Copper is a trace element that accumulates in the body and forms harmful effects. Panax ginseng is a plant that possesses antioxidant properties. The purpose of this study is to evaluate whether Panax ginseng protects the livers of rats exposed to copper sulfate. The rats were randomly divided into four groups as control, Panax ginseng, copper sulfate and Panax ginseng + copper sulfate. At the end of the trial, blood and liver samples were obtained from the animals. Biochemical analysis was carried out in blood samples. Oxidant and antioxidant parameters were analyzed in liver samples. In addition, liver tissue sections were stained with the hematoxylin-eosin, Masson’s trichrome, periodic acid-Schiff, and rhodanine staining methods for histochemical and histopathological examinations. It was found that serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, also densities of copper and histopathological parameters except for central vein dilatation and malondialdehyde (MDA) value in the liver significantly increased in copper sulfate group compared to control group, but inflammatory cell infiltration and MDA value decreased in Panax ginseng + copper sulfate group compared to copper sulfate group. In addition, it was determined that glycogen density, glutathione (GSH) level and superoxide dismutase (SOD) activity in the liver significantly decreased in copper sulfate group compared to control group, and they increased in Panax ginseng + copper sulfate group compared to copper sulfate group. As a result, copper sulfate causes structural and oxidative abnormalities in the liver. Additionally, Panax ginseng helps to protect liver tissue by diminishing oxidative damage in copper sulfate toxicity.

Effects of stocking density (SD) and nano zinc on oxidative status, immune function, and DNA damage in broilers were examined in the current study. Totally 480 one-day-old male broilers (Ross 308) were randomly divided into 4 treatments each contained 8 replicates. A 2 ´ 2 factorial arrangement with two groups for dietary zinc (Zn) form (inorganic or nano) and two groups for SD (low = 12 birds/m2 and high = 18 birds/m2) was conducted. Basal diets based on the corn-soybean meal were formulated. Relative liver weight was lower (P<0.05) in broiler subjected high stocking density (HSD) but other lymphoid organ weights did not affect. Relative lymphoid organ weights were not affected by dietary nano zinc. HSD increased the serum corticosterone level of broiler (P<0.05) but did not affect the blood heterophil:lymphocyte ratio, serum glutathione, superoxide dismutase, and malondialdehyde levels. Dietary nano zinc had no effect on these stress indicators. Serum interferon-gamma, interleukin 12, and interleukin 18 levels were not affected by HSD. Dietary nano zinc tended to reduce the interferon-gamma level (P=0.05) but did not affect interleukin 12, and interleukin 18 levels in broiler. Eeither HSD or nano zinc had no effect on DNA damage in lymphocyte. In conclusion, HSD may decrease the relative lymphoid organ weights and increase the stress indicators but did not affect the immunity and DNA damage. Generally, dietary nano zinc had no effect on stress indicators, immunity, and DNA damage in broiler.

A trial was conducted to investigate the effect of dietary prebiotics supplementation on growth performance, relative carcass and organ weight, gut microbiome, and blood malondialdehyde (MDA) in broiler chickens subjected to delayed feed and water access post-hatch. A total of 648 one-d-old chicks (Ross 308) were randomly divided into 6 experimental groups, each consisting of 6 replicate pens having 18 chicks in each pen. The study followed a completely randomised design with 3x2 factorial arrangement of three levels of post-hatch restriction time (0, 24, and 48 h) and basal diets with or without mannan oligosaccharide (MOS) prebiotics supplementation (0 and 0.1% for starter and grower or 0 and 0.05% for finisher). The trial lasted for 42 days. The chicks were weighed at the end of restriction periods. Body weight gain (BWG), feed intake, and feed conversion ratio (FCR) were recorded for days 1 -21, 22-42, and 1-42. Relative carcass and organ weights were recorded on day 42 after slaughter. Gut microbe populations (mesophiles, coliforms, lactobacilli, and Enterobacteriaceae spp.) were enumerated on days 6 and 15 of the experiment. Blood MDA levels were measured at the end of the restriction period on days 15 and 42. There was no interaction between prebiotics and restriction on any mentioned parameters. Prebiotics had no effect on BWG, feed intake, FCR, relative yields of carcass and organs, gut microbial populations, or blood MDA levels. BWG of broilers subjected to 48 h restriction was lower (P < 0.05) for days 1-21 compared to those subjected to 0 and 24 h. Feed and water restriction for 48 h post-hatch increased the feed intake (on days 22-42 and 1-42) and FCR (at days 1 -21, 22-42, and 1-42) in comparison with those restricted for 0 and 24 h post-hatch (P < 0.01 and P < 0.001, respectively). There was no effect of restriction on relative carcass and organ yields, and blood MDA. On day 6 of the experiment the count of mesophiles was higher in broilers restricted for 48 h (P < 0.001) and coliforms and Enterobacteriaceae spp. counts were higher in broilers subjected to 24 h restriction compared to 0 or 48 h (P < 0.01 and P < 0.001, respectively). In conclusion, the use of prebiotics in broilers with post-hatch feed and water restriction did not influence growth performance, relative carcass and organ weight, gut microbe populations, and blood MDA level. However, post-hatch feed restriction for 48 h may negatively affect growth performance.

