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.     

Ivermectin in Senegalese Peulh Sheep: Influence of Sex on Plasma Disposition

The plasma disposition kinetics of ivermectin following a single subcutaneous administration of 0.2 mg/kg was investigated in male and female Senegalese Peulh sheep. Ten clinically healthy animals (5 males and 5 females) weighing 38–45 kg were used in this trial. Blood samples were collected by jugular puncture at different times between 0.5 h and 30 days post treatment. After plasma extraction and derivatization, samples were analysed by HPLC with fluorescence detection. Computerized kinetic analysis was carried out and mean parameters were statistically compared with the Mann–Whitney U-test. The area under the concentration–time curve (AUC) was significantly higher (p < 0.0027) in females than in males. Although the differences in maximum concentration (C _max), mean residence time (MRT) and half-life of elimination (t _1/2el) between males and females did not achieve statistical significance, values tended to be higher in females. Sex differences may be parallel with the level of storage in fat. Further investigations are required to improve the use of ivermectin in Senegalese sheep and findings may be used to predict optimal anthelmintic strategies for management of African species depending on the parasites present in a production system.     

大环内酯类抗寄生虫药耐药性研究进展

近年来,世界各国陆续报道了寄生虫对大环内酯类抗寄生虫药物的耐药性。影响这类药物耐药性产生和发展的因素很多,包括药物的结构、性质、药物选择压力、耐药基因的遗传特性、用药频率、用药时机、治疗效果以及用药剂量等。谷氨酸门控氯离子通道亚基构象的突变,是引起寄生虫对依赖其作用的药物产生耐药的主要原因。但是,这类药物的耐药机制比较复杂,还存在着γ-氨基丁酸门控氯离子通道受体结构改变引起的耐药以及P-糖蛋白基因结构改变引起的耐药。     

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 (C_max) and the time to reach C_max 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.