Plasma dispositions and concentrations of ivermectin in eggs following treatment of laying hens.

AIMS: To determine the plasma disposition and concentrations of ivermectin (IVM) in eggs produced by laying hens following S/C, oral and I/V administration. METHODS: Twenty-four laying hens, aged 37 weeks and weighing 1.73 (SD 0.12) kg were allocated to three groups of eight birds. The injectable formulation of IVM was administered either orally, S/C, or I/V, at a dose of 0.2 mg/kg liveweight, following dilution (1:5, v/v) with propylene glycol. Heparinised blood samples were collected at various times between 0.25 hours and 20 days after drug administration. Eggs produced by hens were also collected daily throughout the study period. Samples of plasma and homogenised egg were analysed using HPLC. RESULTS: Maximum concentrations of IVM in plasma and mean residence time of IVM were lower after oral (10.2 (SD 7.2) ng/mL and 0.38 (SD 0.14) days, respectively) than after S/C (82.9 (SD 12.4) ng/mL and 1.05 (SD 0.24) days, respectively) administration (p<0.01). The time to maximum concentration and elimination half-life were shorter following oral (0.14 (SD 0.04) and 0.23 (SD 0.11) days, respectively) than S/C (0.25 (SD 0.00) and 1.45 (SD 0.45) days, respectively) administration (p<0.01). IVM was first detected in eggs 2 days after treatment in all groups and was detected until 8 days after oral and I/V administration, and until 15 days after S/C administration. Peak concentrations of IVM were 15.7, 23.3 and 1.9 µg/kg, observed 2, 5 and 4 days after I/V, S/C and oral administration, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The low plasma bioavailability of IVM observed after oral administration in laying hens could result in lower efficacy or subtherapeutic plasma concentrations, which may promote the development of parasitic drug resistance. Due to high IVM residues in eggs compared to the maximum residue limits for other food-producing animal species, a withdrawal period should be necessary for eggs after IVM treatment in laying hens.

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

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

Plasma disposition and faecal excretion of eprinomectin following topical and subcutaneous administration in non-lactating dairy cattle.

AIMS: To investigate the plasma disposition and faecal excretion of eprinomectin (EPM) in non-lactating dairy cattle following topical and S/C administration. METHODS: Holstein dairy cows, 3.5-5 years-old, were selected 20-25 days after being dried off and were randomly allocated to receive EPM either topically (n=5) or S/C (n=5) at dose rates of 0.5 and 0.2 mg/kg bodyweight, respectively. Heparinised blood and faecal samples were collected at various times between 1 hour and 30 days after treatment, and were analysed for concentrations of EPM using high performance liquid chromatography with a fluorescence detector. RESULTS: The maximum concentration of EPM in plasma (Cmax) and the time to reach Cmax were both greater after S/C administration (59.70 (SD 12.90) ng/mL and 1.30 (SD 0.27) days, respectively) than after topical administration (20.73 (SD 4.04) ng/mL and 4.40 (SD 0.89) days, respectively) (p<0.001). In addition, S/C administration resulted in greater plasma availability (area under the curve; AUC), and a shorter terminal half-life and mean residence time (295.9 (SD 61.47) ng.day/mL; 2.95 (SD 0.74) days and 4.69 (SD 1.01) days, respectively) compared with topical administration (168.2 (SD15.67) ng.day/mL; 4.63 (SD 0.32) days, and 8.23 (SD 0.57) days, respectively) (p<0.01). EPM was detected in faeces between 0.80 (SD 0.45) and 13.6 (SD 4.16) days following S/C administration, and between 1 (SD 0.5) and 20.0 (SD 3.54) days following topical administration. Subcutaneous administration resulted in greater faecal excretion than topical administration, expressed as AUC adjusted for dose (1188.9 (SD 491.64) vs. 311.5 (SD 46.90) ng.day/g; p<0.05). Maximum concentration in faeces was also higher following S/C than topical administration (223.0 (SD 63.96) vs. 99.47 (SD 43.24) ng/g; p<0.01). CONCLUSIONS: Subcutaneous administration of EPM generated higher plasma concentrations and greater plasma availability compared with topical administration in non-lactating cattle. Although the S/C route provides higher faecal concentrations, the longer faecal persistence of EPM following topical administration may result in more persistent efficacy preventing establishment of incoming nematode larvae in cattle.

Plasma disposition of enrofloxacin following intravenous and intramuscular administration in donkeys.