The duration and intensity of exercise are significant factors in oxidative, morphological, and functional changes of the gastrointestinal tract. This study aimed to investigate the effects of both exhaustive swimming and probiotic VSL#3 on rats that had been previously trained with moderate swimming. The rats were divided into four groups labeled: control (C), probiotic (P), exercise (E), and probiotic-exercise (PE). Groups P and PE were fed with probiotic mixture VSL#3. Groups E and PE had a 5-week moderate swimming program (1 h/day for 5 days/week), followed by a 1-week exhaustive swimming program (trained like in moderate program but 3 times with 150 min resting sessions, for 5 days/week). At the end of the program, the rats were euthanized. Malondialdehyde, superoxide dismutase, catalase, and reduced glutathione levels were measured in tissue samples from the gastrocnemius muscle, heart, liver, kidney, and colon. In vitro contractile activity and histomorphology of the colon were also determined. Exercise and/or probiotic decreased the oxidative stress and also increased the level of one or more of the antioxidant enzymes in some of the organs. Probiotics had more pronounced effects on colon morphology than exercise but unexpectedly this effect was non-trophic. In the colon, the thickness of the tunica muscularis and the number of goblet cells were not affected; however, probiotic administration decreased the crypt depth and tunica mucosa thickness. Exercise increased the Emax value of acetylcholine (ACh), while decreased its sensitivity. These findings suggest that exhaustive swimming does not cause oxidative stress and that probiotic consumption improves oxidative balance in trained rats. The probiotic intake does not alter the effect of exercise on the contractile activity of the colon. Colon mucosal changes induced by probiotics are independent of exercise.

INTRODUCTION:Cyclophosphamide (CP) is a potent anticancer agent; its clinical use is limited due to its marked cardiotoxicity. AIM:The present study was aimed at evaluating the cardioprotective effects of silymarin (SLY) and curcumin (CUR), which have strong antioxidant properties, against the toxic effects of high-dose CP on the heart of rats. MATERIALS AND METHODS:A total of 36 adult Wistar albino female rats were randomly divided into six groups. Group I (control group; nothing was administered), Group II (CP group; 30mg/kg/day CP was administered intraperitoneally to each animal for seven days), Group III (SLY group; 100mg/kg/day SLY by gavage for 14 days), Group IV (CUR group; 100mg/kg/day CUR by gavage for 14 days), Group V (SLY+CP group; 100mg/kg/day SLY by gavage for 14days plus 30mg/kg/day CP intraperitoneally starting from the seventh day) and Group VI (CUR+CP group; 100mg/kg/day CUR by gavage for 14days plus 30mg/kg/day CP intraperitoneally starting from the seventh day). Biochemical, histopathological and immunohistochemical methods were utilised for evaluation of the cardiotoxicity. RESULTS:The result showed that an increase in heart MDA and DNA fragmentation levels were detected while significant decreases were seen in SOD levels in CP alone group when compared to the other groups. CP caused severe damage in the histopathological status of heart tissue including intersititial oedema, haemorrhage, degeneration and necrosis in muscle fibrils and perinuclear vacuolization. A significant increase in the percentage of TUNEL-positive cells and γH2AX protein expression was detected in the CP-treated group compared to the control and other treated groups. There was significant increase in the percentage of caspase 3-positive cells and decrease in the percentage of Bcl-2 positive cells in the CP group compared to the control group and other treated groups. However, a significant decrease in the percentage of cTnI and cTnT immunoreactivity was also observed in the CP-treated group compared to the control and other treated groups. In the groups in which SLY and CUR were administered concurrently with CP, biochemical parameters, histopathological and immunohistochemical results were found to be significantly lower than in the CP-only group. CONCLUSIONS:These results lead to conclusion that the natural antioxidant SLY and CUR might have protective effects against CP-induced cardiotoxicity and oxidative stress in rats.

