Pharmacokinetics of levamisole in the red‐eared slider turtles (Trachemys scripta elegans)

The pharmacokinetics and bioavailability of levamisole were determined in red‐eared slider turtles after single intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration. Nine turtles received levamisole (10 mg/kg) by each route in a three‐way crossover design with a washout period of 30 days. Blood samples were collected at time 0 (pretreatment), and at 0.25, 0.5, 1, 1.5, 3, 6, 9, 12, 18, 24, 36, and 48 hr after drug administration. Plasma levamisole concentrations were determined by a high‐performance liquid chromatography assay. Data were analyzed by noncompartmental methods. The mean elimination half‐life was 5.00, 7.88, and 9.43 hr for IV, IM, and SC routes, respectively. The total clearance and volume of distribution at steady state for the IV route were 0.14 L hr^?1 kg^?1 and 0.81 L/kg, respectively. For the IM and SC routes, the peak plasma concentration was 9.63 and 10.51 μg/ml, respectively, with 0.5 hr of T_max. The bioavailability was 93.03 and 115.25% for the IM and SC routes, respectively. The IM and SC route of levamisole, which showed the high bioavailability and long t_1/2?z, can be recommended as an effective way for treating nematodes in turtles.     

Application of different pharmacokinetic models to describe and predict pharmacokinetics of voriconazole in magellanic penguins following oral administration

Aspergillosis is a condition causing serious morbidity and mortality in captive penguins and other bird species. It can be treated with antifungal drugs, such as voriconazole. However, the pharmacokinetics of voriconazole are variable between different animal and bird species. Therefore, the pharmacokinetics of voriconazole were investigated in this study in Magellanic penguins. Pharmacokinetic models were constructed and applied to predict the pharmacokinetics of voriconazole during long‐term treatment in Magellanic penguins, since the voriconazole treatment duration in chronic aspergillosis cases can last up to several months. Plasma voriconazole concentration–time data from adult Magellanic penguins (Spheniscus magellanicus; n = 15) following a single oral (PO) dose of either 2.5 mg/kg or 5 mg/kg in a herring in three separate study periods 7–12 months apart were collected. Mean plasma voriconazole concentrations were above the targeted MIC for Aspergillus fumigatus for 2 hr following a single 2.5 mg/kg voriconazole dose while the plasma concentrations exceeded the MIC for least 24 hr following a 5 mg/kg dose. Nonlinear mixed‐effects modeling was used to fit two pharmacokinetic models, one with first‐order and another with saturable elimination, to the single‐dose data. Fits were good for both, as long as dose was included as a covariate for the first‐order model so that clearance was lower and the half‐life longer for animals receiving the 5 mg/kg dose. Although the single‐dose data suggested saturated elimination at higher concentrations, the model with saturable elimination did not predict plasma voriconazole concentrations well for a clinical aspergillosis case receiving long‐term treatment, possibly because of induction of metabolizing enzymes with chronic exposure. Pharmacokinetic models should accurately predict plasma drug concentrations for different dosage regimens in order to be applicable in the field. Future studies should focus on determining clearance at steady‐state to be able to refine the pharmacokinetic models presented here and improve model performance for long‐term oral voriconazole administration in Magellanic penguins.     

Pharmacokinetics of florfenicol and thiamphenicol in ducks

The pharmacokinetics of florfenicol (FF) and thiamphenicol (TP) after single intravenous (IV) and oral (PO) administration was investigated in Mulard ducks. Both antibiotics were administered at a dose of 30 mg/kg body weight, and their concentrations in plasma samples were assayed using high‐performance liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were calculated using a noncompartmental method. After IV administration, significant differences were found for the mean residence time (2.25 ± 0.21 hr vs. 2.83 ± 0.50 hr for FF and TP, respectively) and the general half‐life (1.56 ± 0.15 hr vs. 1.96 ± 0.35 hr for FF and TP, respectively) indicating slightly slower elimination of TP as compared to FF. The clearance, however, was comparable (0.30 ± 0.07 L/hr/kg for FF and 0.26 ± 0.04 L/hr/kg for TP). The mean volume of distribution was below 0.7 L/kg for both drugs. Pharmacokinetics after PO administration was very similar for FF and TP suggesting minor clinical importance of the differences found in the IV study. Both antimicrobials showed rapid absorption and bioavailability of more than 70% indicating that PO route should be an efficient method of FF and TP administration to ducks under field conditions.     

