The impact of nano/micro-plastics toxicity on seafood quality and human health: facts and gaps.

Contamination of the food and especially marine environment with nano/micro-plastic particles has raised serious concern in recent years. Environmental pollution and the resulting seafood contamination with microplastic (MP) pose a potential threat to consumers. The absorption rate of the MP by fish is generally considered low, although the bioavailability depends on the physical and chemical properties of the consumed MP. The available safety studies are inconclusive, although there is an indication that prolonged exposure to high levels of orally administered MP can be hazardous for consumers. This review details novel findings about the occurrence of MP, along with its physical and chemical properties, in the marine environment and seafood. The effect of processing on the content of MP in the final product is also reviewed. Additionally, recent findings regarding the impact of exposure of MP on human health are discussed. Finally, gaps in current knowledge are underlined, and the possibilities for future research are indicated in the review. There is an urgent need for further research on the absorption and bioavailability of consumed MP and in vivo studies on chronic exposure. Policymakers should also consider the implementation of novel legislation related to MP presence in food.

An Updated Review of Tetrodotoxin and Its Peculiarities.

Tetrodotoxin (TTX) is a crystalline, weakly basic, colorless organic substance and is one of the most potent marine toxins known. Although TTX was first isolated from pufferfish, it has been found in numerous other marine organisms and a few terrestrial species. Moreover, tetrodotoxication is still an important health problem today, as TTX has no known antidote. TTX poisonings were most commonly reported from Japan, Thailand, and China, but today the risk of TTX poisoning is spreading around the world. Recent studies have shown that TTX-containing fish are being found in other regions of the Pacific and in the Indian Ocean, as well as the Mediterranean Sea. This review aims to summarize pertinent information available to date on the structure, origin, distribution, mechanism of action of TTX and analytical methods used for the detection of TTX, as well as on TTX-containing organisms, symptoms of TTX poisoning, and incidence worldwide.

In vivo exposure of Albendazole sulphoxide by Haemonchus contortus and correlation between plasma and target tissue or gastrointestinal content dispositions in goats.

Sheep and goats are sharing different helminth parasites including Haemonchus contortus. Control of these helminths is based mainly on the use of anthelmintics. However, in goats, the application of anthelmintics is often carried out mainly at dosages determined for sheep without knowing the real effects and metabolism features. One of the several anthelmintic classes used against these parasites is (pro) benzimidazoles which are still widely in use in small ruminants in many countries. The objective of this study was to determine (i) the correlation between plasma and tissue or gastrointestinal content dispositions of ricobendazole (RBZ) in goats and (ii) the in vivo exposure of ricobendazole by H. contortus. Ten goats were experimentally infected with 10,000 larvae of H. contortus. Four weeks of post-infection, the animals received RBZ subcutaneously at 5 mg/kg body weight. Two goats were sacrificed per time at 1, 2, 4, 6 and 12 h after drug administration and, blood, bile, urine, liver, lung, muscle and kidney gastrointestinal tissues/fluids were collected. Adult H. contortus were collected from abomasum, and all samples were analysed by HPLC system. Ricobendazole (RBZ) and its sulphone metabolite were extensively excreted by urine and distributed to all tissues and digestive tract, mainly into the abomasum fluid. RBZ concentration in the lung and ABZSO2 in the kidney were relatively higher than those of other tissues, respectively. The parent drug and its metabolite were recovered in both male and female H. contortus. This study indicates that in goats the plasma concentration profiles of RBZ are strongly correlated with those achieved in different target tissues or fluids, which in turn, reflect the amount of drug taken up by parasites.

The residue levels of spinosad and abamectin in eggs and tissues of laying hens following spray application.

Spinosad (SPN) and abamectin (ABM) are used in poultry premises to control external parasites including red mites (Dermanyssus gallinae). This study aimed to determine levels of SPN (spinosyn A + spinosyn D) and ABM residues in egg and edible tissues of laying hens following spray application. A total of 36 laying hens were divided into four groups of nine birds each, and they were kept in individual cages. Two different concentrations of SPN (2 and 4 g/l) and ABM (0.025 and 0.033 g/l) were applied in stocked and empty cages, respectively. Eggs were collected individually for 30 days. All hens were sacrificed at day 30 post-treatment, and tissue samples (liver, breast muscle, fat and skin) were collected. The residue levels in eggs and tissues were determined by high pressure liquid chromatography. ABM residues were not detectable in egg samples. SPN residues in eggs and residues of both ABM and SPN in liver, muscle and fat were under the maximum residue limits (MRLs) following low and high concentration applications. However, although the MRLs have not been established for SPN and ABM in skin tissue of chicken, residues in the skin detected at the low and high concentrations were greater than the MRLs for other edible tissues (except fat tissue) indicating that a withdrawal period would be necessary for the skin tissue after ABM and SPN use in laying hens.

