Pharmacokinetics of extended-release ivermectin microspheres after oral administration to healthy pigs

We compared the pharmacokinetics of ivermectin premix and ivermectin microspheres in pigs after single and multiple administration regimes. In the single-dose experiments, 24 piglets were randomly divided into three groups and given ivermectin at 0.3 mg/kg using (a) 1.0% ivermectin administered subcutaneously, (b) 0.25% ivermectin premix orally, and (c) 0.25% ivermectin microspheres orally. In the multiple-dose experiment, 6 pigs in two equal groups received ivermectin premix and microspheres orally at 0.3 mg/kg for 7 consecutive days to monitor the valley plasma levels. The plasma samples were detected by fluorescence high-performance liquid chromatography, and concentration–time data were fitted to a noncompartmental model. After oral administration of ivermectin microspheres at a single dose, the elimination rate constant (Kel), the half-life (t_1/2), the peak time (T_max), the mean residence time (MRT), and the peak concentration (C_max) were 0.012 ± 0.0031/hr, 59.94 ± 20.18 hr, 9.50 ± 0.93 hr, 55.96 ± 11.40 hr, and 37.75 ± 3.45 ng/ml, respectively. The C_max of microspheres was not statistically different (p > .05) compared with that of premix groups (39.81 ± 5.83 ng/ml). Moreover, the AUC of the microcapsule groups was increased from 1,129.76 ± 245.62 to 1,607.33 ± 343.35 hr ng/ml compared with the premix groups, and the relative bioavailability increased by an average of 17.53% after oral administration with ivermectin microspheres. Multiple-dose administration also indicated pigs fed with ivermectin microspheres can get a higher minimum steady-state concentration and a longer maintenance time than ivermectin premix.     

盐酸多西环素在猪体内的药物动力学及其残留

试验建立了反相高效液相色谱(RT-HPLC)法测定盐酸多西环素的浓度,探讨了盐酸多西环素在猪体内的药物动力学和残留特征。结果表明,盐酸多西环素以2.5mg/kg单剂量肌内注射给猪(n=6),药物动力学模型符合有吸收一室模型,药物动力学参数:吸收半衰期(t1/2ka)、消除半衰期(t1/2ke)为(0.400±0.312)h、(9.530±0.956)h,药时曲线下面积(AUC)为(44.414±4.123)mg·h·L-1,最大血药浓度(Cmax)为(2.811±0.136)mg/L,达峰时间(Tp)为(1.910±0.213)h。另外,以相同剂量肌内注射给猪(n=6),每天1次,连续给药4d后,在不同时间测定盐酸多西环素在猪的肌肉、肝脏、肾脏、皮肤和脂肪中的残留量。在给药后16d,盐酸多西环素在各组织均能检测到,且残留均低于残留限量。盐酸多西环素注射液在猪体内消除缓慢,残留期较长,建议休药期不低于16d。     

Assessment of the long‐acting ivermectin formulation in sheep: Further insight into potential pharmacokinetic interactions

The aim of the current study was to evaluate the in vivo pharmacokinetic of ivermectin (IVM) after the administration of a long‐acting (LA) formulation to sheep and its impact on potential drug‐drug interactions. The work included the evaluation of the comparative plasma profiles of IVM administered at a single therapeutic dose (200 μg/kg) and as LA formulation at 630 μg/kg. Additionally, IVM was measured in different gastrointestinal tissues at 15 days posttreatment with both IVM formulations. The impact of the long‐lasting and enhanced IVM exposure on the disposition kinetics of abamectin (ABM) was also assessed. Plasma (IVM and ABM) and gastrointestinal (IVM) concentrations were analyzed by HPLC with fluorescent detection. In plasma, the calculated C_max and AUC_0‐t values of the IVM‐LA formulation were 1.47‐ and 3.35‐fold higher compared with IVM 1% formulation, respectively. The T_1/2ab and T_max collected after administration of the LA formulation were 2‐ and 3.5‐fold longer than those observed after administration of IVM 1% formulation, respectively. Significantly higher IVM concentrations were measured in the intestine mucosal tissues and luminal contents with the LA formulation, and in the liver, the increase was 7‐fold higher than conventional formulation. There was no drug interaction between IVM and ABM after the single administration of ABM at 15 days post‐administration of the IVM LA formulation. The characterization of the kinetic behavior of the LA formulation to sheep and its potential influence on drug‐drug interactions is a further contribution to the field.     

