盐酸千金藤碱在Beagle犬体内的药动学

目的 探讨盐酸千金藤碱在Beagle犬体内药代动力学特征。方法 采用液-质联用法测定Beagle犬静脉滴注盐酸千金藤碱1.0,3.0和10.0 mg·kg^-1后的血药浓度,使用3P97软件计算药动学参数。结果 静脉滴注盐酸千金藤碱注射液1.0,3.0和10.0 mg·kg^-1后, 血浆平均滞留时间(MRT)依次为8.6±7.0, 14.5±2.5和(18.3±5.8)h;血浆半衰期(T_1/2)分别为8.59±7.02, 14.55±2.46和(18.27±5.77)h;平均血药峰浓度(c_max)分别为(125.6±65.4), (262.6±95.1)和(1672.0±400.5)μg·L^-1;平均药时曲线下面积(AUC_0-tn)值分别为389±213, 1377±428和(13666±4330)μg·h·L^-1;平均清除率(Cl)分别为4.57±6.20, 2.14±0.66和(0.77±0.28)L·h^-1;平均表观分布容积(V_d)分别为27.2±11.4, 44.8±15.8和(19.9±9.7)L·kg^-1。结论 千金藤碱在Beagle犬体内代谢过程基本符合三室模型,主要药代动力学参数表现出一定的剂量相关性。     

盐酸小檗碱对大鼠体内他克莫司药动学的影响

目的:研究盐酸小檗碱单次、多次给药对大鼠体内他克莫司药动学的影响,为两者联合用药提供参考。方法:将30只大鼠随机分为5组,每组6只,第1组大鼠单次灌胃他克莫司;第2组大鼠每日灌胃他克莫司2次,连续给药1周;第3组大鼠先单次灌胃盐酸小檗碱,5 min后单次灌胃他克莫司;第4组大鼠先每日灌胃他克莫司2次,连续给药1周,第8天时先灌胃盐酸小檗碱5 min后再灌胃他克莫司1次;第5组大鼠每日灌胃盐酸小檗碱2次,每次间隔5 min后相应灌胃他克莫司1次,连续给药8 d。盐酸小檗碱给药剂量均为200 mg/kg,他克莫司给药剂量均为0.945 mg/kg。末次灌胃他克莫司后0、5、15、30 min和1、2、3、4、6、8、12 h,分别从各组大鼠的眼眶后静脉丛取血约0.3 m L,采用液相色谱-串联质谱法(LC-MS/MS)测定大鼠全血中他克莫司的浓度,应用DAS2.0软件进行药动学研究。结果:与第1组比较,第3组大鼠体内的他克莫司药动学参数AUC_(0-12) h、AUC0-∞和MRT0-12 h显著降低(P<0.05),第4组大鼠体内他克莫司所有药动学参数差异均无统计学意义(P>0.05);与第2组比较,第4组大鼠体内他克莫司药动学参数AUC_(0-12) h显著降低、CLz显著升高(P<0.05),第5组大鼠体内他克莫司所有药动学参数差异均无统计学意义(P>0.05)。结论:单次、多次灌胃盐酸小檗碱均对大鼠体内他克莫司的药动学有影响,表现在血药浓度有下降的趋势,需谨慎联用。     

重组水蛭素肠溶胶囊单次和多次给药在Beagle犬体内的药动学研究

目的:研究重组水蛭素肠溶胶囊单次和多次给药在Beagle犬体内的药动学特征。方法:取12只Beagle犬按随机对照法分为单次ig组和单次iv组,每组6只,按0.2 mg/kg ig或iv重组水蛭素,收集血样;清洗2周后12只犬按0.2 mg/kg ig重组水蛭素,连续给药7 d,收集血样,作为多次ig组。采用酶联免疫吸附法测定血浆中重组水蛭素浓度,以DAS 2.0软件计算药动学参数。结果:单次ig和单次iv重组水蛭素在Beagle犬体内药动学特征均符合二室模型,ig重组水蛭素肠溶胶囊的绝对生物利用度为(14.908±1.868)%;单次ig组和多次ig组犬体内重组水蛭素的t_(peak)分别为(2.105±0.243)、(3.000±0.000)h,t_(1/2β)分别为(8.660±2.965)、(14.870±2.710)h,c_(max)分别为(10.700±0.872)、(12.05±1.587)ng/m L,AUC_(0-1 440 min)分别为(55.250±4.386)、(58.978±6.002)ng·h/m L,两组间差异无统计学意义(P>0.05)。结论:ig重组水蛭素肠溶胶囊可一定程度被吸收入血;连续多天ig重组水蛭素肠溶胶囊在犬体内不产生蓄积,不改变其药动学特征。     

