Formulation Of Ivermectin Research Articles

A comparison of the efficacy of two ivermectin formulations against larval and adult Ascaris suum and Oesophagostomum dentatum in experimentally infected pigs

A study was conducted to evaluate and compare the efficacy of two injectable formulations of ivermectin (IVM-1 and IVM-2) at a dose rate of 0.3 mg/kg bodyweight versus placebo in the treatment and control of larval and adult stages of Ascaris suum and Oesophagostomum spp. in experimentally infected pigs. Seventy helminth free pigs were allocated on a liveweight basis to 7 groups each comprising 10 pigs (A–G). Group A served as an untreated control group. Groups B and C were used to investigate the efficacy of both formulations against adult stages of A. suum and Oesophagostomum spp., Groups D and E for efficacy against larval stages of A. suum and Groups F and G for efficacy against larval stages of Oesophagostomum spp. Pigs of groups A, B, C, D and E were infected on Day-0 with 1000 infective A. suum eggs each. Infective larvae of Oesophagostomum spp. (10,000/pig) were given on Day-0 to pigs of Groups F and G and on Day-21 to pigs of Groups A, B and C. Treatment was given to pigs of Group A (saline as placebo) on Day-7 and -28, IVM-1 to pigs of Group F on Day-7, pigs of Group D on Day-14 and pigs of Group B on Day-49. IVM-2 was given to pigs of Group G on Day-7, Group E on Day-28 and Group C on Day-49. Pigs of Groups F and G were sacrificed on Day-28, pigs of Groups A, D and E on Day-49 and pigs of Groups B and C on Day-56. Post mortem worm counts showed the following efficacies: (IVM-1) against larval A. suum 100%, against adult A. suum 94.4%, against larval Oesophagostomum spp. 52.0% and against adult Oesophagostomum spp. 83.0%. (IVM-2) against larval A. suum 100%, against adult A. suum 90.3%, against larval Oesophagostomum spp. 94.0% and against adult Oesophagostomum spp. 94.7%.

Bioavailability of a commercial formulation of ivermectin after subcutaneous administration to sheep

Bioavailability of a commercial formulation of ivermectin after subcutaneous administration to sheep

Bioavailability of a commercial formulation of ivermectin after subcutaneous administration to sheep

To evaluate bioavailability and other pharmacokinetic variables of a commercial formulation of ivermectin after IV administration to sheep. 6 healthy adult sheep. A single dose of a commercial formulation of ivermectin (200 microg/kg) was administered IV to each sheep. After a washout period of 3 weeks, each sheep was administered ivermectin by SC injection. Plasma samples were obtained for up to 36 and up to 42 days after IV and SC administration, respectively. Ivermectin concentrations were quantified by use of high-performance liquid chromatography with fluorescence detection. Results obtained indicated that after IV administration, ivermectin is cleared slowly from plasma, tends to distribute and accumulate in the peripheral compartment, and is slowly eliminated from the body. After SC administration, noncompartmental analysis revealed that bioavailability of ivermectin is nearly complete (98.20%), has a slow mean absorption time of 0.96 days, and reaches a maximum plasma concentration of 19.55 ng/mL at 3.13 days. The commercial formulation of ivermectin used in this study can be administered SC to sheep on the basis of a nearly complete bioavailability. In addition, the maximum plasma concentration and interval from SC injection until maximum plasma concentration is obtained are higher than those reported by other authors who used other routes of administration.

Larval immersion tests with ivermectin in populations of the cattle tick Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) from State of Sao Paulo, Brazil

Larval immersion tests (LIT) with commercial formulation of ivermectin were carried out with larvae of two field populations of Rhipicephalus (Boophilus) microplus from commercial dairy farms of the State of Sao Paulo, Brazil and a susceptible strain (Porto Alegre) to differentiate resistant-suspected and susceptible strains. One of the populations tested (Barra Alegre) showed a LC 50 value significantly higher than the susceptible strain and a resistance ratio (CI95%) of 3.78 (3.47–4.12), leading to suspect that this population shows traces of resistance to ivermectin. Population Sao Francisco, with no records of ivermectin injections on cattle, showed no difference on the ivermectin response in relation to Porto Alegre strain characterizing it as susceptible. Although LIT is not yet recommended by FAO to diagnose resistance to acaricides, this technique was successful on the differentiation of resistance-suspected population and a susceptible strain and can be used to detect populations of R. (B.) microplus resistant to ivermectin. This is the first report of R. (B.) microplus resistant to ivermectin detected by an in vitro bioassay.