Pharmacokinetics of ivermectin in sheep following pretreatment with Escherichia coli endotoxin

The comparative pharmacokinetics of ivermectin (IVM), between healthy and in Escherichia coli lipopolysaccharides (LPS) injected sheep, was investigated after an intravenous (IV) administration of a single dose of 0.2 mg/kg. Ten Suffolk Down sheep, 55 ± 3.3 kg, were distributed in two experimental groups: Group 1 (LPS): treated with three doses of 1 μg LPS/kg bw at ?24, ?16, and ?0.75 hr before IVM; group 2 (Control): treated with saline solution (SS). An IV dose of 0.2 mg IVM/kg was administered 45 min after the last injection of LPS or SS. Plasma concentrations of IVM were determined by liquid chromatography. Pharmacokinetic parameters were calculated based on non‐compartmental modeling. In healthy sheep, the values of the pharmacokinetic parameters were as follows: elimination half‐life (2.85 days), mean residence time (MRT) (2.27 days), area under the plasma concentration curve over time (AUC, 117.4 ng day^?1 ml^?1), volume of distribution (875.6 ml/kg), and clearance (187.1 ml/day). No statistically significant differences were observed when compared with the results obtained from the group of sheep treated with LPS. It is concluded that the acute inflammatory response (AIR) induced by the intravenous administration of E. coli LPS in adult sheep produced no changes in plasma concentrations or in the pharmacokinetic behavior of IVM, when it is administered intravenously at therapeutic doses.     

Biovailability of ivermectin administered orally to dogs

The bioavailability of three formulations of ivermectin was determined following oral administration to dogs. The average peak plasma level (C _max) of ivermectin administered in the standard tablet formulation at 6 and 100 µg/kg of body weight was 2.97 and 44.31 ng/g, respectively. This suggest dose-dependent pharmacokinetics.C _max and total ivermectin bioavailability, as assessed from the area under the plasma curve (AUC), were similar between two tablet formulations of ivermectin administered at 100 µg/kg. Furthermore,C _max was similar following administration of radiolabelled ivermectin at 6 µg/kg in either a beef-based chewable formulation or in the standard tablet formulation.     

伊维菌素在樱桃谷鸭体内证治药物动力学研究

本试验利用证治药动学的方法,研究了伊维菌素在樱桃谷鸭体内药物动力学变化,旨在验证黄曲霉毒素B1中毒后中药制剂＂保肝护肾脱霉素＂的药理作用。将117只健康1日龄的樱桃谷鸭随机平均分成3组,Ⅰ组（正常组）饲喂健康饲料,饲喂28d。Ⅱ组（病理组）前7d饲喂健康饲料,8-21d饲喂含有黄曲霉毒素B1的霉变饲料,22-28d饲喂健康饲料。Ⅲ组（中药反证组）前7d饲喂健康饲料,8-22d饲喂含黄曲霉毒素B1的霉变饲料,22-28d饲喂健康饲料,与此同时对每只鸭子每天口服保肝护肾脱毒素液5mL,口服7d,第29天,给上述3组试验鸭口服伊维菌素溶液,分别在给药前（0h）和给药后时间点从鸭的颈静脉采血,采用高效液相荧光色谱法进行检测。结果显示,黄曲霉毒素B1造成的病理损伤,能改变伊维菌素内服在鸭体内的药动学特征,表现出吸收减慢,吸收程度减弱,消除速率减弱的药动学特征。经过中药制剂＂保肝护肾脱霉素＂反证后,伊维菌素的吸收及消除速度都有不同程度地增加。试验结果表明,从药动学角度说明中药制剂＂保肝护肾脱霉素＂对黄曲霉毒素B1造成的病理损伤有修复作用。     