9-O-小檗碱葡萄糖苷在大鼠体内的药动学研究

目的:研究9-O-小檗碱葡萄糖苷(BOG)在大鼠体内的药动学参数。方法:采用高效液相色谱法测定大鼠血浆中小檗碱(BBR)、小檗红碱(BRB)、9-O-辛基小檗碱(BOO)、BOG的血药浓度,色谱柱为PREP-ODSC18(250mm×4.6mm,5μm),流动相为乙腈-醋酸缓冲液(醋酸铵7.7g,冰醋酸12mL,以蒸馏水定容至500mL)=40∶60(V/V),流速为1mL·min-1,柱温为室温,检测波长为345nm,进样量为20μL。用PKSolver软件计算药动学参数。结果:各组分分离效果良好,无杂质峰干扰。BBR检测浓度在1.0～75.0μg·L-1范围内与峰面积积分值呈良好线性关系。BOG的口服生物利用度与BBR、BRB、BOO比较有显著提高,BOG的Cmax与AUC0～t分别为BBR的9.3和11.1倍,达到63.438μg·L-1、267.994μg·h·L-1。结论:亲水性糖苷化修饰有助于提高BBR生物利用度。     

小檗碱对葛根素在大鼠体内药动学的影响

目的观察小檗碱对葛根素在大鼠体内药动学的影响。方法建立高效液相色谱（HPLC）法测定大鼠血浆中葛根素的浓度。大鼠灌胃给予葛根素（100 mg·kg^-1）及葛根素和小檗碱混合物（100 mg·kg^-1＋50 mg·kg^-1、100 mg·kg^-1＋100 mg·kg^-1、100 mg·kg^-1＋200 mg·kg^-1）,用HPLC法测定大鼠给药后不同时间血浆葛根素的浓度,DAS ver1.0数据处理软件计算药动学参数。结果葛根素在0.10-10.00 mg·L^-1范围内线性良好（r=0.999 5）。合用小檗碱前后葛根素的主要药动学参数Cmax分别为（0.54±0.05）、（0.59±0.03）、（0.67±0.02）、（0.73±0.03）mg·L^-1;AUC0-∞分别为（4.90±2.91）、（4.63±2.11）、（3.42±2.44）、（6.18±2.57）mg·L^-1·h^-1;CL分别为（26.92±16.24）、（25.94±13.36）、（44.58±30.36）、（18.82±8.47）L·h-1·kg^-1。结论高剂量小檗碱可提高葛根素在大鼠体内的吸收。     

青藤碱肠溶片在Beagle犬体内药动学研究

目的:研究口服青藤碱肠溶片在Beagle犬体内的药动学。方法:8只Beagle犬口服青藤碱肠溶片(10mg·kg-1)0、15、30、60、90、120、240、480min后分别从前肢静脉取血2mL,采用高效液相色谱法测定并计算血药浓度,用3p97软件计算药动学参数。结果:青藤碱肠溶片在犬体内药-时曲线符合一室模型,主要药动学参数tmax为(69.66±16.41)min,Cmax为(0.13±0.02)μg·mL-1,t1/2ke为(87.62±28.26)min,AUC0～T为(28.43±3.48)μg·min·mL-1。结论:Beagle犬口服青藤碱肠溶片后在体内吸收迅速,消除较快。     

