Cengiz Gokbulut

Determination of the quality parameters of pike perch Sander lucioperca caught by gillnet, longline and harpoon in Turkey

The effects of the different catching methods (gillnet, longline, harpoon) on sensory, chemical (pH, total volatile base nitrogen, K-value) and microbiological (total viable count [TVC]) changes in pike perch Sander lucioperca stored in ice were investigated. The same soaking time was used for both gillnet and longline fishing. The catching method had considerable influence on the freshness quality of pike perch. The acceptable shelf life was 15 days for pike perch caught by gillnet, and 22 days for longline and harpoon. The initial concentrations of inosine monophosphate (2.4 μmol/g) in pike perch caught by gillnet were significantly lower (P<0.05) than longline (4.1 μmol/g). and especially by harpoon (16.7 μmol/g). However, the initial K-values for fish caught by harpoon were significantly (P<0.05) lower (24.36%) than fish caught by longline and gillnet (57.69%, 64.41%, respectively). The average K, Ki, G and H-values at rejection day in terms of sensory assessment were approximately 90, 98, 156 and 40%, respectively, for all catching methods during ice storage. However, TVC reached 7.0 log cfu/g after approximately 11 days of storage for fish caught by gillnet, 19 days for fish caught by longline and 8 days for fish caught by harpoon. The result of this study suggests that the best catching method for preserving the freshness of pike perch is longline, based on the data obtained from the sensory and microbiological analysis.

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 McMasters 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.

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.

Pharmacokinetics of danofloxacin following intravenous and intramuscular administration in donkeys

Danofloxacin (DNF) is a synthetic antibacterial agent of thefluoroquinolone group, developed specifically for use in veteri-nary medicine. The drug possesses good in vitro activity against avariety of pathogens, including gram-positive and gram-negativebacteria, mycoplasmas, and intracellular pathogens, such asBrucella and Chlamdia species; but it has poor activity againstanaerobes (Wolfson & Hooper, 1985; Neu, 1987; McKellar et al.,1998; Aliabadi et al., 2003a).Danofloxacin shares with other fluoroquinolones, such asenrofloxacin and ciprofloxacin, a wide spectrum of activity, alarge 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 fluoroquinol-ones 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 usedwidely in horses (Bertone et al., 2000; Carretero et al., 2002;Gardner et al., 2004). Pharmacokinetic disposition of DNF hasbeen evaluated in many animal species including cattle, goats,sheep, camels, rabbit, chickens, turkeys, pig and horses (Knollet al., 1999; McKellar et al., 1999; Lindecrona et al., 2000;Atef et al., 2001; Aliabadi et al., 2003a,b; Shojaee Aliabadi L Haritova et al., 2006; Fernandez-Varon et al.,2006, 2007).There is a paucity of data available on the pharmacokineticsof drugs used in donkeys including antibiotics, as donkeys areoften neglected species in domestic animals. Different classes ofdrugs used in horses and ruminants are commonly extrapo-lated to donkeys without optimization of dosing regimens anddetermination of pharmacokinetic and pharmacodynamicproperties. Because of the lack of registered drugs for donkeys,antimicrobials licensed for horses or ruminants are used fortreatment of bacterial infections in this species with same doserates. In the literature, data are available only on thepharmacokinetics of gentamicin, sulfamethoxazole with tri-methoprim and marbofloxacin in donkeys (Welfare et al.,1996; Peck et al., 2002; Gonza´lez et al., 2007). It has beenreported that donkeys have a greater capacity to metabolizecertain drugs compared with horses; thus higher dosage orshorter intervals are required for maintaining effective con-centrations (Welfare et al., 1996; Matthews et al., 1997Coakley et al., 1999; Peck et al., 2002). Therefore, the aimof the present study was to determine the pharmacokineticproperties of DNF in donkeys following intravenous (i.v.) andintramuscular (i.m.) administration at single dose of1.25 mg⁄kg bodyweight.Six native breed donkeys (Equus asinus) which ranged in agefrom 2 to 5 years and weighted 90–125 kg were used in thisstudy. The animals were kept indoors and had clover hay andwater available ad libitum throughout the course of the study.This study was approved by Animal Ethic Committee ofUniversity of Adnan Menderes. The animals were allocated intotwo groups of three such that the mean weight of animals ineach group was similar and the donkeys were identified byunique freeze brand or natural markings. Danofloxacin wasadministered according to a two-phase crossover design proto-col. In phase I, group I received i.v. the commercially availableinjectable 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 todrug 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 werecentrifuged at 5000 g for 20 min and plasma was transferred toplastic tubes. All the plasma samples were stored at )20 C untilthe determination of drug concentration. In addition, serumsamples were also collected to determine creatin kinase (CK)activity after i.m. administration. The samples were stored at4 C for 2 h until CK activity (expressed in U⁄L), which wasmeasured preinjection and after i.m. injection using a commer-cial available kit (CK EE547; Linear Chemicals , Barcelona,Spain).

The effect of sesame and sunflower oils on the plasma disposition of ivermectin in goats

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.

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.

Plasma disposition and milk excretion of eprinomectin following pour‐on administration in lactating donkeys

H. S. YALINKILINC* & V. VENEZIANO *Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Adnan Menderes, Aydin, Turkey; Veterinarian in practice, Potenza, Italy; DISCIZIA, Faculty of Veterinary Medicine, University of Naples Federico II, Naples, Italy; Department of Pathology and Animal Health, Faculty of Veterinary Medicine, University of Naples Federico II, Naples, Italy

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.

Plasma disposition, concentration in the hair, and anthelmintic efficacy of eprinomectin after topical administration in donkeys

OBJECTIVE To investigate plasma disposition, concentration in the hair, and anthelmintic efficacy of eprinomectin after topical administration in donkeys. ANIMALS 12 donkeys naturally infected with strongyle nematodes. PROCEDURES The pour-on formulation of eprinomectin approved for use in cattle was administered topically to donkeys at a dosage of 0.5 mg/kg. Heparinized blood samples and hair samples were collected at various times between 1 hour and 40 days after administration. Samples were analyzed via high-performance liquid chromatography with fluorescence detection. Fecal strongyle egg counts were performed by use of a modified McMaster technique before and at weekly intervals for 8 weeks after treatment. RESULTS Plasma concentration and systemic availability of eprinomectin were relatively higher in donkeys, compared with values reported for other animal species. Concerning the anthelmintic efficacy against strongyle nematodes, eprinomectin was completely effective (100%) on days 7 and 14 and highly effective (> 99%) until the end of the study at 56 days after treatment. No abnormal clinical signs or adverse reactions were observed for any donkeys after treatment. CONCLUSIONS AND CLINICAL RELEVANCE Eprinomectin had excellent safety. The relatively high plasma concentration after topical administration could result in use of eprinomectin for the control and treatment of parasitic diseases in donkeys.

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 manufacturers 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.