噁喹酸和氟甲喹在鳗鱼体内的药代动力学研究

研究了单次血管注射喹酸(Oxolinicacid)和氟甲喹(Flumequine)后,在鳗鱼(Muraenesoxcinereus)体内的代谢规律及残留情况。采用高效液相色谱-质谱联用(HPLC-MS)法进行喹酸和氟甲喹的检测,检测低限(LOD)1ng/ml;定量限(LOQ)5ng/ml。喹酸和氟甲喹的代谢过程均可以用一级代谢二室模型来描述,喹酸的分布半衰期:0·18h,消除半衰期:14·84h,总体清除率0·07L/kg·h;氟甲喹的分布半衰期:0·19h,消除半衰期:9·38h,总体清除率0·07L/kg·h。两种药物在鳗鱼体内都有很强的“首过效应”,易在胆汁中积累;给药72h后,喹酸和氟甲喹在可食用组织肌肉中的残留量分别为36·1ng/g和21·8ng/g,低于目前国外要求的最高残留量50ng/g和75ng/g。     

兽药替米考星及其临床应用

替米考星是一种动物专用的新型大环内酯类抗生素,临床主要应用于牛、猪、鸡、绵羊、山羊、兔等动物感染性疾病,特别是畜禽呼吸道疾病并取得显著疗效。该药具有抗菌活性强、药代动力学特征优良、用量少、毒性小等特点。临床应用表明:替米考星是一种安全有效的新型兽药,具有广阔的应用前景。     

土霉素在黑鲷体内的药物代谢动力学研究

首次报道了黑鲷口服土霉素的药物代谢动力学特征，用高效液相色谱法测定组织中的药物含量，药物在肌肉，血液，肝脏中的平均回归率分别为８５.61%,85.38%,82.005,该方法的检测限可达0.01μg/g，黑鲷１次口服剂量为７５mg/kg的土壤素后，其血液药物浓度－时间数据符合一室开放动力学模型，吸收速率常数（ka)为０.296/h，达峰时间（Ｔamx)为１０.635h,峰浓度（Ｃmax)为１.398μg/ml, 分布半衰期（Ｔ１／２a）为２.339h ,消除半衰期(T1/20β）为46.663h，药时曲线下面积（ＡＵＣ）为１１0.25mg/L.h，黑绸口服药物０.5h后在血液，肥肉，肝脏，肾脏４种组织中就可以检测到药物的存在，药物在１６h的采样点浓度达最高，分别为1.68μg/ml,1.68,2.52,6.77μg/g。     

克伦特罗在猪体内的生物利用度及药物动力学研究

６头体重４７．００±４．５７ｋｇ（Ｘ±Ｓ）的健康长白和大白杂交猪，拉丁方设计试验，按４ｍｇ／ｋｇ静注、肌注和内服克伦特罗，高效液相色谱法检测血浆中药物浓度，ＭＣＰＫＰ药代动力学程序处理药时数据。静注给药的药代动力学参数是：ｔ１／２α０．６２±０．１２ｈ，ｔ１／２β４．８７±１．５６ｈ，Ｖｄ（ａｒｅａ）４．４８±０．５６ｌ／ｋｇ，ＣｌＢ０．６３±０．１１ｌ／ｋｇ／ｈ，ＡＵＣ６．３９±１．２７μｇ／ｍｌ．ｈ。肌注给药的药动学参数是：ｔ１／２Ｋａ０．２２±０．１０ｈ，ｔ１／２α０．５６±０．２１ｈ，ｔ１／２β４．２５±１．１０ｈ，ｔｍａｘ０．６０±０．１３ｈ，Ｃｍａｘ１．２７±０．３５μｇ／ｍｌ，ＡＵＣ５．４８±１．２９μｇ／ｍｌ．ｈ，Ｆ８５．４０±４．６９％。内服给药的药动学参数是：ｔ１／２Ｋａ０．２８±０．１５ｈ，ｔ１／２Ｋｅ３．１５±０．３６ｈ，ｔｍａｘ１．４６±０．１９ｈ，Ｃｍａｘ０．６５±０．１３μｇ／ｍｌ，ＡＵＣ３．９３±０．９９ｍｇ／ｌ．ｈ，Ｆ６１．０２±１０．９０％。肌注给药的生物利用度与内服比较，差异极显著（Ｐ＜０．０１）。     

