Injectable Formulations Of Ivermectin Research Articles

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.

Evaluation of generic injectable ivermectin for control of nematodiasis in feedlot heifers

Nematode parasitism of feedlot cattle has received very little research attention. It is assumed that anthelmintics administered at feedlot entry are effective and that feedlot conditions preclude post-treatment infection by helminths. Given the paucity of information about feedlot nematodiasis, the current research project was conducted. During October of 2010, 104 animals were selected at random from approximately 1600 beef heifers received at one feedlot in California and penned as a group. Of those, 96 were administered a generic, injectable formulation of ivermectin at label dose, while the remaining eight animals were left as untreated controls. Controls and eight randomly selected treated animals were necropsied for parasite quantifications at eight weeks post-treatment. At the end of the feeding period (approximately 135 days post-treatment), parasite quantifications were performed on nine animals selected at random from the remaining 88 animals. Fecal samples were periodically collected from cattle in the feedlot during the study. As evidenced by reductions in both fecal egg count and parasite quantifications at necropsy, a lack of drug efficacy was apparent for Cooperia and Ostertagia, and suspect for Haemonchus infections.

Comparative evaluation of two ivermectin injectable formulations against psoroptic mange in feedlot cattle

A study was carried out to compare the efficacy of two injectable formulations of ivermectin, Ivomec ®, 1 1 IVOMEC ® is a registered trademark of Merial in the United States of America and elsewhere. Merial (IVM reference) and Ivogell ®, 2 2 IVOGELL ® is a registered trademark of Intervet Productions S.r.l. Intervet (IVM generic) in the treatment of psoroptic mange ( Psoroptes ovis) in Charollais feedlot cattle. A total of 22 animals were ranked in order of the severity of mange and allocated to 11 replicates of 2 animals each. Within each replicate, one animal was randomly allocated to IVM reference product treatment (Group 1) and one to IVM generic (Group 2). Animals were treated on Day 0 and on Day 8 at the recommended dosage of 200 μg ivermectin/kg bodyweight. The pharmacokinetics profiles (p K) of both IVM formulations were evaluated in plasma samples taken from 6 cattle randomly chosen per group on Day 0, before treatment, and then at 6, 12, 24 hours and daily from Day 2 to Day 7 after the treatment on Day 0. Additionally, the severity of mange lesions was assessed and mites were counted in skin scrapings on Days 0, 8, 15 and 25. Animals were weighed on Day 0 and 25 and body weight and average daily gains (ADG) were evaluated. No statistical differences were found between the cattle of the two groups in any p K parameters, although the mean IVM plasma concentrations in cattle treated with the IVM reference product were consistently higher than those found in cattle treated with the generic compound. By Day 25, all animals in Group 1 had recovered clinically and parasitologically from psoroptic mange while cattle from Group 2 still had mange lesions and, in two animals, living mites were found in the skin scrapings; these differences were significant ( P < 0.001). The mean body weight of the two groups was significantly different on Day 25 ( P < 0.01) when animals in Group 1 weighed 20 kg more than those in Group 2. In conclusion, despite similarities in their pharmacokinetic profiles and formulations, the clinical efficacy of the two injectable formulations of IVM differed significantly in their therapeutic efficacy against psoroptic mange in feedlot cattle up to 25 days after treatment: this difference in response was reflected in an incomplete clinical and parasitological response in Group 2 and a slower growth rate.

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%.

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.

Transmission of Babesia spp by the cattle tick (Boophilus microplus) to cattle treated with injectable or pour-on formulations of ivermectin and moxidectin.

To assess the efficacy of ivermectin and moxidectin to prevent transmission of Babesia bovis and Babesia bigemina by Boophilus microplus to cattle under conditions of relatively intense experimental challenge. Naive Bos taurus calves were treated with either pour-on or injectable formulations of either ivermectin or moxidectin and then exposed to larvae of B microplus infected with B bovis or larvae or adults of B microplus infected with B bigemina. One calf was used for each combination of haemoparasite, B microplus life stage, drug and application route. Groups of calves were treated with the test drugs in either pour-on or injectable formulation and then infested with B microplus larvae infected with B bovis or B bigemina. B bigemina infected adult male ticks grown on an untreated calf were later transferred to a fourth group of animals. Infections were monitored via peripheral blood smears to determine haemoparasite transmission. Cattle treated with either pour-on or injectable formulations of ivermectin and moxidectin became infected with B bovis after infestation with infected larvae. Similarly, larvae infected with B bigemina survived to the nymphal stage to transmit the haemoparasite to animals treated with each drug preparation. Cattle treated with pour-on formulations of ivermectin and moxidectin then infested with adult male ticks infected with B bigemina did not become infected with B bigemina whereas those treated with the injectable formulations of ivermectin and moxidectin did show a parasitaemia. Injectable or pour-on formulations of ivermectin and moxidectin do not prevent transmission of Babesia to cattle by B microplus. Use of these drugs can therefore not be recommended as a primary means of protecting susceptible cattle from the risk of Babesia infection.

