and showed neuroprotection in cisplatin-induced retinotoxicity.

The effect of fasting on the plasma disposition of triclabendazole following oral administration in goats.

This study was designed to investigate the effect of feeding on the plasma disposition of triclabendazole (TCBZ) in goats following oral administration. A total of eight goats, aged 14-16 months and weighing 20-30 kg were used in this study. The animals were allocated into two groups (fasted and fed groups) of four animals each. The goats in fed group were fed ad libitum but the animals in fasted group were not fed 24 h before and 6 h after drug administration. Commercial oral drench formulation of TCBZ (Endex-K, 5%) was administered orally to animals in two groups at dose of 10mg/kg bodyweight. Heparinized blood samples were collected between 1 and 192 h after treatment and the plasma samples were analysed by high performance liquid chromatography (HPLC) for TCBZ, TCBZ sulphoxide (TCBZ-SO), and TCBZ sulphone (TCBZ-SO(2)). Relatively very low concentration of TCBZ parent drug was detected between 2 and 48 h, but TCBZ-SO and TCBZ-SO(2) metabolites were present between 2 and 192 h in the plasma samples of fed and fasted animals. Fasting significantly enhanced the plasma concentration of TCBZ and its metabolites. The availability of TCBZ, TCBZ-SO and TCBZ-SO(2) in the plasma samples of fasted goats were markedly greater compared to those of fed goats. It was concluded that fasting decreases the digesta flow rate and prolongs the retention of the drug into the gastrointestinal tract, resulting in enhanced quantitative gastrointestinal absorption or systemic availability of TCBZ and its metabolites in fasted goats.

Comparative plasma disposition, bioavailability and efficacy of ivermectin following oral and pour-on administrations in horses.

Pour-on formulations of endectocides decrease the risk of injury for both user and animal, and are particularly convenient for animal owners who can apply the product. This study was designed to investigate the plasma disposition and efficacy of ivermectin (IVM) following pour-on, per os and intravenous administrations. Eighteen female horses weighing 510-610 kg were used in this study. The animals were allocated into three groups (per os, pour-on and intravenous groups). The equine paste, bovine pour-on and bovine injectable formulations of IVM were administered orally, topically and intravenously at the dose rates of 0.2, 0.5 and 0.2mg/kg bodyweight, respectively. Heparinized blood samples and hair samples were collected at various times between 1h and 40 days. The samples were analysed by high performance liquid chromatography with fluorescence detector. Faecal strongyle egg counts (EPG) were performed by a modified McMaster's technique before and at weekly intervals during 10 weeks after treatment. The results indicated that the plasma concentration and systemic availability of IVM was lower but the plasma persistence was prolonged after pour-on administration compared with per os route. IVM (paste) reduced the EPG by >95% for 10 weeks, whereas the reduction in pour-on group varied from 82 to 97%. EPG reduction in pour-on group was lower than that of per os group. Degradation on the application site, cutaneous biotransformation, binding of IVM to the haircoat and/or sebum are probably responsible for the relatively lower bioavailability of IVM in horses after pour-on administration. In conclusion, the poor plasma availability observed after pour-on administration could result in subtherapeutic plasma concentrations, which may promote the development of drug resistance in parasites.

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 1h 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(1/2lambdaz) (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.

Sex-related plasma disposition of ivermectin following pour-on administration in goats.

The effect of sex difference on the pharmacokinetic profiles of ivermectin (IVM) was investigated following pour-on administration in goats. A total of 12 (six males and six females) Kilis goats were allocated into two treatment groups with respect to sex. The pour-on formulation of IVM was administered topically (pour-on) at dose rate of 0.5mg/kg bodyweight. Blood samples were collected at various times between 1h and 40 days after treatment and the plasma samples were analysed by high-performance liquid chromatography (HPLC) using fluorescence detection. Substantial sex-related differences on the plasma disposition of IVM were observed between males and female goats following pour-on administration. The last detectable plasma concentration of IVM was significantly later in males (16.17 days) compared with female animals (10.67 days). There were no significant differences on C(max), t(max) and the area under the concentration-time curve-AUC values between male and female groups, respectively. However the terminal half-life (t(1/2lambdaz)) and mean plasma residence time (MRT) in male goats (2.35 days and 4.78 days, respectively) were significantly longer compared with female animals (1.42 days and 3.55 days, respectively) and this suggesting that the excretion patterns of IVM in male and female animals are probably different each other.