黄连、木香药对提取物中盐酸小檗碱在大鼠血浆中的药动学研究

目的大鼠灌胃黄连-木香药对提取物后,测定盐酸小檗碱在大鼠血浆中的药动学参数,研究药对配伍后对盐酸小檗碱在大鼠血浆中的影响。方法采用高效液相色谱法测定大鼠灌胃后血浆中盐酸小檗碱的含量,色谱柱：Diamonsil C18（150mm×4.6mm,5μm）;流动相：乙腈-水（42∶58）,每100mL含有0.34g磷酸二氢钾,0.17g十二烷基硫酸钠;流速：1.0mL·min^-1;检测波长：349nm,柱温：35℃。结果药对提取物药动学参数：MRT（0-24）（12.470±1.538）h,MRT（0→∞）（29.711±7.176）h,AUC（0→24）（17.797±7.956）mg·L-1·h^-1,AUC（0→∞）（92.522±53.784）mg·L-1·h^-1,Tmax2h,Cmax（1.360±0.042）mg·L^-1。结论黄连、木香药对配伍后,采用DAS2.0软件处理,房室模型拟合分析,药室模型符合一房室模型。     

吉非替尼乳剂单次与多次给药后在大鼠体内的药动学研究

目的:研究吉非替尼乳剂单次和多次给药后在大鼠体内的药动学特征。方法:将大鼠分为单次给药组和多次给药组。单次给药组大鼠分为吉非替尼原料药组(50 mg/kg)和吉非替尼乳剂组(50 mg/kg),每组6只,灌胃给药1次。多次给药组大鼠分为吉非替尼原料药组(50 mg/kg)和吉非替尼乳剂组(50 mg/kg),每组8只,连续灌胃给药7 d,每天1次。吉非替尼原料药组大鼠于给药前和给药后1、2、2.5、3、3.5、3.75、4、4.25、4.5、6、8、12和24 h取血0.3 mL,吉非替尼乳剂组大鼠于给药前和给药后(多次给药组为给药7 d后)2、4、6、8、9、10、11、12、13、14、16、24、36和48 h取血0.3 mL,采用高效液相色谱法测定大鼠血浆中吉非替尼的血药浓度,绘制药-时曲线,并用DAS 2.0软件拟合药动学参数。结果:单次给药后,与吉非替尼原料药组tmax[(2.67±0.75)h]、MRT0-24 h[(8.68±0.91)h]、MRT0-∞[(14.20±3.45)h]比较,吉非替尼乳剂组tmax[(8.33±4.41)h]、MRT0-48 h[(15.00±1.60)h]、MRT0-∞[(17.60±2.66)h]均显著增加(P<0.05)。多次给药后,与吉非替尼原料药组tmax[(6.79±3.75)h]、AUC0-48 h[(41.10±8.92)mg·h/L]、Vz/F[(16.30±5.45)L/kg]、CLz/F[(0.94±0.19)L/(h·kg)]、MRT0-48 h[(10.10±0.36)h]比较,吉非替尼乳剂组Vz/F[(44.20±30.30)L/kg]、CLz/F[(1.89±1.56)L/(h·kg)]、MRT0-48 h[(16.20±2.52)h]均显著增加(P<0.05),AUC0-48 h[(38.70±26.20)mg·h/L]显著减少(P<0.05),tmax[(10.40±3.25)h]增加,但差异无统计学意义。结论:与吉非替尼原料药比较,单次和多次给药吉非替尼乳剂,均可延长药物的达峰时间;本研究结果可为吉非替尼新型给药系统的研究提供参考。     