Abstract AIMS: To determine the plasma disposition of meloxicam in goats following S/C, oral or I/V administration at a single dose of 0.5 mg/kg bodyweight. METHODS: Five healthy Saanen goats, aged 12–14 months and weighing 35–40 kg, were used for a three phase cross-over design with a 10-day washout period, with meloxicam administered I/V, then orally and S/C. Heparinised blood samples (5 mL) were collected from all animals prior to drug administration (0 hours) and subsequently up to 96 hours. Concentrations of meloxicam in plasma were measured using high performance liquid chromatography. Concentration-time curves were fitted and pharmacokinetic parameters were estimated for each administration group. RESULTS: Subcutaneous administration of meloxicam exhibited unique plasma distribution characteristics that differed from oral and I/V administration. Mean peak plasma concentrations were greater (1.91 (SD 0.39) vs. 0.71 (SD 0.17) µg/mL) and the time to reach them shorter (3.20 (SD 1.64) vs. 14.33 (SD 2.19) hours) following S/C compared with oral administration (p<0.05). The terminal half-life was longer (15.16 (SD 4.74) vs. 10.69 (SD 1.49) hours) and the MRT was shorter (15.67 (SD 2.37) vs. 24.33 (SD 3.12) hours) following S/C than oral administration (p<0.05), but bioavailability was similar (98.24 (SD 9.62) vs. 96.49 (SD 10.71)%). CONCLUSION AND CLINICAL RELEVANCE: Subcutaneous administration of meloxicam resulted in long-term presence of drug at high concentration in goat plasma. This unique plasma disposition characteristic may offer an advantage in some clinical cases towards potentially improving the treatment efficacy in goats.

A trial was conducted to investigate the effects of a dietary organic acid blend for a period of 35 days on the growth performance, intestinal histomorphology and microflora of male broiler chicks with delayed access to feed. One hundred and ninety two one day old broiler chicks (ROSS 308) were randomly distributed into 4 groups housed in four replicate pens with 12 birds in each. A 2 × 2 factorial design was implemented. Four experimental groups were formed by two levels of dietary organic acid blend supplementation (Control and Fysal Dry®) and two periods of delayed feed access (0 and 36 h). At 36 h after hatching body weight and body weight change of chicks were significantly (P < 0.001) lower than groups fed immediately after hatching. Delayed feed access had an adverse impact (P < 0.001) on the body weight and feed consumption of broiler chickens on days 14 and 28. Between the days 28 and 35 of the feeding period, these differences disappeared. The relative weight of gizzard (P < 0.05), pancreas (P < 0.01) on day 6 and intestine (P < 0.05) on day 10, and gizzard (P < 0.01) on day 10 were reduced in birds subjected to delayed feed access. Dietary organic acid blend inclusion increased villus length (P < 0.001), whereas delayed feed access decreased villus length (P < 0.05) and increased the incidence of epithelial degeneration and basal membrane separation of the propria mucosa of villus in the jejenum. A significant decrease in Enterobacteriaceae count (P < 0.01) was noted in organic acid blend supplemented groups on day 25. Pectoral muscle malondialdehyde levels were decreased (P < 0.01) with dietary organic acid blend supplementation at day 10. Delayed feed access significantly increased (P < 0.05) the heterophil:lymphocyte ratio at day 6. Overall, dietary organic acid blend supplementation helped broiler chicks to develop a healthier intestinal microflora and this may, in turn, inhibit the delayed feed access-induced increase in malondialdehyde in the early growing period. However, the inclusion of organic acid blend to broiler diets may not be a protective management practice in preventing delayed feed access-related growth depression of broiler chickens.