Investigation of pharmacokinetic interaction between ivermectin and praziquantel after oral administration in healthy dogs

The purpose of this study was to determine the pharmacokinetic interaction between ivermectin (0.4 mg/kg) and praziquantel (10 mg/kg) administered either alone or co‐administered to dogs after oral treatment. Twelve healthy cross‐bred dogs (weighing 18–21 kg, aged 1–3 years) were allocated randomly into two groups of six dogs (four females, two males) each. In first group, the tablet forms of praziquantel and ivermectin were administered using a crossover design with a 15‐day washout period, respectively. Second group received tablet form of ivermectin plus praziquantel. The plasma concentrations of ivermectin and praziquantel were determined by high‐performance liquid chromatography using a fluorescence and ultraviolet detector, respectively. The pharmacokinetic parameters of ivermectin following oral alone‐administration were as follows: elimination half‐life (t_1/2λz) 110 ± 11.06 hr, area under the plasma concentration–time curve (AUC_0–∞) 7,805 ± 1,768 hr^.ng/ml, maximum concentration (C_max) 137 ± 48.09 ng/ml, and time to reach C_max (T_max) 14.0 ± 4.90 hr. The pharmacokinetic parameters of praziquantel following oral alone‐administration were as follows: t_1/2λz 7.39 ± 3.86 hr, AUC_0–∞ 4,301 ± 1,253 hr^.ng/ml, C_max 897 ± 245 ng/ml, and T_max 5.33 ± 0.82 hr. The pharmacokinetics of ivermectin and praziquantel were not changed, except T_max of praziquantel in the combined group. In conclusion, the combined formulation of ivermectin and praziquantel can be preferred in the treatment and prevention of diseases caused by susceptible parasites in dogs because no pharmacokinetic interaction was determined between them.     

A comparison of some of the pharmacokinetic parameters of three commercial sulphadiazine/trimethoprim combined preparations given orally to pigs

Three sulphadiazine/trimethoprim preparations were administered orally during feeding to pigs. Six male and six female pigs were used. Clinically important pharmacokinetic parameters of the two drugs in the three preparations were determined and compared.The plasma concentrations of sulphadiazine and trimethoprim increased rapidly in the pigs followed by a quite rapid decrease from 4 to 12 h after oral administration. The mean values of the absorption half-lives of sulphadiazine and trimethoprim were 0.9–1.6 h and 0.5–0.8 h, respectively. The corresponding values for the elimination half-lives of sulphadiazine and trimethoprim were 3.1–4.3 h and 3.4–6.0 h, respectively. There were no significant differences between the pharmacokinetic parameters of the two compounds in the three preparations with the exception of T_max for sulphadiazine and t_1/2 for trimethoprim. Comparative bioavailability calculations showed no statistically significant differences between sulphadiazine and trimethoprim in the three preparations.The weight increase of the pigs during the experimental period (mean = 37.3–64.9 kg) did not cause differences in the kinetics of the two drugs which could have consequences for the use of the three combined preparations in clinical practice.No unacceptable or antibacterial residues of sulphadiazine or trimethoprim were found in the kidneys of pigs slaughtered at 5, 7 and 10 days after administration.     