This study was designed to investigate the plasma disposition and systemic availability of enrofloxacin (ENR) following intramuscular and intravenous administrations. Six donkeys (Equus asinus) were used in this study. The animals were allocated into two groups (intramuscular and intravenous groups). After a 2-week washout period, the experiment was repeated with the groups reversed according to a two-phase crossover design. In phase I, group I received intravenously the commercially available injectable solution of ENR at the dose of 5 mg/kg and group II received intramuscularly the same ENR formulation at the same dose rate. Blood samples were collected 1 hour prior to drug administration and various times between 5 minutes and 48 hours post-treatments. The samples were analysed by high performance liquid chromatography with fluorescence detector. The half-life and mean residence time of ENR (12.08 hours and 17.85 hours) after intramuscular route were significantly longer compared with intravenous administration (9.54 hours and 7.46 hours, respectively) and these were associated with a flip-flop phenomenon. A marked proportion of ENR (20-21 per cent) was metabolised to ciprofloxacin (CPR) following both administration routes and the half-life of CPR paralleled that of the parent drug after intramuscular administration. Mean absorption time was relatively long (10.39 hours), and the bioavailability of ENR was 76.56 per cent after intramuscular route in the donkeys. The plasma concentration is lower after intramuscular administration at a dose rate of 5 mg/kg, and may need a higher dose to provide sufficient plasma concentration in donkeys compared with horses.

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

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

Plasma dispositions of ivermectin, doramectin and moxidectin following subcutaneous administration in rabbits.

This study evaluated the comparative plasma dispositions of ivermectin (IVM), doramectin (DRM) and moxidectin (MXD) following subcutaneous administration in rabbits. Fifteen New Zealand white rabbits were allocated into three groups of five animals each. The animals in each group received IVM, DRM or MXD by subcutaneous injection at a single dose of 0.3 mg/kg. Blood samples were collected at various times between 1 h and 40 days after treatment and the plasma samples were analysed by high-performance liquid chromatography using fluorescence detection. Moxidectin was absorbed faster from the injection site and reached the peak plasma concentration (C(max)) significantly earlier than IVM and DRM. There was no significant difference in C(max) values among the three molecules, whereas the area under the concentration-time curves of DRM (258.40 ng.d/mL) and IVM (191.62 ng.d/mL) was significantly higher than that of MXD (83.17 ng.d/mL). The mean plasma residence time and terminal half-life (t(1/2lambdaz)) were longer for DRM (7.52 and 4.48 days, respectively) and MXD (8.97 and 8.16 days, respectively) compared with IVM (4.73 and 2.75 days, respectively). Considering the pharmacokinetic parameters for the parent molecules, the persistence of DRM and MXD are significantly longer than IVM and this may have a positive effect on their efficacy in rabbits following subcutaneous administration or utility relating to interdosing interval.

Persistence and behavior of pesticides in cotton production in Turkish soils.

Turkey is the sixth largest producer of cotton in the world. Two of the most commonly applied pesticides used in cotton production are trifluralin and endosulfan. Although both are very effective at controlling pests, their persistence in the environment poses risks to human health and the environment. Four loam soils and one silty-loam soil were studied to evaluate the persistence of trifluralin and endosulfan in relation to soil characteristics. Degradation with trifluralin reached as high as 70% of the applied doses. Soils with the highest organic matter content had the lowest degradation rate, indicating a tighter sorption of trifluralin. Endosulfan degradation was a function of soil type and the specific isomer, with beta-endosulfan depicting the highest degradation.

Effect of pharynx epithelial cells surface desialylation on receptor-mediated adherence of Staphylococcus aureus.

AIMS: To characterize the interaction between cell surface carbohydrates and Staphylococcus aureus. METHODS AND RESULTS: In the present study, in vitro adherence of S. aureus to Detroit 562 cells, amount of cell surface desialylation and effect of subterminal monosaccharides on desialylated glycoproteins on adherence was studied with colony counting, HPLC, fluorescence microscopy and fluorometric techniques. According to our findings, S. aureus adherence to pharynx cells was enhanced (40%) after neuraminidase treatment, and neuraminidase also cleave great amount of Detroit 562 cells surface sialic acid (39-60%). Adherence assay with various monosaccharides-pretreated bacteria, and lectin competitive inhibition, showed that the residual subterminal galactose, fucose and N-acetyl-D-glucosamine remaining on desialylated Detroit 562 cell surface glycoproteins responsible for this binding. CONCLUSION: The results are the first to show that galactose, fucose and N-acetyl-D-glucosamine remaining on desialylated pharynx cell surface glycoproteins serve as the adhesine receptors for S. aureus. SIGNIFICANCE AND IMPACT OF THE STUDY: This study may explain the predisposition of severe S. aureus pneumonia complication in respiratory viral infections.