合用盐酸小檗碱对环孢素A人体药动学的影响

目的:研究合用盐酸小檗碱(Ber)对肾移植受者和健康受试者环孢素A(CsA)药动学的影响,以分析两药相互作用发生的部位.方法:采用自身对照的方法,12例健康受试者和6例肾移植术后1个月的患者在个体CsA剂量不变的前提下,改变给药途径、两药同时或分开服用和改变合用频率等条件,按时间点采集血样,用FPIA法测定全血CsA浓度,并计算出药动学参数.结果:肾移植受者合用Ber和CsA后,CsA的AUC平均增加(34.5±17.8)%;口服6mg·kg-1CsA和Ber 0.3g,bid,末次两药分开服用的健康受试者平均AUC没有增加;口服3mg·kg-1CsA和Ber 0.3g,bid,末次两药同时服用的健康受试者平均AUC增加(19.2±10.4)%;静注3mg·kg-1CsA和口服Ber 0.3g,bid的健康受试者平均AUC减少(16.0±7.2)%.结论:两药必须同时服用方可发生相互作用,只有两药均在肠道时,CsA的吸收才会增加,提示肠道可能是Ber影响CsA吸收的作用部位之一,Ber可能增加CsA的吸收或减少肠代谢.Ber与CsA同时口服可增加CsA的生物利用度.     

黄连、木香药对提取物中盐酸小檗碱在大鼠血浆中的药动学研究

目的 大鼠灌胃黄连-木香药对提取物后,测定盐酸小檗碱在大鼠血浆中的药动学参数,研究药对配伍后对盐酸小檗碱在大鼠血浆中的影响。方法 采用高效液相色谱法测定大鼠灌胃后血浆中盐酸小檗碱的含量,色谱柱：Diamonsil C18(150 mm×4.6 mm,5 μm);流动相：乙腈-水(42∶58),每100 mL含有0.34 g磷酸二氢钾,0.17 g十二烷基硫酸钠;流速：1.0 mL·min-1;检测波长：349 nm,柱温：35 ℃。结果 药对提取物药动学参数：MRT(0-24)(12.470±1.538)h,MRT(0→∞)(29.711±7.176)h,AUC(0→24) (17.797±7.956)mg·L-1·h-1,AUC(0→∞)(92.522±53.784)mg·L-1·h-1,Tmax 2 h,Cmax(1.360±0.042)mg·L-1。结论 黄连、木香药对配伍后,采用DAS2.0软件处理,房室模型拟合分析,药室模型符合一房室模型。     

6β-纳曲醇单次和连续肌内注射给药在犬体内的药代动力学

研究6β-纳曲醇单次和连续肌内注射给药在犬体内的药代动力学。Beagle犬 (n = 4) 肌内注射6β-纳  曲醇0.2 mg·kg⁻¹, 每日1次, 连续7日。用反相高效液相-电化学检测法测定血浆6β-纳曲醇浓度。Beagle犬单次 (第一次) 及连续给药 (最后一次) 后的血药浓度经时变化过程均符合血管外给药一级吸收二室模型 (R² > 0.999), 药代动力学参数分别为t_1/2α (0.26 ± 0.23) 和 (0.19 ± 0.18) h, t_1/2β (4.77 ± 1.65) 和 (5.79 ± 1.50) h, C_max (81.65 ± 5.61) 和 (79.82 ± 10.5) ng·mL⁻¹, t_peak (0.27 ± 0.07) 和 (0.18 ± 0.08) h, CL_s (1.20 ± 0.06) 和 (1.12 ± 0.07) L·kg⁻¹·h⁻¹, V/F_c (1.94 ± 0.15) 和 (2.10 ± 0.27) L·kg⁻¹, AUC_0−t (166.82 ± 7.68) 和 (173.23 ± 9.49) ng·h·mL⁻¹。第一次和最后一次给药的药代动力学参数无显著性差异 (P > 0.05)。连续给药期间, 血药峰浓度和谷浓度的平均值分别为  (79.03 ± 10.3) 和 (1.50 ± 0.93) ng·mL⁻¹。结果显示, 6β-纳曲醇在犬体内的药物代谢过程符合一级吸收二室模型, 得到了相应的药代动力学参数; 连续给药对原形药物代谢过程基本无影响。     

西罗莫司固体分散体在Beagle犬体内的药动学研究

目的研究自制西罗莫司固体分散片在Beagle犬体内的药动学。方法6只Beagle犬分别按单剂量给药方案和多剂量给药方案口服西罗莫司受试制剂和参比制剂;采用UPLC-MS/MS法测定Beagle犬给药后不同时间的全血血样浓度。结果西罗莫司线性范围为0.50~20.00ng·mL^-1。Beagle犬单次口服西罗莫司受试制剂和参比制剂后的C max市售片>C max自制片,T max市售片C SSmax自制片,T max市售片相似文献   