Pharmacokinetics of a novel formulation of ivermectin after administration to goats

To evaluate the pharmacokinetics of a novel commercial formulation of ivermectin after administration to goats. 6 healthy adult goats. Ivermectin (200 microg/kg) was initially administered IV to each goat, and plasma samples were obtained for 36 days. After a washout period of 3 weeks, each goat received a novel commercial formulation of ivermectin (200 microg/kg) by SC injection. Plasma samples were then obtained for 42 days. Drug concentrations were quantified by use of high-performance liquid chromatography with fluorescence detection. Pharmacokinetics of ivermectin after IV administration were best described by a 2-compartment open model; values for main compartmental variables included volume of distribution at a steady state (9.94 L/kg), clearance (1.54 L/kg/d), and area under the plasma concentration-time curve (AUC; 143 [ng x d]/mL). Values for the noncompartmental variables included mean residence time (7.37 days), AUC (153 [ng x d]/mL), and clearance (1.43 L/kg/d). After SC administration, noncompartmental pharmacokinetic analysis was conducted. Values of the variables calculated by use of this method included maximum plasma concentration (Cmax; 21.8 ng/mL), time to reach Cmax (3 days), and bioavailability (F; 91.8%). The commercial formulation used in this study is a good option to consider when administering ivermectin to goats because of the high absorption, which is characterized by high values of F. In addition, the values of Cmax and time to reach Cmax are higher than those reported by other investigators who used other routes of administration.

Assessment of a liposomal formulation of ivermectin in rabbit after a single subcutaneous administration

Ivermectin is a member of the macrocyclic lactone family widely used in livestock, pets, and humans as a potent parasiticide. Slight differences in formulation may change the plasma kinetics and efficacy of these compounds. The aim of the study is to evaluate the ability of a liposomal formulation of ivermectin to generate an efficient exposure of the animal to the drug. Ten rabbits were subcutaneously administered with 0.3 mg kg(-1) of ivermectin using Ivomec (n=5) or a liposomal formulation (n=5). The areas under serum concentration-time curve were similar after both treatments, indicating the same bioavailability for the two formulations. However, the liposomal formulation gave a higher C(max) value (33.33 ng ml(-1)) compared with Ivomec (20.82 ng ml(-1)) and a significantly faster absorption as indicated by the T(max) of 0.23 days compared with 1.13 days for the Ivomec formulation. The use of liposomal formulation shows promise as this system improves the efficacy of ivermectin and related drugs.

Fatal Outcome of a Hyperinfection Syndrome despite Successful Eradication of Strongyloides with Subcutaneous Ivermectin

We report the case of a 77–year–old man who developed a Strongyloides hyperinfection syndrome following immunosuppressive therapy more than 60 years after he moved away from an area endemic for Strongyloides stercoralis. Successful eradication of the nematode was achieved with an off label subcutaneous formulation of ivermectin. However, the patient subsequently died from acute respiratory distress syndrome (ARDS). Despite a high wormload in the stool and sputum of the patient and delayed infection control measures in the hospital, testing of the medical staff revealed a very low risk of Strongyloides transmission among healthcare workers.

Doramectin concentration profiles in the gastrointestinal tract of topically-treated calves: Influence of animal licking restriction