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.

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.

The effect of intravenous lipid emulsion (ILE) on the pharmacokinetic/toxicokinetic dispositions of ivermectin and carprofen in rabbits.

Intravenous lipid emulsion (ILE) has been widely used as an effective antidote in both veterinary and human medicine for the treatment of acute intoxications caused by drugs and pesticides with high lipid solubility. This study was conducted to investigate the effect of ILE co-administration on the kinetic dispositions of ivermectin (IVM) and carprofen (CRP) following intravenous bolus administration at subtoxic doses in rabbits.Twenty-four male New Zealand rabbits weighing 2.78 ± 0.2 kg were used in this study. Rabbits were divided into four groups (Group 1: IVM and Group 2: IVM + ILE or Group 3: CRP and Group 4: CRP + ILE), each group consisting of 6 animals. In the IVM study, Group 1 received IVM (0.6 mg/kg) alone while Group 2 received IVM (0.6 mg/kg) and ILE (2.5 ml/kg). In the CRP study, Group 3 received CRP (12 mg/kg) alone while Group 4 received CRP (12 mg/kg) and ILE (2.5 ml/kg). In both drug groups, ILE was administered 3 times as an i.v. bolus at the 10th min and repeated 4th and 8th h after the drug administration. Blood samples were collected from the auricular vein at various times after drug administration. The drug concentrations in plasma samples were determined by high-pressure liquid chromatography. Kinetic parameters were calculated using a non-compartmental model for both CRP and IVM.The C0 and area under the concentration-time curve from zero up to ∞ (AUC0-∞) values were significantly greater with ILE co-administration (2136 ng/ml and 360.84 ng.d/ml) compared to the IVM alone (1340.63 ng/ml and 206 ng.d/ml), respectively. Moreover, the volume of distribution (Vdss) and clearance (Cl) of IVM were reduced by approximately 42% and 46% with ILE co-administration compared to IVM alone resulting in a reduction of the distribution and slower elimination, respectively. Similar differences in C0, and Vdss values were also observed in CRP with ILE co-administration compared to CRP alone. ILE co-administration changed significantly the kinetic profile of both IVM and CRP in rabbits, supporting the lipid sink theory in which highly lipid-soluble compounds are absorbed into the lipid phase of plasma from peripheral organs such as the heart and brain affected by the acute toxicity of the compounds.

Plasma disposition and faecal excretion of eprinomectin following subcutaneous administration in Saanen and Alpine goats.

Eprinomectin is extensively used in veterinary medicine, particularly in the treatment of internal and external parasites in livestock, including goats. The pharmacokinetic behavior of eprinomectin in plasma and faeces was studied after a single subcutaneous administration in two different goat breeds at a dose of 0.2 mg/kg body weight. The study was conducted on one-year-old female Saanen (n = 8) and Alpine (n = 8) goats in a parallel design. There were no significant differences between Saanen and Alpine goats on the peak plasma concentration (Cmax, 28.59 ± 7.46 ng/mL vs. 37.69 ± 14.89 ng/mL), area under the curve (AUC0-∞, 93.08 ± 11.66 ng.d/mL vs. 116.98 ± 48.36 ng.d/mL), area under the first moment curve (AUMC0-∞, 311.05 ± 67.23 ng.d2/mL vs. 348.25 ± 202.64 ng.d2/mL) and mean residence time (MRT, 3.24 ± 0.77 d vs. 2.74 ± 0.64 d) values. The plasma terminal half-life and the time to reach peak plasma concentration were significantly higher in Saanen goats (T1/2λz, 2.18 ± 0.43 d; Tmax, 1.21 ± 0.25 d) than in Alpine goats (T1/2λz, 1.66 ± 0.41 d; Tmax, 0.79 ± 0.25 d). The results revealed that the plasma concentration of eprinomectin did not differ depending on the breed in Saanen and Alpine goats. However, it was determined that the eprinomectin clearance from the body may vary depending on the breed in goats. The faecal eprinomectin concentration of Saanen and Alpine goats was 90 and 80 times higher than the plasma eprinomectin concentration, respectively. Although high faecal excretion of eprinomectin confers a high efficacy advantage against parasites in the gastrointestinal tract, it may pose an ecotoxicological risk to manure fauna and aquatic organisms with high susceptibility to this compound.