Toxicokinetics of the active doxorubicin metabolite, doxorubicinol, in sulphur-crested cockatoos (Cacatua galerita)

The pharmacokinetics of doxorubicinol, a cytotoxic metabolite of the anticancer drug, doxorubicin, were studied in four healthy sulphur-crested cockatoos (Cacatua galerita) after a 20 min intravenous infusion of 2 mg/kg. Plasma doxorubicinol concentrations were measured by HPLC. The pharmacokinetic parameters were estimated using a non-compartmental method. The mean (+/- SD) peak concentration was 8341 +/- 3132 microg/L at 17.5 +/- 5.0 min after the start of the infusion, and doxorubicinol concentrations declined biexponentially to 154.3 +/- 34.5 microg/L, 40 min after the end of the infusion. Systemic clearance was 0.940 +/- 0.473 L/h/kg, mean residence time was 0.165 +/- 0.133 h, and steady-state volume of distribution was 0.123 +/- 0.0526 L/kg. The terminal half-life was 0.660 +/- 0.611 h. Detectible but unquantifiable concentrations of doxorubicinol were present in the plasma ultrafiltrate of two birds during the infusion, indicating very extensive plasma protein binding. Physiological, haematological and biochemical monitoring over 3 weeks showed that doxorubicinol at a single infused dose of 2 mg/kg caused no toxicities of major concern.     

An in vivo analysis of the therapeutic and synergistic properties of Chinese medicinal formula Yin-Chen-Hao-Tang based on its active constituents

6,7-Dimethylesculetin (D), geniposide (G) and rhein (R) are the three major active ingredients of Yin-Chen-Hao-Tang (YCHT), a famous Chinese herbal formula, which has been shown to be clinically effective for treating hepatic injury (HI) syndrome. The present study was conducted to investigate the therapeutic and synergistic effects of COC (combination of D, G and R) on HI rats by combining pharmacokinetic with biochemical analysis strategy. Plasma was analyzed by using reversed-phase high performance liquid chromatography (RP-HPLC). Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) models were built to evaluate the therapeutic and synergistic effects of COC at the biochemical level. Here, we report that the COC combination could increase the plasma level, slow elimination rate, exert a more robust therapeutic effect than any one or two of the three individual compounds by hitting multiple targets in a rat model of HI. Overall, this beneficially accounts for the popular view that traditional Chinese medicine (TCM) formula usually takes multi-component to exert their therapeutic effects. We suggest that dissecting the mode of action of clinically effective formula to be capable of producing a sufficient effect at low doses.     

Permeability determination and pharmacokinetic study of nobiletin in rat plasma and brain by validated high-performance liquid chromatography method

In the present study, we are reporting permeability and pharmacokinetics of nobiletin in rat plasma and brain, using a validated reverse phase high performance liquid chromatographic method. Protein precipitation method was used for the extraction of nobiletin and coumarin (IS) from rat plasma and brain tissue. The system was run in isocratic mode with mobile phase consisting of potassium dihydrogen ortho-phosphate (pH 4.5; 0.04 mM) and acetonitrile in ratio of 50:50, v/v. The total chromatographic run time was 9.0 min. The method was proved to be accurate and precise at linearity range of 0.05–10 μg/mL with a correlation coefficient (r) of ≥ 0.994 in rat plasma and ≥ 0.995 in rat brain. The intra- and inter-day precision and accuracy values are found to be within the assay variability limits as per the FDA guidelines. Nobiletin was found stable in the battery of stability studies viz., bench-top, auto-sampler, freeze/thaw cycles and long term storage in a freezer at − 70 ± 10 °C. Maximum concentrations of nobiletin in both plasma and brain were observed at 1 h after single oral dosing (50 mg/kg). The maximum concentration in plasma and brain were 1.78 and 4.20 μg/mL, respectively. The AUC_0–t in plasma and brain were 7.49 and 20.66 μg·h/mL, respectively. The mean elimination half life (t_1/2) in plasma and brain were 1.80 and 11.42 h, respectively. The Parallel Artificial Membrane Permeability Assay (PAMPA) permeability of nobiletin was found to be high at both pH 4.0 and 7.0.     