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Adnan Menderes University, Aydin, Turkey; Department ofParasitology, Faculty of Veterinary Medicine, Adnan Menderes University, Aydin, Turkey; Department of Animal Nutrition and NutritionDiseases, Faculty of Veterinary Medicine, Adnan Menderes University, Aydin, Turkey

Danofloxacin (DNF) is a synthetic antibacterial agent of the fluoroquinolone group, developed specifically for use in veterinary medicine. The drug possesses good in vitro activity against a variety of pathogens, including gram-positive and gram-negative bacteria, mycoplasmas, and intracellular pathogens, such as Brucella and Chlamdia species; but it has poor activity against anaerobes (Wolfson & Hooper, 1985; Neu, 1987; McKellar et al., 1998; Aliabadi et al., 2003a). Danofloxacin shares with other fluoroquinolones, such as enrofloxacin and ciprofloxacin, a wide spectrum of activity, a large volume of distribution and activity at low concentrations (Van Cutsem et al., 1990; Spreng et al., 1995; Brown et al., 1996). Pharmacokinetic properties of different fluoroquinolones have been extensively studied on several animal species (Knoll et al., 1999; Atef et al., 2001; Fernandez-Varon et al., 2006). In addition, some fluoroquinolones, such as DNF, moxifloxacin, marbofloxacin and enrofloxacin, are being used widely in horses (Bertone et al., 2000; Carretero et al., 2002; Gardner et al., 2004). Pharmacokinetic disposition of DNF has been evaluated in many animal species including cattle, goats, sheep, camels, rabbit, chickens, turkeys, pig and horses (Knoll et al., 1999; McKellar et al., 1999; Lindecrona et al., 2000; Atef et al., 2001; Aliabadi et al., 2003a,b; Shojaee Aliabadi & Lees, 2003; Haritova et al., 2006; Fernandez-Varon et al., 2006, 2007). There is a paucity of data available on the pharmacokinetics of drugs used in donkeys including antibiotics, as donkeys are often neglected species in domestic animals. Different classes of drugs used in horses and ruminants are commonly extrapolated to donkeys without optimization of dosing regimens and determination of pharmacokinetic and pharmacodynamic properties. Because of the lack of registered drugs for donkeys, antimicrobials licensed for horses or ruminants are used for treatment of bacterial infections in this species with same dose rates. In the literature, data are available only on the pharmacokinetics of gentamicin, sulfamethoxazole with trimethoprim and marbofloxacin in donkeys (Welfare et al., 1996; Peck et al., 2002; González et al., 2007). It has been reported that donkeys have a greater capacity to metabolize certain drugs compared with horses; thus higher dosage or shorter intervals are required for maintaining effective concentrations (Welfare et al., 1996; Matthews et al., 1997Coakley et al., 1999; Peck et al., 2002). Therefore, the aim of the present study was to determine the pharmacokinetic properties of DNF in donkeys following intravenous (i.v.) and intramuscular (i.m.) administration at single dose of 1.25 mg/kg bodyweight. Six native breed donkeys (Equus asinus) which ranged in age from 2 to 5 years and weighted 90–125 kg were used in this study. The animals were kept indoors and had clover hay and water available ad libitum throughout the course of the study. This study was approved by Animal Ethic Committee of University of Adnan Menderes. The animals were allocated into two groups of three such that the mean weight of animals in each group was similar and the donkeys were identified by unique freeze brand or natural markings. Danofloxacin was administered according to a two-phase crossover design protocol. In phase I, group I received i.v. the commercially available injectable solution of DNF (Advocin®, 2.5% w/v, Pfizer, Turkey) at a dose of 1.25 mg/kg bodyweight and group II received i.m. the same formulation at the same dose rate into gluteal muscle. A 2-week washout period was allowed between the two phases. Heparinized blood samples (5 mL) were collected 1 h prior to drug administration and 5, 15, 30, 45 min and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 36 and 48 h post-treatment. Blood samples were centrifuged at 5000 g for 20 min and plasma was transferred to plastic tubes. All the plasma samples were stored at −20 °C until the determination of drug concentration. In addition, serum samples were also collected to determine creatin kinase (CK) activity after i.m. administration. The samples were stored at 4 °C for 2 h until CK activity (expressed in U/L), which was measured preinjection and after i.m. injection using a commercial available kit (CK EE547; Linear Chemicals®, Barcelona, Spain). The parent compound of DNF in plasma was analysed using validated high-performance liquid chromatography (HPLC) following a liquid–liquid phase extraction procedure with a minor modification of the methods described by (Garcia et al., 2000). The mobile phase was a mixture of acetonitrile–water to which triflouroacetic acid was added (0.1% v/v) and delivered (Agilent 1100 Series QuatPump; Waldbronn, Germany) isocratically at a flow rate of 1 mL/min. A Nemesis nucleosil C18 column (4 μ, 150 × 4.6 mm) (Phenomenex, Cheshire, UK) with nucleosil C18 guard column (Phenomenex) was used for the analysis. The column was maintained at 40 °C throughout the analysis in a column oven. The eluate was continuously monitored using fluorescence detection for DNF (Agilent 1100 Series; Waldbronn, Germany) (λex 280 nm and λem 440 nm). The analytical method used for DNF in donkey plasma was validated prior to the start of the studies. Recoveries of the two molecules under study were measured by comparison of the peak areas from spiked plasma samples with the areas resulting from direct injections of standards. The inter-assay precision of the extraction and chromatography procedures was evaluated by processing replicate aliquots of drug-free donkey plasma samples containing known amounts of the drugs on different days. Calibration graph for DNF was prepared (linear range 0.01–10 μg/mL). The slope of the lines between peak areas and drug concentration was determined by least squares linear regression and showed correlation coefficients between 0.997 and 0.999. The limit of quantification (LOQ) was 0.01 μg/mL for plasma analysis. This value being the lowest concentrations detected with a coefficient of variations (CV) lower than 20%. The assay validation of DNF indicated a percentage of recovery of 93.71% (n = 36), intra-assay variation (CV) of 7.49 (n = 16), inter-assay CV of 6.86 (n = 20). The plasma concentration vs. time curves determined after each treatment (i.v. and i.m.) in individual animals were semi-logarithmically fitted with winnonlin software program (Version 4.1; Pharsight Corporation, Mountain View, CA, USA). Pharmacokinetic parameters for each animal were analysed using noncompartmental model analysis for both i.v. and i.m administrations (Gibaldi & Perrier, 1982). The pharmacokinetic parameters are reported as mean ± SD. Mean pharmacokinetic parameters after i.v. and i.m. administration were statistically compared using Student’s t-test. Mean parameters were considered significantly different at P < 0.05. No adverse response was observed for any of the treatments during the study. Semi-logarithmic plot of mean plasma concentration vs. time curves for DNF following i.v. and i.m. dose of 1.25 mg/kg bodyweight are shown in Fig. 1. The pharmacokinetic data associated with each route of drug administrations are given in Table 1. Danofloxacin had a large volume of distribution (Vdss) of 5.95 ± 1.00 L/kg, an elimination half-life (t1/2λz) of 7.25 ± 0.91 h and a clearance (Cl) of 1.00 ± 0.17 L·h/kg after i.v. administration. Following i.m. administration it was well adsorbed with an absolute bioavailability (F) of 100.54 ± 8.91% and a mean absorption time (MAT) of 3.12 ± 1.54 h, and achieved quickly a maximum plasma concentration (Cmax) of 0.15 ± 0.05 μg/mL at 0.88 ± 0.41 h. The mean residence time (MRT) observed after i.m. administration (9.10 h) is significantly longer compared with the value observed after i.v. route (5.98 h). Mean (±SD) plasma concentration profiles of danofloxacin following intravenous and intramuscular administration (1.25 mg/kg) to donkeys (n = 6). Serum CK activity at first 8 h after i.m. administration increased nine-fold compared with preinjection levels (Fig. 2). Danofloxacin was absorbed rapidly from the i.m. injection site and reached the peak of plasma concentration at 0.88 h in donkeys. Similar results were reported for cattle (Giles et al., 1991a), sheep (McKellar et al., 1998) and goats (Atef et al., 2001). Moreover significantly longer t1/2λz and MRT were observed following i.m. route compared with after i.v. administration in the present study. Mean (±SD) serum creatine kinase activity (U/L) after intramuscular administration of danofloxacin (1.25 mg/kg) to donkeys (n = 6). It is widely known that horses exhibit poor tolerability to irritant drugs when injected