Pharmacokinetics of dihydrocodeine and its active metabolite after single and multiple oral dosing

AIMS: The pharmacokinetics of dihydrocodeine (DHC) and its active metabolite dihydromorphine (DHM) were assessed after a single oral dose of DHC and after increasing doses of DHC at steady-state. Methods Twelve healthy male volunteers (18-45 years, CYP2D6 extensive metabolizers (EMs), MR<1 took a single oral dose (s.d.) of DHC 60 mg after breakfast. After 60 h DHC 60 mg was administered twice daily for 3 days, the dose was increased to 90 mg twice daily for 3 days, the final dose of 120 mg was administered twice daily for 3 days (multiple dose: m.d.). Blood sampling and urine collection: during 60 h after s.d. and during 12 h after m.d. Results No significant differences in the area under the curve (AUC) of both, DHC and DHM could be detected after a single oral dose of 60 mg DHC (AUC (0,infinity)) and during steady-state doses of 60 mg DHC (AUC(0,12 h)). During increasing steady-state doses of DHC, the data showed a dose linearity of AUC, maximal serum concentration (Cmax ) and minimal steady-state serum levels (Cssmin) of both, DHC and DHM (P<0.0001), point estimates of DHC dose corrected AUCs were well within the bioequivalence range (60 mg: 0.989; 90%CI 0.951-1. 028, 90 mg: 0.997; 90%CI 0.959-1.036, 120 mg: 0.977; 90%CI 0.940-1. 016). O-demethylation from DHC to DHM remained constant within the increasing steady-state doses of DHC in the 12 extensive metabolizers of CYP2D6. CONCLUSIONS: In the studied dose range (60-120 mg) the pharmacokinetics of DHC and its active metabolite DHM are linear in EMs of CYP2D6.     

家犬单剂量和多剂量口服阿昔莫司缓释制剂的药代动力学和生物等效性研究

目的研究阿昔莫司缓释片在家犬体内单剂量和多剂量的药代动力学和生物等效性。方法测定6只家犬单剂量和多剂量口服缓释片和普通胶囊后的血药浓度。结果阿昔莫司的药-时曲线符合非隔室模型。单剂量给药后，缓释片和普通胶囊的AUC分别为(158±30)和(147±37) μg·h·mL^-1；T_max分别为(4.3±0.8)和(2.6±1.3) h；C_max分别为(29±6)和(42±10) μg·mL^-1；T_1/2分别为(2.3±0.7)和(1.60±0.10) h；MRT分别为(6.0±0.8)和(3.9±0.7) h；F_r为(108±16)%。多剂量给药后，缓释片和普通胶囊的AUC分别为(209±23)和(195±26) μg·h·mL^-1；T_max分别为(6.3±0.8)和(3.4±1.5) h；C_max分别为(27±4)和(36±5) μg·mL^-1；Cmin分别为(2.2±1.0)和(0.20±0.20) μg·mL^-1；C_av分别为(8.7±1.0)和(8.1±1.1) μg·mL^-1；FI分别为(293±73)%和(448±91)%；F_r为(114±19)%。结论单剂量实验的双单侧检验结果表明：缓释片和普通胶囊生物等效；缓释片具有良好的缓释效果。多剂量实验结果表明：缓释片和普通胶囊生物等效；缓释片的波动系数优于普通胶囊。     

Pharmacokinetics of single oral and multiple intravenous and oral administration of acebutolol enantiomers in a rat model