Pharmacokinetics of sanguinarine,chelerythrine, and their metabolites in broiler chickens following oral and intravenous administration

Sanguinarine (SA) and chelerythrine (CHE) are the main active components of the phytogenic livestock feed additive, Sangrovit®. However, little information is available on the pharmacokinetics of Sangrovit® in poultry. The goal of this work was to study the pharmacokinetics of SA, CHE, and their metabolites, dihydrosanguinarine (DHSA) and dihydrochelerythrine (DHCHE), in 10 healthy female broiler chickens following oral (p.o.) administration of Sangrovit® and intravenous (i.v.) administration of a mixture of SA and CHE. The plasma samples were processed using two different simple protein precipitation methods because the parent drugs and metabolites are stable under different pH conditions. The absorption and metabolism of SA following p.o. administration were fast, with half‐life (t_1/2) values of 1.05 ± 0.18 hr and 0.83 ± 0.10 hr for SA and DHSA, respectively. The maximum concentration (C_max) of DHSA (2.49 ± 1.4 μg/L) was higher that of SA (1.89 ± 0.8 μg/L). The area under the concentration vs. time curve (AUC) values for SA and DHSA were 9.92 ± 5.4 and 6.08 ± 3.49 ng/ml hr, respectively. Following i.v. administration, the clearance (CL) of SA was 6.79 ± 0.63 (L·h^?1·kg^?1) with a t_1/2 of 0.34 ± 0.13 hr. The AUC values for DHSA and DHCHE were 7.48 ± 1.05 and 0.52 ± 0.09 (ng/ml hr), respectively. These data suggested that Sangrovit® had low absorption and bioavailability in broiler chickens. The work reported here provides useful information on the pharmacokinetic behavior of Sangrovit® after p.o. and i.v. administration in broiler chickens, which is important for the evaluation of its use in poultry.     

牛蒡苷元在仔猪体内的药物动力学研究

为研究牛蒡苷元在仔猪体内的药物动力学特征,了解其在仔猪体内的吸收、分布、转化和排泄规律,为新兽药的研发和临床用药提供理论参考依据。选取健康仔猪8头(30.0±5.0 kg),以2.0 mg/kg.bw的牛蒡苷元静脉注射给药,不同时间点前腔静脉采血,采用HPLC法对猪血浆中牛蒡苷元的浓度进行分析。牛蒡苷元静脉注射后,符合无吸收二室模型,主要药动学参数为：分布半衰期(t1/2α)0.166±0.022 h;消除半衰期(t1/2β)3.161±0.296 h;表观分布容积(Vd)0.231±0.033 L/kg;清除率(CLb)0.057±0.003 L/(h·kg);药时曲线下面积(AUC)1.189±0.057 μg·h·mL-1。由此可知,牛蒡苷元静脉注射后在仔猪体内分布迅速、分布组织较少、代谢消除较快。     

Pharmacokinetics of meloxicam in adult goats: a comparative study of subcutaneous,oral and intravenous administration

AIMS: To determine the plasma disposition of meloxicam in goats following S/C, oral or I/V administration at a single dose of 0.5?mg/kg bodyweight.

METHODS: Five healthy Saanen goats, aged 12–14 months and weighing 35–40?kg, were used for a three phase cross-over design with a 10-day washout period, with meloxicam administered I/V, then orally and S/C. Heparinised blood samples (5?mL) were collected from all animals prior to drug administration (0 hours) and subsequently up to 96 hours. Concentrations of meloxicam in plasma were measured using high performance liquid chromatography. Concentration-time curves were fitted and pharmacokinetic parameters were estimated for each administration group.

RESULTS: Subcutaneous administration of meloxicam exhibited unique plasma distribution characteristics that differed from oral and I/V administration. Mean peak plasma concentrations were greater (1.91 (SD 0.39) vs. 0.71 (SD 0.17) µg/mL) and the time to reach them shorter (3.20 (SD 1.64) vs. 14.33 (SD 2.19) hours) following S/C compared with oral administration (p<0.05). The terminal half-life was longer (15.16 (SD 4.74) vs. 10.69 (SD 1.49) hours) and the MRT was shorter (15.67 (SD 2.37) vs. 24.33 (SD 3.12) hours) following S/C than oral administration (p<0.05), but bioavailability was similar (98.24 (SD 9.62) vs. 96.49 (SD 10.71)%).

CONCLUSION AND CLINICAL RELEVANCE: Subcutaneous administration of meloxicam resulted in long-term presence of drug at high concentration in goat plasma. This unique plasma disposition characteristic may offer an advantage in some clinical cases towards potentially improving the treatment efficacy in goats.     

猪生长激素(PST)脂质体代谢动力学的研究

在猪体内注射脂质体 ,研究其在体内的药物动力学 ,分析其血浆中生长激素浓度随时间的变化曲线 ,确定其释药模型为单室模型 ,求出各项动力学参数 ,结果为PST脂质体的缓释效果显著 ,缓释时间长达7天以上     

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.