Pharmacological assessment of netobimin as a potential anthelmintic for use in horses: plasma disposition, faecal excretion and efficacy.

This study aimed to determine the plasma disposition and faecal excretion of netobimin (NTB) and its respective metabolites as well as the efficacy against strongyles in horses following oral administration. Netobimin (10mg/kg) was administered orally to 8 horses. Blood and faecal samples were collected from 1 to 120h post-treatment and analysed by high performance liquid chromatography (HPLC). Using a chiral phase-based HPLC, plasma disposition of ABZSO enantiomers produced was also determined. Faecal strongyle egg counts (EPG) were performed by a modified McMaster's technique before and after the treatment. Neither NTB nor ABZ were present and only albendazole sulphoxide (ABZSO) and sulphone metabolites (ABZSO(2)) were detected in the plasma samples. Maximum plasma concentration of ABZSO (0.53+/-0.14microg/ml) and ABZSO(2) (0.36+/-0.09microg/ml) were observed at (t(max)) 10.50 and 19.50h, respectively following administration of NTB. The area under the curve (AUC) of the two metabolites was similar to each other. Netobimin was not detected, and ABZ was predominant in faecal samples. The maximum plasma concentration (C(max)) of (-)ABZSO was significantly higher than (+)ABZSO, but the area under the curves (AUCs) of the enantiomer were not significantly different each other in plasma samples. The enantiomers of ABZSO were close to racemate in the faecal samples analyzed. Netobimin reduced the EPG by 100%, 100%, 77%, 80% and 75% 2, 4, 6, 8 and 10 weeks post-treatment, respectively. The specific behaviour of the two enantiomers probably reflects different enantioselectivity of the enzymatic systems of the liver which are responsible for sulphoxidation and sulphonation of ABZ. Considering the pharmacokinetic and efficacy parameters NTB could be used as an anthelmintic in horses.

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.

Comparative plasma disposition of fenbendazole, oxfendazole and albendazole in dogs.

The plasma disposition of fenbendazole (FBZ), oxfendazole (OFZ) and albendazole (ABZ); and the enantiospecific disposition of OFZ, and ABZSO produced were investigated following an oral administration (50 mg/kg) in dogs. Blood samples were collected from 1 to 120 h post-administration. The plasma samples were analysed by high performance liquid chromatography (HPLC). The plasma concentration of FBZ, OFZ, ABZ and their metabolites were significantly different from each other and depended on the drug administered. The sulphone metabolite (FBZSO2) of FBZ was not detected in any plasma samples and the parent molecule ABZ did not reach quantifiable concentrations following FBZ and ABZ administration, respectively. OFZ and its sulphone metabolite attained a significantly higher plasma concentration and remained much longer in plasma compared with FBZ and ABZ and their respective metabolites. The maximum plasma concentrations (Cmax), area under the concentration time curve (AUC) and mean residence time (MRT) of parent OFZ were more than 30, 68 and 2 times those of FBZ, respectively. The same parameters for ABZSO were also significantly greater than those of FBZSO. The ratio for total AUCs of both the parent drug and the metabolites were 1:42:7 for following FBZ, OFZ and ABZ administration, respectively. The enantiomers were never in racemic proportions and (+) enantiomers of both OFZ and ABZSO were predominant in plasma. The AUC of (+) enantiomers of OFZ and ABZSO was, respectively more than three and seven times larger than that of (-) enantiomers of both molecules. It is concluded that the plasma concentration of OFZ was substantially greater compared with FBZ and ABZ. The data on the pharmacokinetic profile of OFZ presented here may contribute to evaluate its potential as an anthelmintic drug for parasite control in dogs.

Plasma disposition and faecal excretion of netobimin metabolites and enantiospecific disposition of albendazole sulphoxide produced in ewes.