Effects of drug residues in the faeces of cattle treated with injectable formulations of ivermectin and moxidectin on larvae of the bush fly,Musca vetustissimaand the house fly,Musca domestica

To assess the toxicity of residues of ivermectin and moxidectin in cattle faeces collected at intervals after treatment. Replicated bioassays of faeces using larvae of the bush fly, Musca vetustissima and the house fly, Musca domestica. Two groups of five Murray Grey x Aberdeen Angus steers were treated with injectable formulations of ivermectin and moxidectin respectively. A third group was used as an untreated control. Newly emerged fly larvae were reared in the dung of treated animals. Drug residues in faeces collected 3 to 35 days after treatment with an injectable formulation of moxidectin had no significant effect on the survival of larvae of M vetustissima. Similarly, faeces dropped up to seven days after treatment caused no significant reduction in larval survival in M domestica. In day 2 dung, residues of moxidectin delayed development of M vetustissima larvae, but had no effect on their survival. In contrast, ivermectin-treated steers, produced dung that inhibited larval development of both M vetustissima and M domestica for 7 to 14 days after treatment. Significant reductions in survival of M vetustissima larvae occurred in dung collected on days 21 and 28 after treatment, but by day 35 survival did not differ from that in control dung. Excreted faecal residues of moxidectin are relatively innocuous to larvae of both M vetustissima and M domestica. Those of ivermectin inhibit survival for 7 to 14 days after treatment and are likely to have adverse effects on non-target organisms.

Inefficacy of moxidectin and doramectin against ivermectin-resistantCooperiaspp. of cattle in New Zealand

Two cases are described in which strains of Cooperia spp. of cattle were found to be resistant to either the oral or the injectable formulations of ivermectin. Injectable moxidectin was not effective against the latter strain and doramectin was not effective against either of the ivermectin-resistant Cooperia isolates. In both cases, the anthelmintic efficacy of oral levamisole was 100%.

Ivermectin resistant Haemonchus contortus in Louisiana lambs.

Fifteen weaned crossbred (Suffolk x Louisiana Native) lambs were treated with albendazole (10 mg kg-1) to remove existing nematode infections. They were inoculated with Haemonchus contortus infective larvae from a residual population surviving treatment with the oral formulation of ivermectin (0.2 mg kg-1). One group of five lambs remained untreated, another group of five was treated with the injectable formulation of ivermectin (0.2 mg kg-1), and a third group of five was treated with the oral formulation of ivermectin (0.2 mg kg-1). Subsequent to the treatments, there was essentially no difference in mean fecal egg count or mean number of H. contortus recovered at necropsy between the three groups.

Residual nematocidal effectiveness of ivermectin in cattle

Summary We assessed the duration of ivermectin persistence by measuring posttreatment nematocidal effectiveness; topical and injectable formulations of ivermectin were evaluated. Thirty-five nematode-free calves were randomly allocated to 1 of 5 treatment groups (7 calves/group). The treatment (Trt) group designations were: Trt 1, nonmedicated; Trt 2, injectable ivermectin administered at the rate of 0.2 mg/kg of body weight on day 0; Trt 3, injectable ivermectin administered at the aforementioned rate, but on day 7; Trt 4, topically administered ivermectin at the rate of 0.5 mg/kg on day 0; and Trt 5, topically administered ivermectin at the aforementioned rate, but on day 7. All calves were subsequently given infective larvae of Haemonchus, Cooperia, Trichostrongylus, and Oesophagostomum spp on day 21. One week later, each calf was additionally administered infective larvae of Dictyocaulus and Ostertagia spp. Trial calves were euthanatized on trial days 49 to 52 for nematode quantitation. On the basis of geometric mean comparisons, total nematode burdens were reduced from control group counts by 98.9 and 86.3% for calves treated on days 7 and 0 with injectable formulations, respectively, and 97.2 and 64.7% for calves treated on days 7 and 0 with pour-on formulations, respectively. Trichostrongylus colubriformis infections were most refractory to the persistent activity of ivermectin, with H placei also proving to be persistence limiting. All treatments were easily administered, and adverse behavioral or tissue reactions were not observed.

The efficacy and persistent anthelmintic effect of ivermectin in sheep

The direct efficacy and the long-term persistent anthelmintic effect of an oral suspension and an injectable formulation of ivermectin at a dose rate of 0.2 mg kg −1 was studied in sheep. Lambs were infected experimentally with Haemonchus contortus, Trichostrongylus vitrinus and Cooperia curticei. After 3 weeks they were treated with an oral suspension or with an injection, and reinfected with the same dose of larvae 3, 6 or 10 days after treatment. Post-mortem worm counts showed no persistent effect of the oral suspension. The injectable formulation showed an excellent persistent effect for up to 10 days against H. contortus. Reinfection with C. curticei 3 days after treatment resulted in a 64% reduction of the worm burden, but reinfection after 6 and 10 days was 100% reduced. The reduction of T. vitrinus was 46% after 3 days and 92% after 6 and 10 days.