The efficacy and safety of alphacypermethrin as a pour-on treatment for water buffalo (Bubalus bubalis) infested with Haematopinus tuberculatus (Phthiraptera: Haematopinidae).

The sucking louse Haematopinus tuberculatus (Burmeister 1839) is an ectoparasite of buffaloes, cattle, camels, and American bison. Alphacypermethrin (ACYP) is a pyrethroid insecticide commonly used to control arthropods of veterinary and public health interest. Therapeutics, such as antiparasitic compounds, is often administered to buffaloes based on dosage and intervals recommended for cattle because very few drugs have buffalo-specific label indications. A trial was conducted on 20 louse-infested buffaloes at a farm to assess the efficacy and safety of ACYP pour-on, at the manufacturer's recommended dose for cattle, on buffaloes naturally infested by H. tuberculatus. Ten animals were assigned to ACYP-treated group (ACYP-group) and ten to untreated control group (C-group). On day 0, all ACYP-group buffaloes received alphacypermethrin pour-on. Louse counts were performed on days -1, 7, 14, 21, 28, 35, 42, 49, and 56 at eight predilection sites on the skin of each buffalo. ACYP was completely effective (100%) at day 7, highly effective (99.8%) at day 14, and completely effective (100%) from day 21 until the end of the study (day 56 post-treatment). During the trial, ACYP was well tolerated by all animals as there were no observed clinically adverse reactions. The results of this trial suggest that ACYP is an effective, safe, and user-friendly compound suitable for treatment of buffaloes with natural louse infestations.

Removal of pesticide residues from apple and tomato cuticle.

Pesticide residues are always an unsolved problem in the world despite all kinds of prevention measures. The present research work is based on a scientific hypothesis, i.e., "The removal of average pesticide residue is inversely proportional to the thickness of cuticle." The effects of boron-containing products and plant-based surfactants were tested for the removal of five pesticides (lambda-cyhalothrin, chlorpyrifos, diflubenzuron, metaflumizone, acetamiprid) on tomatoes and apples. Boron-containing products were able to remove the pesticide residues on average between 58.0 and 72.6% in tomatoes and 33.2-58.8% in an apple. While plant-based surfactants removed residues on average between 58.5 and 66.6% in tomatoes and 41.0-53.2% in an apple. The highest removal rate was 72% with etidot at 1%. The solution of 1% C8-C10 provided 66.6% average removal for tomatoes. Less removal was achieved in apples. For an apple, Log Kow and molecular mass (independent variables) were significant with p < 0.01, and the coefficient of determination (R2) was > 0.87. However, the multiple linear regression analysis for ground colemanite was significant with R2 of 0.96. In tomatoes, neither Log Kow nor molecular mass as significant. The correlation was found between the physical and chemical properties of pesticides, but it is estimated that the thickness of the cuticle is effective in removing pesticides.

Efficacy of alphacypermetrin pour-on against natural Werneckiella equi infestation on donkeys (Equus asinus).

The chewing louse Werneckiella equi is an ectoparasite of donkeys and other equids. Alphacypermethrin (ACYP) is a pyrethroid insecticide commonly used for the control of insects of veterinary and public health concerns. A trial was conducted to assess the efficacy of ACYP against W. equi on naturally infested donkeys. Parasitological investigations were performed on 13 animals. On day 0, the donkeys received ACYP pour-on at the manufacturer's recommended dose rate for cattle. Louse counts were performed on days -1, 7, 14, 21, 28, 35, 42, 49, and 56 at seven predilection sites on the skin of each donkey. ACYP was completely effective (100 %) from day 7, until the end of the study. ACYP was well tolerated by all animals as there were no observed clinical adverse reactions. ACYP was highly effective, safe, user-friendly, and considered to be suitable for the treatment of donkeys for W. equi infestation.

Transcutaneous measurement of bilirubin in Turkish newborns: comparison with total serum bilirubin.