Endectocide compounds are extensively used for broad-spectrum parasite control and their topical administration to cattle is widespread in clinical practice. Pour-on formulations of moxidectin, ivermectin, eprinomectin and doramectin (DRM) are marketed internationally for use in cattle. However, variability in antiparasitic efficacy and pharmacokinetic profiles has been observed. Although the tissue distribution pattern for different endectocide molecules given subcutaneously to cattle has been described, only limited information on drug concentration profiles in tissues of parasite location after topical treatment is available. Understanding the plasma and target tissue kinetics for topically-administered endectocide compounds is relevant to optimise their therapeutic potential. The current work was designed to measure the plasma and gastrointestinal (GI) concentration profiles of DRM following its pour-on administration to calves. The influence of natural licking behaviour of cattle on DRM concentration in mucosal tissue and luminal content of different GI sections was evaluated. The trial was conducted in two experimental phases. In Phase I, the DRM plasma kinetics was comparatively characterised in free-licking and in 2-day licking-restricted (non-licking) calves. The pattern of distribution of topical DRM to mucosal and luminal contents from abomasum, duodenum, ileum, caecum and spiral colon was assessed in free-licking and non-licking calves restricted over 10 days post-administration (Phase II). The prevention of licking caused marked changes on the plasma and GI kinetics of DRM administered pour-on. In 2-day licking restricted calves, DRM systemic availability was significantly lower (29%) than in free licking animals during the first 9 days post-treatment. Following a 10-day long licking restriction period, DRM concentrations profiles in both mucosal tissue and luminal contents of the GI tract were markedly higher in animals allowed to lick freely. This enhancement in drug concentrations in free-licking compared to non-licking calves, was particularly pronounced in the abomasal (38-fold higher) and duodenal (six-fold higher) luminal content. As shown earlier for ivermectin, licking behaviour may facilitate the oral ingestion of topically-administered DRM in cattle. This would be consistent with the marked lower drug concentration profiles measured in the bloodstream and GI tract of the animals prevented from licking. The work reported here provides relevant information on the pattern of DRM distribution to the GI tract after pour-on treatment, and contributes to understand the variability observed in the antiparasitic persistence of topically-administered endectocides in cattle. The implications of natural licking in topical treatments are required to be seriously assessed to achieve optimal parasite control and to design parasitological and pharmacological studies within the drug approval process.

Treatment of Human Disseminated Strongyloidiasis with a Parenteral Veterinary Formulation of Ivermectin

There are no parenteral antihelminthic drugs licensed for use in humans. We report the successful treatment of disseminated strongyloidiasis with a parenteral veterinary formulation of ivermectin in a patient presenting with severe malabsorption and paralytic ileus. To our knowledge, ivermectin levels are reported for the first time in this situation.

Comparative study of the efficacy of eprinomectin versus ivermectin, and field efficacy of eprinomectin only, for the treatment of chorioptic mange in alpacas

The efficacy of eprinomectin versus ivermectin (Study 1: a single-centre, randomised, treatment-controlled, blinded field trial), and the field efficacy of eprinomectin (Study 2: a single-centre, open, un-controlled field trial) for the treatment of chorioptic infestation in naturally infested alpacas were assessed in two studies. Thirty alpacas, all positive for Chorioptes sp. mite, were randomly allocated to two treatment groups in Study 1. Group A received a single topical administration of a 0.5% formulation of eprinomectin at the dose rate of 500 μg/kg. Group B received three subcutaneous administrations at 14 days interval of a 1% formulation of ivermectin at the dose rate of 400 μg/kg. Response to treatment was assessed by periodic mite count, and skin lesions scored. In Study 2, one group of 19 alpacas received four administrations at weekly interval of topical eprinomectin at the dose rate of 500 μg/kg, and response to treatment was monitored by mite counts. No localised or systemic side effects were observed in either trial. There was a statistically significant decrease in mite counts on day 7 ( P < 0.001) within treatment Groups A and B of Study 1, but mite counts increased again on day 14 and remained high for the duration of the trial in both treatment groups. On day 14 of Study 2, there was a statistically significant reduction in mite counts ( P < 0.008) and the mite counts remained very low throughout the remainder of the study. The eprinomectin protocol employed in Study 2, consisting of four weekly topical administrations at the dose rate of 500 μg/kg of body weight, proved highly effective at reducing the Chorioptes mite burden in alpacas.