i.m. Kaartinen et al. (1997) reported that tissue reactions (e.g. swelling and tenderness) to enrofloxacin, and serum CK activity increased 10-fold. In another studies, CK activity was increased three-fold (12 h) for danofloxacin (Fernandez-Varon et al., 2006) after i.m. administration in horses. In this study, CK activity increased up to nine-fold (8 h) compared with preinjection levels. The systemic bioavailability (100.54%) of DNF after i.m. was almost complete in donkeys and higher than horses with 88% bioavailability (Fernandez-Varon et al., 2006). This reflects that tissue irritation does not appear to affect bioavailability of DNF in donkeys after i.m. administration. The plasma pharmacokinetic parameters determined following i.v. and i.m. administration of DNF to donkeys are not similar to those reported for horses at same dosage (Fernandez-Varon et al., 2006). Danafloxacin was more rapidly cleared in donkeys (1.00 L/h/kg) compared with horses (Cl: 0.34 L/h/kg) and following i.m. administration DNF reached a lower Cmax in donkeys (0.15 μg/mL) than in horses (0.35 μg/mL). Moreover, DNF displayed almost three times larger volume of distribution in donkeys (5.95 L/kg) compared with horses (2.00 L/kg) at same dosage. Although, the area under the concentration time curves (AUCs) of DNF after i.v. and i.m. administration were similar in donkeys (1.30 and 1.28 μg·h/mL, respectively), these values were almost three times smaller than those observed in horses after i.v. (3.80 μg·h/mL) and i.m. (3.32 μg·h/mL) administration (Fernandez-Varon et al., 2006). It has been suggested that serum concentrations related to the minimal inhibitory concentration (MIC) values are the best indicator of response to infections (Nix et al., 1991). PK/PD relationships between AUC from zero to 24 h and MIC, Cmax and MIC and time during which plasma concentrations exceed the MIC have been particularly useful in optimizing efficacy (McKellar et al., 2004). Although MIC values of DNF against equine pathogens are unknown, the serum concentrations of DNF exceeded MIC of 0.06 μg/mL against respiratory pathogens in cattle (Giles et al., 1991b; McKellar et al., 1998, 1999). Danofloxacin has a concentration dependent activity (McKellar et al., 2004); therefore, it is desirable to achieve a high Cmax after a single dose. Considering the plasma concentration in horses, higher loading doses of DNF may require in donkeys to provide effective plasma concentrations.

The effect of sesame oil (SSO) and sunflower oil (SFO) (the excipients) on the plasma disposition of ivermectin (IVM) following intravenous (i.v.) and subcutaneous (s.c.) administration at a dosage of 200 microg/kg was investigated in goats. Ten clinically healthy crossbred goats were used in the study. The animals were allocated by weight and sex into two groups of five animals each. Group 1 (n = 5) received the drug and excipient by the i.v. route only and group 2 received drug and excipient by the s.c. route only. The study was designed according to a two-phase crossover design protocol. In the first phase three animals in group 1 were i.v. administered IVM (0.2 mg/kg) + SSO (1 mL) and the other two animals received IVM (0.2 mg/kg) + SFO (1 mL). In the second phase animals were crossed over and received the alternate excipient with IVM at the same dosages. In group 2 during the first phase, three animals were s.c. administered IVM (0.2 mg/kg) + SSO (1 mL) and the other two animals were received IVM (0.2 mg/kg) + SFO (1 mL). In the second phase animals were crossed over and received the alternate excipient with IVM at the same dosages. A 4-week washout period was allowed between the two phases. In group 2 significantly increased dermal thickness was observed at the s.c. injection site of the all animals which received IVM during phase I regardless of the excipient. There was almost no change observed at the injection site of any animal during the second phase of the study following s.c. administration. In group 2 the plasma concentrations of IVM in the second phase for both excipient combinations were much higher than the plasma concentrations following first administration and appeared to be related with the dermal changes. The mean plasma disposition of IVM in combination with SSO or SFO was similar following i.v. administration. Longer terminal elimination half-lives and resultant longer mean resident time were observed after s.c. administration of the both combinations compared with i.v. administration.