SMM在实验性肾功能损害家兔体内的药物动力学研究

分析了SMM在健康家兔及肾损害兔体内的药物动力学过程。12只家兔分为A、B两组。A组为健康对照组,B组为肾功能损害病理模型组。A、B两组家兔均以140 mg/kg(SMM)剂量耳静脉注射SMM-Na,给药前心脏采血0.5 mL,作为空白对照。分别于给药后0.08、0.25、0.5、1、2、3、4、6 h各采血0.5 mL。以Annino法分析游离SMM血药浓度。结果显示,SMM在家兔体内药物动力学配置符合二室开放模型。药时曲线最佳方程为:C正常=13.910e-6.830t 32.569e-1.076t,C肾损害=15.748e-4.542t 27.473e-0.323t。肾损害时药动学参数与健康时的比较,α下降了33.49%;β下降了69.98%;t1/2α增加了41.03%;t1/2β增加了237.5%;AUC增加了33.49%;CLB下降了69.98%。表明家兔肾功能损害后,SMM在其体内消除显著变慢。提示在肾脏损害时应相应增大SMM给药间隔时间或减小给药剂量。     

阿莫西林注射用混悬液及其在猪体内的药物动力学研究

以阿莫西林为原料,注射用大豆油为溶媒,成功研究出阿莫西林注射用混悬液,并对制剂进行了稳定性研究。所有参试样品的相对含量、外观性状、粒度、分解产物等指标均无明显变化,表明该制剂对光、热稳定。选用5头健康猪进行了药物动力学研究,按15mg/kgB.W的阿莫西林剂量肌内注射,药时曲线符合一级吸收二室模型,主要动力学参数为:Tmax=0 53±0 17h,Cmax=12 33±0 47μg/ml,AUC=79 62±4 32(μg/ml)h,T1/2β=33 62±4 06h。结果表明,阿莫西林注射用混悬液在猪体内吸收缓慢,持效时间长。临床应用48h给药1次仍能维持对常见病原菌的有效血药浓度。     

硫酸多粘菌素E在猪体内的药代动力学和生物利用度研究

健康断奶仔猪 5头 ,分别进行单剂量肌注 (2 5和 5 0mg/kgb .w .)和静注 (2 5mg/kgb .w .)给药 ,并用微生物学方法对硫酸多粘菌素E在猪体内的药代动力学和绝对生物利用度进行了研究。以 3P97程序处理血药浓度—时间数据 ,结果表明 ,以 2 5和 5 0mg/kgb .w .的剂量肌注给药时 ,其血清中药物的峰浓度 (Cmax)分别为 3 73± 0 2 8μg/ml和 6 40± 0 1 8μg/ml,达峰时间分别为 32 2 2± 1 51min和 34 1 8± 1 76min ,消除半衰期 (t1 / 2 β)为 2 55 99± 1 3 65min和 2 64 0 8± 2 8 57min ;以 2 5mg/kgb .w .的剂量静注给药时 ,其消除半衰期 (t1 / 2 β)为 2 51 2 8± 1 2 53min。静注和肌注在体内的分布均为一级吸收二室模型。肌注 2 5和 5 0mg/kgb .w .剂量的注射液时 ,其平均绝对生物利用度分别为 98 30 %和 88 54 %。