Evaluation of the Efficacy of Oral Paste Formulations of Ivermectin against Gastrointestinal Parasites in Horses

The anthelmintic efficacy of oral paste formulations of ivermectin against gastrointestinal parasites in horses was evaluated, using fifteen active racehorses in which nematodes had been detected in their gastrointestinal tracts by fecal examination. A single dose of ivermectin was given orally to twelve horses of the treatment groups at a dosage rate of 200 μg/kg in order to obtain and identify gastrointestinal parasites in their feces for 3 days after treatment. Small strongyles, strongyles, and Parascaris equorum were found passed in feces up to post-treatment day (PTD) 2, but they were no longer observed on PTD 3. Horse bot fly Gasterophilus spp. larvae were found on PTD 2 and 3. The percentages of small strongyles found on PTD 1 were 75-100% (88% on average), and the rest were found (12% on average) on PTD 2. The nematodes were 16 species from 7 genera, of which 11 species were identified as small strongyles. In the fecal examination conducted on PTD 14, all horses of the treatment groups showed negative for nematode eggs. No abnormalities were observed in general clinical signs of the treated horses for 14 days after treatment. Three non-treated horses of the control groups still showed positive for nematode eggs on PTD 14. These results confirm that when ivermectin was given orally to horses at a dosage rate of 200 μg/kg, small strongyles, strongyles, and P. equorum, were excreted in feces up to PTD 2, and Gasterophilus spp. larvae on and after PTD 2, demonstrating the potent anthelmintic efficacy of ivermectin against these parasites.

Pharmacokinetics of ivermectin in zebu Gobra ( Bos indicus)

Plasma disposition kinetics of ivermectin was evaluated in a West African cattle breed. Five clinically healthy zebu Gobra cattle ( Bos indicus) weighing 220–270 kg were treated (0.2 mg kg −1) with a commercially available ivermectin formulation for cattle. Blood samples were collected by jugular puncture at different times between 0.5 h and 40 days post-treatment. After plasma extraction and derivatization, samples were analysed by HPLC with fluorescence detection. Ivermectin was detected in plasma between 30 min and 20 days post-treatment. The observed peak plasma concentration ( C max) was 46.3 ± 13.8 ng ml −1 and the time to reach C max ( t max) was 0.9 ± 0.2 day. The values for the absorption half-life ( t 1/2ab) and the elimination half-life ( t 1/2el) were 0.3 ± 0.2 and 2.8 ± 0.7 days, respectively. The calculated area under the concentration–time curve (AUC) was 185.2 ± 12.1 ng day ml −1 and the mean residence time (MRT) was 4.2 ± 1.3 days. The availability of ivermectin is low in zebu Gobra in comparison to other breeds cattle but equivalent to that reported in the yak and is likely to be due to physiological characteristics of this breed.

Ivermectin treatment against gastrointestinal nematodes in New World camelids in Belgium

Gastrointestinal parasites are a major clinical and economical threat to New World camelids (NWC) throughout the world. Since there are no anthelmintics approved for use in NWC, there is only limited information about the efficacy and safety of these products. In this study, the reduction of the faecal egg output following treatment with an injectable formulation of ivermectin in NWC was evaluated. Therefore, a group of 10 llamas and a group of eight alpacas, naturally infested with Trichostrongylus spp. and Oesophagostomum spp., were randomly divided into a treated and a control group, and injected with ivermectin subcutaneously at a dose rate of 0.2 mg/kg bodyweight. Faecal samples were collected per rectum immediately prior to treatment from each individual animal in the study, and every week thereafter for the next 5 weeks. Both for the llamas and the alpacas, there was a 100% reduction in faecal egg output during at least 3 weeks. None of the animals showed adverse reactions to the ivermectin treatment.

Efficacy of long-term monthly administration of ivermectin on the progress of naturally acquired heartworm infections in dogs