Pharmacokinetics of carprofen in anaesthetized pigs: a preliminary study

ObjectiveTo investigate the pharmacokinetics of carprofen after a single intravenous (IV) dose and multiple oral doses administered to pigs undergoing electroporation of the pancreas.Study designProspective experimental study.AnimalsA group of eight female pigs weighing 31.74 ± 2.24 kg (mean ± standard deviation).MethodsCarprofen 4 mg kg^?1 was administered IV after placement of a central venous catheter during general anaesthesia with isoflurane. Blood samples were collected 30 seconds before and 5, 10, 20, 30 and 60 minutes and 2, 4, 6, 8, 12 and 24 hours after carprofen administration. Subsequently, the same dose of carprofen was administered orally, daily, for 6 consecutive days and blood collected at 36, 48, 60, 72, 96, 120, 144 and 168 hours after initial carprofen administration. Plasma was analysed using liquid chromatography with mass spectrometry. Standard pharmacokinetic parameters were calculated by compartmental analysis of plasma concentration–time curves. Data are presented as mean ± standard error.ResultsThe initial plasma concentration of IV carprofen was estimated at 54.57 ± 3.92 μg mL^?1 and decreased to 8.26 ± 1.07 μg mL^?1 24 hours later. The plasma elimination curve showed a bi-exponential decline: a rapid distribution phase with a distribution half-life of 0.21 ± 0.03 hours and a slower elimination phase with an elimination half-life of 17.31 ± 3.78 hours. The calculated pharmacokinetic parameters were as follows: the area under the plasma concentration–time curve was 357.3 ± 16.73 μg mL^?1 hour, volume of distribution was 0.28 ± 0.07 L kg^?1 and plasma clearance rate was 0.19 ± 0.009 mL minute^?1 kg^?1. The plasma concentration of carprofen, administered orally from days 2 to 7, varied from 9.03 ± 1.87 to 11.49 ± 2.15 μg mL^?1.Conclusions and clinical relevanceCarprofen can be regarded as a long-acting non-steroidal anti-inflammatory drug in pigs.     

伊维菌素药动学研究进展

综述了伊维菌素在动物体内的吸收、分布、代谢、排泄过程以及其药代动力学研究进展,以期为伊维菌素的临床用药和新兽药开发提供依据。     

氟苯尼考在猪的群体药动学

收集临床消化道和呼吸道细菌性疾病猪 2 15头 ,其中原种猪 91头 ,杂交商品猪 12 4头 ;公猪 112头 ,母猪 10 3头 ;体重范围 5～ 4 1kg,平均为 18.6 8± 0 .4 7;日龄 6 3～ 117天 ,平均为 85 .2 4± 0 .78。动物随机分为两组 ,第 1组动物数量为总体数量的 2 / 3,共 14 6头 ,为模型组 ,用于建立群体药动学模型 ;第 2组动物数量为总体动物数量的 1/ 3,共 6 9头 ,为验证组。给药前测定每头猪血清生化指标。试验猪颈部肌肉注射 30 %氟苯尼考注射液 ,剂量为 2 0 mg· kg- 1体重。给药前采一次空白血浆及血清 (测定血清生化指标 ) ,给药后随机采样 ,每只猪采样 2～ 4次 ,就整个群体而言使采样时间均匀分布于药物的吸收相、分布相和消除相内 ,采样时间为给药后 0 .183～ 4 8.36 7h,以高效液相色谱法测定血浆药物浓度 ,应用 NONMEM程序处理所收集的数据 ,包括药时数据、猪只的体重、日龄、性别、种属及血清生化指标、对研究组数据拟合发现最佳药动学模型为一级吸收一室模型 ,药动学参数随机效应及自身变异的最佳模型均为对数加法模型。体重对机体清除率、表观分布容积有显著影响 ,机体清除率、表观分布容积随体重的增加而增加 ,基本呈线性关系。种属对吸收速率常数有显著影响。把研究组得到的群体药动学参数值应用     

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.     