Routine use of transcutaneous bilirubin (TcB) measurement in the newborn nursery could reduce costs, readmission rates for hyperbilirubinemia and the need for total serum bilirubin (TSB) measurements. The aim of this study was to examine the correlation between TcB measurement, as performed using BiliCheck, and TSB, measured with high-pressure liquid chromatography (HPLC) and with standard laboratory methods, and to determine the TcB cutoff points with desirable sensitivity and specificity values for various clinically relevant TSB levels by HPLC. Fifty-four infants of > or = 30 weeks of gestational age were enrolled in the study. Near simultaneous blood collection for TSB analysis by three methods--bedside bilirubinometer, diazo method and HPLC--and TcB measurement were performed. There was good correlation between TcB and HPLC-bilirubin (B) (r = 0.85), TSB by bilirubinometer and HPLC-B (r = 0.91) and TSB by diazo method and HPLC-B (r = 0.91). The cut-off limits providing a sensitivity of 100% for TcB measurements were TcB > or = 9 mg/dl for HPLC-B > 17 mg/dl and TcB > or = 8 mg/dl for HPLC-B > 15 mg/dl and HPLC-B > 13 mg/dl. Despite having good correlation with HPLC, BiliCheck showed worse performance than bilirubinometer and diazo method at various clinically relevant cut-off values. Since BiliCheck required relatively lower thresholds with false-positive results for having a sensitivity of 100%, it cannot be recommended as a complete substitute for serum bilirubin measurements.

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.

Contents and sources of DDT impurities in dicofol formulations in Turkey.

BACKGROUND, AIM, AND SCOPE: Dicofol is widely used as a pesticide in agriculture applications. Since dicofol is mainly synthesized from dichlorodiphenyltrichlorethane (DDT), it contains DDT as an impurity. The European Community has forced Prohibition Directive 79/117/EEC to reduce DDT in dicofol formulations. Specifically, DDT content in a dicofol formulation cannot exceed 0.1%. The goal of this project was to determine the DDT content in dicofol formulations used in Turkey. MATERIALS AND METHODS: Samples of all the dicofol formulations in Turkey were collected to quantify DDT and DDT-related compounds. Four replicates were used for each sample. GC/MS/MS was used to analyze p,p' and o,p' isomers of DDT, DDD, and DDE. A HPLC was used to determine p,p'-Cl-DDT concentrations. RESULTS: The total DDT content of the formulated dicofol was found between 0.3% and 14.3%. The concentration of p,p'-DDE ranged from 167 to 1,042 mg kg(-1) in dicofol samples. p,p'-DDT concentrations were found to be 32 to 183 mg kg(-1). The o,p'-DDT level ranged from 2 to 34 mg kg(-1) in the dicofol formulations analyzed. DISCUSSION: It was estimated that 617.8 kg of DDT was released from dicofol. The main impurity was identified as p,p-Cl-DDT. Based on these results, dicofol serves as a continuing source of DDT contamination. CONCLUSIONS: All DDT concentrations in dicofol samples analyzed were higher than the permitted 0.1% level of Prohibition Directive 79/117/EEC. The reduction of dicofol is critical since it serves as a continual source of DDT contamination. RECOMMENDATIONS AND PERSPECTIVES: DDT has been found in soil, water, and air samples. Dicofol has been identified as a contributor to continued DDT contamination in soil and water. More studies are needed to ascertain the source of DDT in the air.

Anthelmintic drugs used in equine species.

Internal parasites of horses comprise an intractable problem conferring disease, production and performance losses. Parasitism can rarely be controlled in grazing horses by management alone and anthelmintic drugs have formed the basis of therapy and prophylaxis for the last sixty years. The pharmacology of the anthelmintic drugs available dictate their spectrum of activity and degree of efficacy, their optimal routes of administration and characteristics which prevent some routes of administration, their safety tolerance and potential toxicities and as a consequence of their persistence in the body at effective concentrations their use in epidemiological control programmes. Their use has also resulted in the selection of parasites with genetically controlled characteristics which reduce their susceptibility to treatment, characteristics which are often common to whole chemical classes of anthelmintics. Pharmacological properties also confer compatibility in terms of safety and persistence with other anthelmintic drugs and thus the potential of combinations to treat parasites from different phylogenetic groups such as nematodes, cestodes and trematodes and also the potential by agency of their different molecular mechanisms of action to delay the selection of resistant genes. The major groups of anthelmintics now available, the benzimidazoles (BZD), macrocyclic lactones (MLs) and tetrahydropyrimidines are all highly effective against their targeted parasites (primarily nematodes for BZD's and ML's and cestodes for tetrahydropyrimidines) easily administered orally to horses and are well tolerated with wide margins of safety. Nevertheless, some parasitic stages are inherently less susceptible such as hypobiotic stages of the small strongyles (cyathostomins) and for some such as the adult stages of cyathostomins resistance has developed. Furthermore, for some less common parasites such as the liver fluke unlicensed drugs such as the salicylanilide, closantel have been used. A deep understanding of the pharmacology of anthelmintic drugs is essential to their optimal use in equine species.