This study was designed to evaluate the efficacy of prolonged monthly ivermectin treatment against Dirofilaria immitis in client-owned dogs with naturally acquired infections and to clinically monitor the animal's response to the slow killing of heartworms, with death of the worms distributed over a period of up to 2 years. A total of 17 male and female dogs of different breeds and ages were used. Prior to treatment, all of the dogs tested positive for heartworm antigen (Ag) and all but two had microfilariae (mf). The dogs were randomly allocated to one group of seven dogs which received a commercial formulation of ivermectin (minimum, 6 mcg IVM/kg) plus pyrantel (minimum, 5 mg PP/kg) (Heartgard Plus™ Chewables, Merial, Ltd.), another group of seven dogs which received a commercial formulation of IVM (min, 6 mcg/kg) (Heartgard ® Chewables, Merial Ltd.), and a group of three dogs which served as an untreated controls. All dogs were evaluated prior to initiation of treatment and thereafter at 3- to 5-month-intervals for mf, Ag, and radiographic and echocardiographic findings. All of the 17 dogs, with the exception of two dogs in the IVM group, had circulating mf of D. immitis prior to the 1st monthly dose, and a few also had mf of Dirofilaria repens. After 4 monthly doses, only one dog in the IVM/PP group and two dogs in the IVM group had a patent heartworm infection, and no heartworm mf were seen in the 14 treated dogs thereafter. After 10 monthly doses, the number of Ag-positive dogs in both of the treated groups decreased gradually. Efficacy, based on the reduction in number of Ag-positive dogs, was similar for the IVM/PP and IVM groups, with overall efficacy scores for the 14 dogs of 21, 21, 43, and 71% after 10, 14, 19, and 24 monthly doses, respectively. Two of the seven dogs treated with IVM/PP, one of the seven treated with IVM, and two of the three untreated controls showed echocardiographic evidence of a parasitic burden prior to treatment, and all of these scores had decreased by the end of the study. Only one dog (IVM/PP group) had a cardiovascular pattern of heartworm disease by echocardiography prior to treatment, but this dog's score increased to two and the scores of two additional dogs increased from zero to two (IVM group) or three (IVM/PP group) by the end of the study. Only 1 (IVM/PP group) of the 17 dogs showed a pulmonary pattern of heartworm disease by radiography prior to treatment, but this dog's score increased to three by the end of the study. The radiographic scores of two additional dogs in the treated groups increased from zero to three (IVM/PP) or two (IVM) by the end of the study. Thus, monthly administration of IVM to dogs with clinical, radiographic or echocardiographic evidence of heartworm disease is ill-advised and such treatment of even the asymptomatic dog should be done only with much caution and frequent monitoring by the veterinarian.

In-feed 0.6% ivermectin formulation for treatment of wild boar in the Moslavina hunting ground in Croatia

An in-feed 0.6% ivermectin formulation was administered for 7 days to wild boar piglets at three sites of the Moslavina hunting ground in Croatia. Examination of internal organs and skin of five piglets that died immediately before the start of administration of the ivermectin formulation revealed the presence of Metastrongylus apri and Metastrongylus pudendotectus in the lungs, and of Ascarops strongylina, Physocephalus sexalatus and Globocephalus urosubulatusin in the gastrointestinal tract. Coccidial oocysts were found in the feces of all animals. Sarcoptes scabiei var. suis was identified in the skin of four piglets. The efficacy of treatment was assessed by examining fecal samples before start of therapy (day 0) and on days 7 and 14. Before treatment strongylid-type eggs were detected in 70–100% of fecal samples (210–505 EpG) The eggs of Strongyloides ransomi, Trichuris suis, Ascaris suum, Ascarops strongylina and Physocephalus sexalatus were identified in 10–50% of fecal samples at an intensity of 5–45 EpG. On day 14 after the start of the treatment, strongylid-type eggs were detected in 10% of fecal samples from one of the three sites only. Eggs of other helminth species were not detected at any of the three sites. This confirmed the successful therapeutic efficacy of the in-feed 0,6% ivermectin formulation.