Netobimin (NTB) was administered orally to ewes at 20 mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment and analysed by high-performance liquid chromatography (HPLC). Using a chiral phase-based HPLC, plasma disposition of albendazole sulphoxide (ABZSO) enantiomers produced was also determined. Neither NTB nor albendazole (ABZ) was present and only ABZSO and albendazole sulphone (ABZSO(2)) metabolites were detected in the plasma samples. Maximum plasma concentrations (C(max)) of ABZSO (4.1 +/- 0.7 microg/ml) and ABZSO(2) (1.1 +/- 0.4 microg/ml) were detected at (t(max)) 14.7 and 23.8 h, respectively following oral administration of netobimin. The area under the curve (AUC) of ABZSO (103.8 +/- 22.8 (microg h)/ml) was significantly higher than that ABZSO(2)(26.3 +/- 10.1 (microg h)/ml) (p < 0.01). (-)-ABZSO and (+)-ABZSO enantiomers were never in racemate proportions in plasma. The AUC of (+)-ABZSO (87.8 +/- 20.3 (microg h)/ml) was almost 6 times larger than that of (-)-ABZSO (15.5 +/- 5.1 (microg h)/ml) (p < 0.001). Netobimin was not detected, and ABZ was predominant and its AUC was significantly higher than that of ABZSO and ABZSO(2), following NTB administration in faecal samples (p > 0.01). Unlike in the plasma samples, the proportions of the enantiomers of ABZSO were close to racemic and the ratio of the faecal AUC of (-)-ABZSO (172.22 +/- 57.6 (microg h)/g) and (+)-ABZSO (187.19 +/- 63.4 (microg h)/g) was 0.92. It is concluded that NTB is completely converted to ABZ by the gastrointestinal flora and absorbed ABZ is completely metabolized to its sulphoxide and sulphone metabolites by first-pass effects. The specific behaviour of the two enantiomers probably reflects different enantioselectivity of the enzymatic systems of the liver that are responsible for sulphoxidation and sulphonation of ABZ.

Plasma pharmacokinetics and faecal excretion of ivermectin (Eqvalan paste) and doramectin (Dectomax, 1%) following oral administration in donkeys.

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

Fenbendazole pharmacokinetics, metabolism, and potentiation in horses.

The present study was designed to describe the pharmacokinetics and fecal excretion of fenbendazole (FBZ) and fenbendazole sulphoxide (FBZSO) and their metabolites in horses, to investigate the effects which concurrent feeding has on the absorption and pharmacokinetics of FBZ, and to determine the effect of coadministration of the metabolic inhibitor piperonyl-butoxide on the in vivo pharmacokinetics and in vitro liver microsomal metabolism of sulfide and sulfoxide benzimidazoles. The effect of piperonyl-butoxide on the enantiomeric genesis of the sulfoxide moiety was also investigated. Following administration of FBZSO and FBZ, the fenbendazole sulphone metabolite predominated in plasma, and the C(max) and area under the plasma curve (AUC) values for each moiety were larger (P < 0.001) following FBZSO than FBZ. In feces the administered parent molecule predominated. The combined AUC for active benzimidazole moieties following oral administration of FBZ (10 mg/kg) in horses was almost 4 times as high in unfed horses (2.19 microg x h/ml) than in fed horses (0.59 microg x h/ml), and coadministration of piperonyl-butoxide significantly increased the AUC and C(max) of active moieties following intravenous administration of FBZSO and oral administration of FBZ. When FBZSO was administered i.v. as a racemate, the first enantiomer of oxfendazole (FBZSO-1) predominated in plasma, however, following coadministration with piperonyl-butoxide, the second enantiomer of oxfendazole (FBZSO-2) predominated for 10 h. Piperonyl-butoxide significantly reduced the oxidative metabolism of FBZSO and FBZ in equine liver microsomes and altered the ratio of enantiomers FBZSO-1/FBZSO-2 from >4:1 to 1:1. It is concluded that in horses efficacy of FBZSO and FBZ could be improved by administration to unfed animals and coadministration with piperonyl-butoxide.

Plasma disposition, faecal excretion and in vitro metabolism of oxibendazole following oral administration in horses.

Oxibendazole (OBZ) was administered to eight horses at an oral dose of 10 mg kg(-1) bodyweight each. Parent OBZ could only be detected in plasma at the 0.5 and 1.0 hours post administration sampling times and the mean maximum plasma concentration was 0.008 microg ml(-1). Parent OBZ was detected in faeces between 12 and 72 hours after administration and the highest dry faecal concentration was detected at 24 hours. An unidentified metabolite was detected in plasma between 0.5 and 72 hours. The unidentified metabolite in the plasma of treated horses corresponded to the second eluted metabolite in the in vitro study. Metabolism of OBZ to its metabolite in vitro was significantly inhibited by co-incubation with the cytochrome P450 inhibitor piperonyl butoxide. These results indicated that first-pass metabolism decreases OBZ bioavailability in horses. The in vitro metabolism of OBZ was significantly inhibited by piperonyl butoxide and this could be utilised to extend the exposure of nematodes to the parent molecule.

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

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