The effect of diet type on the plasma disposition of triclabendazole in goats.

The effect of two different diet types (concentrate feed+hay and grazing) on the pharmacokinetic profiles of triclabendazole following oral administration in goats was investigated. A total of 12 goats were randomly allocated into two groups which were either indoor and fed concentrate + hay ration (housed group) or were grazing on pasture (grazing group). Triclabendazole was administered orally to animals in two groups at 10 mg/kg bodyweight. Blood samples were collected from 1 h to 192 h post-treatment and analyzed by high performance liquid chromatography (HPLC). Feeding with different diets significantly effected the plasma disposition of triclabendazole sulphoxide. Maximum plasma concentration (C(max): 13.22+/-2.81 microg/ml), time to reach maximum plasma concentration (t(max): 18.4+/-2.19 h), area under the curve (AUC: 613+/-137 microg h/ml), half-life (t(1/2): 24.77+/-1.94 h) and mean resident time (MRT: 40.22+/-4.36 h) of triclabendazole sulphoxide in housed group were significantly different from those of grazing group (C(max): 10.17+/-1.51 microg/ml, t(max): 14.0+/-2.19 h, AUC: 406+/-98 microg h/ml), t(1/2): 16.16+/-1.17 h and MRT: 34.48+/-4.40 h). It is concluded that anthelmintically more active sulphoxide metabolite has higher plasma concentration when triclabendazole is administered to goats fed with concentrate feed + hay compared to grazing goats.

Comparative plasma dispositions of ivermectin and doramectin following subcutaneous and oral administration in dogs.

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.

Plasma disposition and faecal excretion of oxfendazole, fenbendazole and albendazole following oral administration to donkeys.

Fenbendazole (FBZ), oxfendazole (fenbendazole sulphoxide, FBZSO), and albendazole (ABZ) were administered orally to donkeys at 10mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment. The plasma and faecal samples were analysed by high performance liquid chromatography (HPLC). The parent molecule and its sulphoxide and sulphone (FBZSO(2)) metabolites did not reach detectable concentrations in any plasma samples following FBZ administration. ABZ was also not detected in any plasma samples, but its sulphoxide and sulphone metabolites were detected, demonstrating that ABZ was completely metabolised by first-pass mechanisms in donkeys. Maximum plasma concentrations (C(max)) of FBZSO (0.49microg/mL) and FBZSO(2) (0.60microg/mL) were detected at (t(max)) 5.67 and 8.00h, respectively, following administration of FBZSO. The area under the curve (AUC) of the sulphone metabolite (10.33microg h/mL) was significantly higher than that of the parent drug FBZSO (5.17microg h/mL). C(max) of albendazole sulphoxide (ABZSO) (0.08g/mL) and albendazole sulphone (ABZSO(2)) (0.04microg/mL) were obtained at 5.71 and 8.00h, respectively, following ABZ administration. The AUC of the sulphoxide metabolite (0.84microg h/mL) of ABZ was significantly higher than that of the sulphone metabolite (0.50microg h/mL). The highest dry-faecal concentrations of parent molecules were detected at 32, 34 and 30h for FBZSO, FBZ and ABZ, respectively. The sulphide metabolite was significantly higher than the parent molecule after FBZSO administration. The parent molecule was predominant in the faecal samples following FBZ administration. After ABZ administration, the parent molecule was significantly metabolised, probably by gastrointestinal microflora, to its sulphoxide metabolite (ABZSO) that showed a similar excretion profile to the parent molecule in the faecal samples. The AUC of the parent FBZ was significantly higher than that of FBZSO and ABZ in faeces. It is concluded that the plasma concentration of FBZSO was significantly higher than that of FBZ and ABZ. Although ABZ is not licensed for use in Equidae, its metabolites presented a greater plasma kinetic profile than FBZ which is licensed for use in horses. A higher metabolic capacity, first-pass effects and lower absorption of benzimidazoles in donkeys decrease bioavailability and efficacy compared to ruminants.

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.

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).