Pharmacokinetic evaluation of four ivermectin generic formulations in calves

The plasma concentration profiles of four randomly chosen ivermectin (IVM) generic formulations (IVM G1–G4) were compared after their subcutaneous (SC) administration to healthy calves. The disposition of other avermectin-type endectocide compounds, doramectin (DRM) and abamectin (ABM), was also assessed in the same pharmacokinetic trial. Forty-two parasite-free Aberdeen Angus male calves were randomly allocated into six treatment groups. Animals in each group ( n=7) received SC treatment (200 μg/kg) with one of the commercially available endectocide formulation used in the trial. Blood samples were taken into heparinised vacutainer tubes from the jugular vein prior to and up to 35 days post-treatment. The recovered plasma was analysed by HPLC with fluorescence detection. Large kinetic differences were observed among the DRM, ABM and IVM formulations under evaluation. The DRM plasma concentration profiles were higher than those measured for ABM and all the IVM generic formulations. The higher and sustained plasma concentrations of DRM accounted for greater area under concentration–time curve (AUC) and longer mean residence time (MRT) values compared to those obtained for both ABM and the IVM generic preparations. The pattern of IVM absorption from the site of subcutaneous administration showed differences among the generic formulations under evaluation. The IVM G2 preparation showed higher peak plasma concentration and AUC values ( P<0.05) compared to those obtained after the administration of the IVM G1 formulation. Longer ( P<0.05) MRT values were obtained after the administration of the IVM G3 compared to other IVM generic preparations. The kinetic behaviour of ABM did not show significant differences with that described for most of the IVM formulations. This study demonstrates that major differences on drug kinetic behaviour may be observed when using different endectocide injectable formulations in cattle.

Efficacy of injectable and pour-on microdose ivermectin in the treatment of goat warble fly infestation by Przhevalskiana silenus (Diptera, Oestridae)

The prophylactic efficacy of microdoses of injectable and pour-on ivermectin formulations against larval stages of Przhevalskiana silenus was assessed in naturally infected goats in the region of Calabria (southern Italy). Sixty-eight goats from two goat farms were divided into five groups: one group remained untreated, while the other four groups were treated with microdoses of ivermectin (5 and 10 μg/kg injectable formulation and 10 and 20 μg/kg pour-on formulation). The microdoses of ivermectin were fully effective in the treatment of goat warble fly infestation (GWFI) as no larvae emerged from the warbles in the treated groups, while all the larvae emerged in the control groups. Irrespective of the type of formulation used, the difference between the treated groups and the control group was statistically significant ( P<0.001). By contrast, no statistical differences were found between the goats treated with the injectable formulation and those receiving the pour-on applications, and between the two doses of the injectable and pour-on formulations used. Given the plasma concentrations it attains at its lowest dose (0.052–0.042 ng/ml for the injectable formulation and 0.030 ng/ml for the pour-on) the injectable formulation seems to offer the most reliable route for the administration of ivermectin microdoses and it is acceptable for milk consumption. The introduction of ivermectin in the early eighties and the use of microdoses in some cases have made it possible to control cattle hypodermosis in large areas of Europe. As with cattle hypodermosis, the administration of ivermectin microdoses in goats is particularly interesting because of the low costs involved and the low levels of residues found in goat milk; it may thus constitute the basis for GWFI control campaigns in areas where the disease is prevalent.

Efficacy of injectable and pour-on microdose ivermectin in the treatment of goat warble fly infestation by Przhevalskiana silenus (Diptera, Oestridae)

The prophylactic efficacy of microdoses of injectable and pour-on ivermectin formulations against larval stages of Przhevalskiana silenus was assessed in naturally infected goats in the region of Calabria (southern Italy). Sixty-eight goats from two goat farms were divided into five groups: one group remained untreated, while the other four groups were treated with microdoses of ivermectin (5 and 10 μg/kg injectable formulation and 10 and 20 μg/kg pour-on formulation). The microdoses of ivermectin were fully effective in the treatment of goat warble fly infestation (GWFI) as no larvae emerged from the warbles in the treated groups, while all the larvae emerged in the control groups. Irrespective of the type of formulation used, the difference between the treated groups and the control group was statistically significant ( P <0.001). By contrast, no statistical differences were found between the goats treated with the injectable formulation and those receiving the pour-on applications, and between the two doses of the injectable and pour-on formulations used. Given the plasma concentrations it attains at its lowest dose (0.052–0.042 ng/ml for the injectable formulation and 0.030 ng/ml for the pour-on ) the injectable formulation seems to offer the most reliable route for the administration of ivermectin microdoses and it is acceptable for milk consumption. The introduction of ivermectin in the early eighties and the use of microdoses in some cases have made it possible to control cattle hypodermosis in large areas of Europe. As with cattle hypodermosis, the administration of ivermectin microdoses in goats is particularly interesting because of the low costs involved and the low levels of residues found in goat milk; it may thus constitute the basis for GWFI control campaigns in areas where the disease is prevalent.