Acebutolol (AC), is a chiral, β -adrenergic blocking agent which possesses partial agonist activity and is metabolized to an equipotent chiral metabolite, diacetolol (DC). The enantiomeric disposition of AC is reported following racemic administration as a single oral (p.o., 50 mg kg⁻¹) or as a multiple thrice daily intravenous (i.v.) or p.o. dosing for four days in male Sprague–Dawley rats (n =6). Enantiomeric concentrations of AC and DC in plasma and urine were determined using a stereospecific HPLC assay. The bioavailabilities of R- and S-enantiomer were 0.40 and 0.39 after single dose administration of AC respectively. These values were increased to 0.51 and 0.53 after multiple dosing. Although no significant differences were found in AUC_0–∞ after single i.v. as compared with AUC_0–τ after multiple i.v. dosing of AC, the 39 and 45% increase in mean AUC_0–τ were found after multiple p.o. dosing over the corresponding AUC_0–∞, for the single p.o. dose of AC for R- and S-enantiomer, respectively. The disposition of DC as well as the urinary excretion of metabolite was stereoselective in favor of R-enantiomer after oral administration of AC. These results indicate that AC enantiomers have low availability and moderate extraction through the first-pass metabolism in a rat model. The higher AUC values after p.o. multiple dosing may suggest a saturable first-pass metabolism of AC. © 1998 John Wiley & Sons, Ltd.     

Pharmacokinetics of canrenone and metabolites after base hydrolysis following single and multiple dose oral administration of spironolactone

Summary The pharmacokinetics of canrenone and total metabolites after base hydrolysis was studied in eight young volunteers following single and multiple dose oral administration of spironolactone. The plasma levels of canrenone and total metabolites were fitted to a two-compartment open model with a first-order absorption process. From our eight normal subjects studied, the harmonic mean of the distributive half-life (t_1/2) of canrenone was found to be 1.66 h, and the harmonic mean of the terminal elimination half-life (t_1/2) to be 22.6 h. Harmonic means of the distributive and elimination half-lives of total metabolites after base hydrolysis were 2.48 h and 28.8 h respectively. The accumulation ratio of canrenone was 2.53, whereas that of total metabolites was 1.89. Despite the fact that spironolactone has been shown to induce hepatic metabolism of other drugs, no evidence of autoinduction was noted in the present study, as plasma levels of canrenone and total metabolites were found to obey a linear two-compartment model with reproducible absorption and disposition after single and multiple doses.     

多剂量甲磺酸帕珠沙星氯化钠注射液在健康人体的药代动力学

目的研究甲磺酸帕珠沙星氯化钠注射液（氟喹诺酮类抗生素）在健康人体内连续给药的药代动力学特征。方法12名受试者同时予以静滴甲磺酸帕珠沙星氯化钠注射液500mg，间隔12h，每日2次，连续7天，用高效液相色谱法测定给药后不同时间的血、尿浓度，求得主要药代动力学参数。结果其血药浓度约在第4天达稳态，Cmax为（13．46±1．87）mg·L^-1，Cav为（2．72±0．36）mg·L^-1，AUC。为（32．70±4．28）mg·L^-1·h，DF为490．43％，FI为98．15％，尿中的药物累积排泄率〉90％，与单次给药无明显差异。结论每日2次，静滴帕珠沙星500mg，连续7天，药物在体内无蓄积，受试者耐受性良好。     

Pharmacokinetics of sulphinpyrazone and its major metabolites after a single dose and during chronic treatment

