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.     

Sanguinarine metabolism and pharmacokinetics study in vitro and in vivo

Sanguinarine (SA) is a benzo[c] phenanthridine alkaloid which has a variety of pharmacological properties. However, very little was known about the pharmacokinetics of SA and its metabolite dihydrosanguinarine (DHSA) in pigs. The purpose of this work was to study the intestinal metabolism of SA in vitro and in vivo. Reductive metabolite DHSA was detected during incubation of SA with intestinal mucosa microsomes, cytosol, and gut flora. After oral (p.o.) administration of SA, the result showed SA might be reduced to DHSA in pig intestine. After i.m. administration, SA and DHSA rapidly increased to reach their peak concentrations (C_max, 30.16 ± 5.85, 5.61 ± 0.73 ng/ml, respectively) at 0.25 hr. Both compounds were completely eliminated from the plasma after 24 hr. After single oral administration, SA and DHSA rapidly increased to reach their C_max (3.41 ± 0.36, 2.41 ± 0.24 ng/ml, respectively) at 2.75 ± 0.27 hr. The half-life (T_1/2) values were 2.33 ± 0.11 hr and 2.20 ± 0.12 hr for SA and DHSA, respectively. After multiple oral administration, the average steady-state concentrations (C_ss) of SA and DHSA were 3.03 ± 0.39 and 1.42 ± 0.20 ng/ml. The accumulation indexes for SA and DHSA were 1.21 and 1.11. The work reported here provides important information on the metabolism sites and pharmacokinetic character of SA. It explains the reasons for low toxicity of SA, which is useful for the evaluation of its performance.     

HPLC-MS/MS法检测血根碱在鸡体内的药代动力学研究

为了建立给鸡灌胃血根碱后同时测定鸡血浆中血根碱及二氢血根碱浓度的HPLC-MS/MS检测方法,并评价血根碱在鸡体内的药代动力学特征,采用甲醇提取鸡血浆中的血根碱及代谢物二氢血根碱,以0.2%甲酸水(A)-乙腈(B)为流动相,选用Agilent Poroshell 120 EC C18(2.1 mm×150 mm,2.7μm)色谱柱进行色谱分离,采用电喷雾离子源(ESI)三重四极杆串联质谱进行分析,多重反应监测(MRM)方式进行检测。血根碱及代谢产物二氢血根碱均在0.1~50.0 ng/mL浓度范围内与色谱峰面积呈良好线性关系,提取回收率分别为88.95%~95.81%和82.00%~87.00%;日内及日间精密度(RSD)均小于15%;血根碱在鸡体内的药代动力学参数Cmax,Tmax,MRT,CL分别为0.90±1.053 ng/mL、0.38±0.30 h、5.11±0.74 h和44.09±3.05 h。血根碱在鸡体内血药达峰时间以及滞留在体内的平均时间较短,代谢物二氢血根碱的血药浓度是血根碱的血药浓度5.74倍,说明代谢物二氢血根碱的血药浓度远大于血根碱的血药浓度。该方法具有快速、灵敏度高、专属性强等特点,适用于同时测定鸡血浆中血根碱和二氢血根碱的血药浓度。     

HPLC测定大鼠肝微粒体温孵体系中二氢血根碱的含量

建立了测定大鼠肝微粒体温孵体系中血根碱代谢产物二氢血根碱含量的高效液相色谱法。色谱柱为Shimadzu VP-ODSShim-pack（150mm×4．6mm,5μm）;流动相为水：乙腈（37：63,V/V）;流速1mL／min;柱温35℃;检测波长285nm;进样量10μL。结果显示50nmol／L和1000nmol／L二氢血根碱标准溶液的方法回收率分别为101．72％和98．82％;50、100、500nmol／,L标准溶液的日内RSD分别为2．26％、2．57％和3．02％,日间RSD分别为6．21％、4．33％和3．95％：二氢血根碱在25-1000nmol／L内与峰面积呈良好的线性关系（r=0．9996）。本分析方法快速简便,灵敏度高,重现性好,符合方法学验证的要求,可满足二氢血根碱在体外代谢中的定量研究。