那西肽对生长肥育猪的作用效果及其在产品中的残留

选择32头30kg左右健康的二元杂交生长猪, 随机分为4组, 每组8头, 个体饲喂, 4组均喂相同的基础饲粮, 但添加不同饲用抗生素,分别是低、高剂量那西肽(10mg/kg、50mg/kg)、盐霉素(30mg/kg) 和对照。猪体重达90kg时, 分别按0、3和7d停药后屠宰, 检测那西肽在样品各器官中的残留量。结果表明: 那西肽可显著提高生长肥育猪的采食量和日增重(P<0 05), 但是对料重比的改善作用不明显; 当检测灵敏度为0 01mg/kg时, 在低、高剂量那西肽组猪的心脏、肝脏、肾脏和背最长肌中, 均未检出那西肽。     

两种伊维菌素注射液在家兔体内的生物等效性研究

为评价两种伊维菌素注射液在家兔体内的生物等效性,采用双周期交叉给药方式,将16只健康家兔随机分成2组,按5 mg/kg体重皮下单剂量注射两种伊维菌素注射液,使用HPLC法测定血浆中的伊维菌素,利用3P97药动软件计算主要药动学参数。结果显示,受试制剂和参比制剂的T_(max)分别为(26.45±8.62)h,(22.33±11.72)h;Cmax分别为(182.73±59.27)ng/m L,(166.77±65.25)ng/m L;AUC_(0-t)分别为(21122±9999)ng·h·L~(-1),(19475±7009)ng·h·L~(-1);AUC_(0-∞)分别为(27390±12197)ng·h·L~(-1),(31559±13412)ng·h·L~(-1)。伊维菌素注射液受试制剂与参比制剂的AUC0-t、AUC0-∞、Cmax、Tmax均无显著性差异(P0.05),双单侧t检验结果显示两种制剂生物等效,可为兽医临床给药方案的制定以及合理用药提供参考。     

The influence of age on the pharmacokinetics of aditoprim in pigs after intravenous and oral administration

Some pharmacokinetic parameters of aditoprim were determined in 3- and 6-month-old pigs. After intravenous administration of 5 mg/kg body weight, the mean total body clearance of the older pigs was smaller than that of the younger pigs. This difference was not reflected in the elimination half-life. After oral administration of 5 mg/kg body weight, the mean absorption rate constant was smaller and the mean absorption half-life was longer in the older pigs. The age-related changes in the pharmacokinetics of aditoprim were not sufficiently pronounced to suggest the necessity of modifying the oral dosage regimen in pigs of this age range. The favourable pharmacokinetics of aditoprim in pigs (large apparent volume of distribution, long elimination half-life and high bioavailability) may permit introduction of this drug into swine practice, after safety and residue depletion studies.     