Journal of Veterinary Pharmacology and TherapeuticsVolume 30, Issue 5 p. 489-491 Comparison of plasma pharmacokinetic profile of ivermectin following administration of subcutaneous injection (Baymec®) and oral tablet (Efektin®) in goats C. GOKBULUT, C. GOKBULUT Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Adnan Menderes, Isikli Koyu, Aydin, Turkey Research and Development Laboratory, University of Adnan Menderes, Aydin, TurkeySearch for more papers by this authorU. KARADEMIR, U. KARADEMIR Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Adnan Menderes, Isikli Koyu, Aydin, TurkeySearch for more papers by this authorM. BOYACIOGLU, M. BOYACIOGLU Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Adnan Menderes, Isikli Koyu, Aydin, TurkeySearch for more papers by this author C. GOKBULUT, C. GOKBULUT Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Adnan Menderes, Isikli Koyu, Aydin, Turkey Research and Development Laboratory, University of Adnan Menderes, Aydin, TurkeySearch for more papers by this authorU. KARADEMIR, U. KARADEMIR Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Adnan Menderes, Isikli Koyu, Aydin, TurkeySearch for more papers by this authorM. BOYACIOGLU, M. BOYACIOGLU Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Adnan Menderes, Isikli Koyu, Aydin, TurkeySearch for more papers by this author First published: 10 August 2007 https://doi.org/10.1111/j.1365-2885.2007.00888.xCitations: 13 Dr Cengiz Gokbulut, Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Adnan Menderes, Isikli Koyu, Aydin, Turkey. E-mail: [email protected] Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume30, Issue5October 2007Pages 489-491 RelatedInformation

This study evaluates the comparative plasma dispositions of ivermectin (IVM) and doramectin (DRM) following oral and subcutaneous administration (200 microg/kg) over a 40-day period in dogs. Twenty bitches were allocated by weight in to four groups (Groups I-IV) of five animals each. Animals in the first two groups (Groups I and II) received orally the injectable solutions of IVM and DRM, respectively, at the dose of 200 microg/kg bodyweight. The other two groups (Groups III and IV) received subcutaneously injectable solutions at the same dose rate. Blood samples were collected 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 IVM produced a significantly higher maximum plasma concentration (C(max): 116.80+/-10.79 ng/ml) with slower absorption (t(max): 0.23+/-0.09 day) and larger area under the concentration versus time curve (AUC: 236.79+/-41.45 ng day/ml) as compared with DRM (C(max): 86.47+/-19.80 ng/ml, t(max): 0.12+/-0.05 day, AUC: 183.48+/-13.17 ng day/ml) following oral administration of both drugs; whereas no significant differences were observed on the pharmacokinetic parameters between IVM and DRM after subcutaneous administrations. In addition, subcutaneously given IVM and DRM presented a significantly lower maximum plasma concentration (C(max): 66.80+/-9.67 ng/ml and 54.78+/-11.99 ng/ml, respectively) with slower absorption (t(max): 1.40+/-1.00 day and 1.70+/-0.76 day, respectively) and larger area under the concentration versus time curve (AUC: 349.18+/-47.79 ng day/ml and 292.10+/-78.76 ng day/ml, respectively) as compared with the oral administration of IVM and DRM, respectively. No difference was observed for the terminal half-lives ((t(1/2lambda(z)) and mean residence times (MRT) of both molecules. Considering the pharmacokinetic parameters, IVM and DRM could be used by the oral or subcutaneous route for the control of parasitic infection in dogs.

Ivermectin (IVM- Eqvalan® paste, 1.87%) and doramectin (DRM-Dectomax® 1%) were each administered orally to donkeys at 200μgkg−1 bodyweight. Blood and faecal samples were collected at predetermined times over 30days and plasma pharmacokinetics and faecal excretion determined. Maximum plasma concentrations (Cmax) of IVM (23.6ngml−1) and DRM (33.9ngml−1) were obtained at (tmax) 19.2 and 24h, respectively. The area under the concentration curve (AUC) of DRM (228.9ngdayml−1) was significantly larger than that of IVM (119.3ngdayml−1) and mean residence time (MRT) was 6.5 days for IVM and 9.1days for DRM. The highest (dry weight) faecal concentrations (9.33μgg−1 – IVM, 12.12μgg−1 – DRM) were detected at 55.9 and 48.0h, respectively and each compound was detected (⩾0.05μgg−1) in faeces between 11h and 9days following oral administration in donkeys.