Summary The pharmacokinetics of bupropion and 3 of its basic metabolites were determined in 8 young, healthy, male volunteers after single and multiple oral doses of bupropion. Plasma profiles were obtained: 1) after a single 100 mg oral dose of bupropion hydrochloride, 2) following administration of 100 mg 8-hourly for 14 days and 3) again after a single 100 mg dose 14 days later. Plasma concentrations of the parent drug and metabolites were determined by high-performance liquid chromatography. Saliva secretion and pupil diameters were measured, subjective assessments of sleep made using visual analogue scales and side effects, blood counts and biochemistry were monitored. After the first dose mean elimination half lives (t_1/2) of bupropion, and metabolites I and II were 8, 19 and 19 h respectively. On repeated administration there was little accumulation of the parent drug and no evidence for induction of its own metabolism. Accumulation of I was consistent with its rate of elimination after single doses while that of II was greater than predicted with prolongation of t_1/2 to 35 h. Metabolite III was barely detectable after single doses but its accumulation on multiple dosing was consistent with its long half life (35 h) determined on occasion 2. Saliva secretion was significantly reduced during the multiple dosing period but there were no complaints of dry mouth. Subjective assessments of sleep were not significantly altered though one subject reported vivid dreams. There were no other adverse reactions.Abbreviations k_a first order rate constant for absorption or appearance - k_el first order rate constant for elimination - F extent of bioavailability - D administered dose (as free base) - k₁₂ first order distribution rate constant into peripheral compartment - k₂₁ first order distribution rate constant from peripheral compartment - k₁₀ first order elimination rate constant from central compartment - first order elimination rate constant of rapid disposition phase - first order elimination rate constant of slow disposition phase - V_z apparent volume of distribution - V_c apparent volume of distribution of central compartment - t time after drug administration - t_o lag time for absorption - Cp_(t) concentration in plasma at time t - n number of doses - Cp_(tn) concentration in plasma at time t after n^th dose - dose interval - CL clearance uncorrected for bioavailability F     

盐酸双苯氟嗪在Beagle犬体内的药代动力学

目的研究新型钙通道阻断剂盐酸双苯氟嗪在Beagle犬的药代动力学。方法Beagle犬18只,随机分为低、中、高3个剂量组,分别单次股静脉注射1.5、3.0和6.0 mg.kg-1的盐酸双苯氟嗪溶液,后肢股静脉分时取血,处理,反相高效液相法(RP-HPLC)测定血浆中盐酸双苯氟嗪的浓度,应用3P97软件计算主要药代动力学参数。结果所建立测定方法的特异性、最低检测限、最低定量限、提取回收率、日内和日间精密度及稳定性均符合药代动力学分析方法的要求。单次静脉注射后,盐酸双苯氟嗪在Beagle犬体内的药代动力学过程符合开放二房室模型,低、中、高3个剂量的主要药代动力学参数:T12β分别为24.7、24.2和29.6 h;AUC分别为0.44、1.12和2.86 g.min.L-1;Vc分别为1.30、1.22和1.28 L.kg-1;CL分别为3.4×10-3、2.7×10-3和2.1×10-3L.kg-1.min-1。结论本研究建立的RP-HPLC法能够满足盐酸双苯氟嗪药代动力学研究的要求,静脉注射盐酸双苯氟嗪在犬体内消除过程属于两相消除,AUC与剂量呈线性相关。     

单剂量口服匹伐他汀钙片在中国健康志愿者的药代动力学和安全性

目的 研究国产匹伐他汀钙片(降血脂药)在中国健康志愿者体内单次给药的药代动力学特征及安全性.方法 选择中国健康受试者12例,按3×3拉丁方设计,分别单次给予匹伐他汀钙片1,2,4 mg后,采用液相色谱-串联质谱联用法测定不同时间血中匹伐他汀的浓度,以DAS 2.0软件进行数据处理,求算药代动力学参数.结果 3个不同剂量组匹伐他汀的主要药代动力学参数:t_(1/2β)分别为(11.39±7.66),(10.00±7.30),(11.30±7.95)h;t_(max)分别为(0.83±0.29),(0.73±0.20),(0.85±0.46)h;C_(max)分别为(30.48±11.66),(60.80±22.97),(120.98±35.51)ng·mL~(-1);AUC_(0→72h)分别为(93.19±26.61),(179.46±52.86),(364.37±94.74)ng·mL~(-1)·h;AUC_(0→∞)分别为(96.70±27.42),(183.34±53.62),(372.86±95.84)ng·mL~(-1)·h;各剂量组的C_(max)、AuC_(0-72h)、AUC_(0→∞)随剂量的增加而成比例的增大,各组的K_(10)、t_(max)、t_(1/2β)、MRT_(0-72)、MRT_(0→∞)、CL/F、V/F等差异无统计意义.结论 口服给药剂量为1～4 mg时,匹伐他汀钙片在中国健康人体内具有线性药代动力学特征,其代谢特征基本与文献报道一致.