Daily ivermectin for treatment of generalized demodicosis in dogs

Abstract Twelve dogs with generalized demodicosis were treated with oral administration of ivermectin, 0.4 mg kg^-1 of body weight given once every 24 h. Results of skin scrapings were used to determine whether administration of ivermectin should be continued or stopped. Dogs that were free of clinical signs of demodicosis 12 months after administration of ivermectin was discontinued were considered cured. Five dogs were cured. The medían duration of treatment was 15 weeks (range 5–21 weeks). Seven dogs were failures, with five relapsing 3–11. 5 months after treatment was stopped, and two having persistent demodicosis in spite of treatment. Mild ivermectin toxicosis developed in one dog after 5 weeks of treatment; side-effects resolved shortly after the treatment was stopped. Resumen Se trataron doce perros con demodicosis generalizada con ivermectina oral, 0.4 mg/Kg de peso corporal una vez cada 24 h. Se realizaron raspados cutáneos para déterminar si debia retirarse o continuar con la administración de ivermectina. Se consideraron curados aquellos perros sin sintomatologia de demodicosis 12 meses después de retirar la terapia con ivermectina. La duración medía del tratamiento con ivermectina fue de 15 semanas (rango de 5–21). Se fracasó en siete perros, con cinco recidivas a los 3–11, 5 meses después de parar la terapia y dos con demodicosis persistente a pesar del tratamiento. Un perro desarrolló una toxicosis leve a la ivermectina a las 5 semanas del tratamiento; los efectos secundarios desaparecieron al poco de retirar el tratamiento. [Medleau, L., Ristic, Z., McElveen, D.R. Daily ivermectin for treatment of generalized demodicosis in dogs (Administración díaria de ivermectina para el tratamiento de le demodicosis generalizada en el perro). Veterinary Dermatology 1996; 7 : 209–212.] Résumé Douze chiens présentant une démodécie généralisée fürent traités par administration orale d'ivermectine à la dose de 0.4 mg/kg de poids une fois par jour. Les résultats des raclages cutanés servirent à déterminar la nécessité de continuer ou d'arrêter l'administration d'ivermectine. Les chiens ne présentant aucun symptôme de démodécie 12 mois après l'arrêt de l'ivermectine fürent considérés guéris. Cinq chiens fürent guéris. La durée moyenne du traitement fut de 15 semaines (intervalles de 5 à 21 semaines. Sept cas fürent des échecs, avec 5 chiens récidivant 3 à 11, 5 mois après l'arrêt du traitement, et 2 présentant une démodécie persistante malgré le traitement. Un chien a développé une intoxication modéree après 5 semaines de traitement; les effets secondaires disparaissant rapidement après l'arrêt du traitement. [Medleau, L., Ristic, Z., McElveen, D.R. Daily ivermectin for treatment of generalized demodicosis in dogs (Administration quotidienne d'ivermectine dans le traitement de la démodécie généralisée chez le chien). Veterinary Dermatology 1996; 7 : 209–212.] Zusammenfassung Zwölf Hunde mit generalisierter Demodikose wurden mit einer oralen Verabreichung von Ivermectin in der Dosierung von 0, 4 mg/kg Körpergewicht einmal alle 24 Stunden behandelt. Die Ergebnisse der Hautgeschabsel dienten zur Bestimmung, ob die Verabreichung weiterhin erfolgen sollte oder abzubrechen sei. Hunde, die 12 Monate nach Ende der Ivermectin-Verabreichung frei von klinischen Symptomen der Demodikose waren, wurden als geheilt betrachtet. Fünf Hunde waren geheilt. Die mittlere Therapiedauer betrug 15 Wochen (Spannweite 5 bis 21 Wochen). Bei sieben Hunden versagte die Therapie, wobei fünf nach 3 bis 11, 5 Monaten nach Behandlungsende ein Rezidiv bekamen und zwei Tiere trotz der Therapie einer persistierende Demodikose zeigten. Bel einem Hund entwickelte sich 5 Wochen nach der Behandlung eine milde Ivermectin-Intoxikation; die Nebenwirkungen verschwanden kurz nach Abbruch der Therapie. [Medleau, L., Ristic, Z., McElveen, D.R. Daily ivermectin for treatment of generalized demodicosis in dogs (Tägliche Ivermectinverabreichung als Behandlung für Hunde mit generalisierter Demodikose). Veterinary Dermatology 1996; 7 : 209–212.]     

Pharmacokinetics of hexobarbital, sulphadimidine and chloramphencoliin neonatal and young pigs.

Half-life and apparent specific volume of distribution of hexobarbital, sulphadimidine and chloramphenicol were investigated in newborn, 1, 3, 5 and 8 weeks old pigs. Hexobarbital sleeping time and plasma concentration of hexobarbital at recovery were measured in the same age groups. The half-life of hexobarbital and chloramphenicol was long in newborn pigs but decreased fast during the first week after birth. From 1 to 8 weeks after birth the decrease was less pronounced. The half-life of sulphadimidine increased during the first 3 weeks of life, but in 1 and 3 weeks old pigs the amount of N⁴-acetylated sulphadimidine in plasma at 200 min. after the injection was higher than in the newborn pigs.The apparent specific volume of distribution of hexobarbital, sulphadimidine and chloramphenicol was changed in different ways from birth to 8 weeks of age.The hexobarbital sleeping time was very long in the newborn pigs and decreased until 3 weeks of age. The concentration of hexobarbital in plasma at recovery was unchanged from birth to 8 weeks of age.The concentration of chloramphenicol metabolites in plasma 100 min. after the injection increased very fast during the 8 weeks of observation. The concentration of N⁴-acetylated sulphadimidine in plasma at 200 min. after the injection increased from birth to 1 week of age, then it decreased.The data are stressing that the neonatal pig is a convenient model for pharmacokinetic testing of drugs used as pharmacotherapeutics in neonatal life.     