Effects of ivermectin and doramectin faecal residues on the invertebrate colonization of cattle dung

Abstract: The effects of avermectin [ivermectin (IVM) and doramectin (DRM)] faecal residues on dung colonization and degradation by invertebrates were evaluated during late spring in the east of La Pampa province, Argentina. The study was conducted after collection of faecal material from animals (10 steers per group) allocated to the following groups: untreated control group (CG) and groups treated subcutaneously (200 μg/kg) with either DRM (DG) or a long‐acting formulation of IVM (IG). Fifty pats (550 g each) per group were collected, prepared and deposited on the field on days 3, 7, 16 and 29 post‐treatment (pt). Eight pats per group were recovered after 7, 14, 21, 42, 100 and 180 days post‐deposition (pd) on the field. The weight, percentage of dry matter, number of arthropods and nematodes from faeces were determined. The faecal concentrations of IVM and DRM were measured by high performance liquid chromatography (HPLC) throughout the trial period to correlate the pattern of drug degradation in dung with pd time. The total number of arthropods in dungs from CG was higher (P &lt; 0.05) than those counted between days 3 and 29 pt in IG and DG. A decrease in the number of Coleoptera larvae (P &lt; 0.05) between days 21 and 42 days pd was observed in both treated groups. Diptera larvae counts in CG pats were significantly higher (P &lt; 0.05) than those obtained in treated groups in the 7‐ and 14‐day‐old pats. A lower number (P &lt; 0.05) of Collembola, compared with pats from CG, was recovered from IG and DG pats deposited at days 3 and 7 pt and exposed from day 42. The counts of Acari in pats from treated animals were lower (P &lt; 0.05) than those observed in CG pats at 3, 8 and 16 days pt. There were no differences neither in adult Scarabaeidae recovered nor in the proportions of dung buried and destroyed by great dung beetles. Dung specific nematodes were reduced (P &lt; 0.05) in IG and DG pats from 3 and 7 days pt compared with those of CG pats. The comparative results shown here demonstrate that the negative effects of both IVM and DRM on dung colonization are similar. The pattern of drug degradation in the environment was very slow. High residual concentrations of both active parent compounds were recovered in dungs exposed in the field for up to 180 days pd. Concentrations as high as 13 ng/g (IVM) and 101 ng/g (DRM) were measured in faeces obtained from pats deposited on day 27 pt and exposed to the environment during 180 days. The results show a decrease in invertebrate colonization of dung recovered from IVM‐ and DRM‐treated cattle, which is in agreement with the large drug residual concentrations measured in faeces.

Pharmacokinetics of Doramectin and Ivermectin After Oral Administration in Horses*

A study was undertaken in order to compare plasma disposition kinetic parameters of doramectin (DRM) and ivermectin (IVM) in horses after oral administration. Ten crossbreed adult horses, clinically healthy, weighing 380–470kg body weight (bw) were selected for study. Faecal examinations were performed to determine faecal parasite egg counts. Horses were allocated to two groups of five animals to provide an even distribution considering the variables sex, body weight and faecal egg count. Group I, were treated with an oral paste formulation of IVM at 0.2mg/kg b/w and Group II, were treated with an oral dose of 0.2mg/kg bw of DRM prepared as paste from the injectable formulation for oral administration. Blood samples were collected by jugular puncture between 0h and 75 days post-treatment. Plasma was separated and later solid phase extraction and derivatization samples were analysed by high performance liquid chromatography (HPLC); a computerised kinetic analysis was carried out. Data were compared using the Mann–Whitney U-test.The mean plasma concentrations of DRM and IVM after oral administration in horses were detected until 30 and 20 days, respectively. Both drugs showed similar patterns of absorption and no significant differences were found for peak concentration, the time to peak concentration, or for absorptive half-life. The terminal elimination half-life was significantly (P<0.05) longer in the DRM treated group than for the IVM treated group. The differences observed in the elimination half-life explain the longer mean residence time and high values of area under the concentration time curve for the group treated with DRM, which are 30% higher than those of the IVM group. Considering its pharmacokinetics, tolerance and anthelmintic efficacy, the oral administration of DRM, could be an alternative to IVM for the control of parasitic diseases of horses.