高效液相色谱法测定赛鸽用复方吡喹酮胶囊中吡喹酮和伊维菌素的含量

用高效液相色谱法同时测定赛鸽用复方吡喹酮胶囊中吡喹酮和伊维菌素的含量.采用Nova-Pak C18柱(150 mm×3.9 mm,4 μm),以乙腈-甲醇-水(53:35:12)为流动相,流速为1.0 mL/min,检测波长254 nm,柱温25℃.在此色谱条件下,吡喹酮和伊维菌素的分离良好,吡喹酮和伊维菌素分别在511～1 534μg/mL和10.1～30.6μg/mL浓度范围内峰面积与浓度呈良好的线性关系(r＞0.999).按外标法以峰面积计算进行测定,吡喹酮和伊维菌素的平均回收率分别为99.9%和98.3%,RSD分别为0.3%和0.6%(n=9).本方法简便、快速、准确,适用于赛鸽用复方吡喹酮胶囊中吡喹酮和伊维菌素含量的测定.     

RP-HPLC检测复方注射剂中伊维菌素和吡喹酮的含量

为了用高效液相色谱法同时测定复方注射剂中伊维菌素和吡喹酮的含量。采用Hyper-C lone 5u C18柱（250 mm×4.60 mm,5μm）,以乙腈-甲醇-水（53∶35∶12）为流动相,流速为1.0mL/m in,检测波长254 nm,柱温30℃的液相检测方法。结果表明,在此色谱条件下,吡喹酮和伊维菌素的分离良好,吡喹酮和伊维菌素分别在30~500μg/mL和5~40μg/mL浓度范围内峰面积与浓度呈良好的线性关系（r2〉0.99）。按外标法以峰面积计算进行测定,吡喹酮和伊维菌素的平均回收率分别为98.93%和95.89%,RSD分别为0.33%和1.58%（n=9）。说明该方法简便、快速、准确,适用于复方吡喹酮注射液中吡喹酮和伊维菌素含量的测定。     

Pharmacokinetics and relative bioavailability of meloxicam oil suspension in pigs after intramuscular administration

This study aimed to develop one novel meloxicam (MEL) oil suspension for sustained-release and compare the pharmacokinetic characteristics of it with MEL conventional formulation in pigs after a single intramuscular administration. Six healthy pigs were used for the study by a crossover design in two periods with a withdrawal interval of 14 days. Plasma concentrations of MEL were measured by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Pharmacokinetic parameters were calculated by noncompartmental methods. The difference was statistically significant (p < .05) between MEL oil suspension and MEL conventional formulation in pharmacokinetic parameters of mean residence time (6.16 ± 4.04) hr versus (2.66 ± 0.55) hr, peak plasma concentration (C_max) (0.82 ± 0.12) µg/ml versus (1.12 ± 0.22) µg/ml, time needed to reach C_max (T_max) (2.33 ± 0.82) hr versus (0.59 ± 0.18) hr, and terminal elimination half-life (t_1/2λz) (3.74 ± 2.66) hr versus (1.55 ± 0.37) hr. The mean area under the concentration–time curve (AUC_0–∝) of MEL oil suspension and MEL conventional formulation was 5.35 and 3.43 hr µg/ml, respectively, with a relative bioavailability of 155.98%. Results of the present study demonstrated that the MEL oil suspension could prolong the effective time of drugs in blood, thereby reducing the frequency of administration on a course of treatment. Therefore, the novel MEL oil suspension seems to be of great value in veterinary clinical application.