氯沙坦对家兔环孢素A药代动力学影响的研究

目的研究氯沙坦对家兔环孢素A（CsA）药代动力学的影响。方法采用荧光偏振免疫法（FPIA法）测定6只家兔合用氯沙坦前后CsA的血药浓度,并对2组（单用CsA组和合用氯沙坦组）药代动力学参数进行分析。结果合用氯沙坦组的CsA峰浓度（Cmax）、曲线下面积（AUCν0-24）均显著升高（P〈0．01）,血浆清除率（cL）及表观分布容积（V）均显著降低（P〈0．05或P〈0．01）,其余药动学参数无显著性变化（P〉0．05）。结论合用氯沙坦可升高CsA的血药浓度,临床上其与CsA合用需监测CsA的血药浓度,保证治疗的安全有效。     

双环醇对利福平大鼠体内药动学的影响

目的:研究双环醇对利福平血药浓度及药动学的影响。方法:12只Wistar大鼠随机分为利福平(对照)组和双环醇+利福平(实验)组共2组,双环醇与利福平的剂量分别为15.85、63.4mg.kg-1,每天1次,连续给药4d。在第4天给药前和给药后0.25、0.5、1、1.5、2、4、6、8、12、24h取血,应用高效液相色谱法测定2组利福平的血药浓度,并计算药动学参数。结果:2组各时间点利福平血药浓度及药动学参数之间比较均无显著性差异(P>0.05)。结论:双环醇与利福平合用于大鼠体内后对利福平药动学无显著影响。     

氨溴索注射剂对多索茶碱在大鼠体内药动学的影响

目的研究氨溴索对多索茶碱（DP）在大鼠体内的药动学参数的影响。方法采用HPLE法测定16只大鼠单独给予DP和合并盐酸氨溴索给药后DP以及其代谢产物茶碱（TP）的血药浓度,用DAS药动学软件对DP血药浓度-时间数据采用非房室模型分析,求得DP在大鼠体内主要的药动学参数,并对其进行统计分析。结果2组大鼠DP药动学参数t1/2、AUC0→1、MRT0→7h、Vz/F、CL／F、tmax、ρmax差异均无统计学意义（P〉0．05）。但氨溴索与DP合并使用时,DP代谢产物TP的AUC0-7h2组差异具有统计学意义（P〈0．05）,合用组提高了38．77％。结论氨溴索对DP在大鼠体内动力学过程无影响,但有减缓DP的代谢产物TP代谢的趋势,两药同时使用时,应注意监测TP的血药浓度。     

盐酸尼卡地平凝胶家兔在体透皮吸收研究

进行了盐酸尼卡地平凝胶的家兔在体透皮吸收研究，评价月桂氮Chuo酮对其透皮吸收的促进作用。通过测定家兔皮肤给药后不同时间的血药浓度值，得到了血药－时间曲线，经拟合获得了透皮吸收的主要药动学参数，结果表明加入月桂氮Chuo酮后尼卡地平的峰浓（Cmax)，血药浓度曲线下面积（AUC0－24h)和平均滞留时间（MRT）三个参数均显著增加（P＜0．0001），而达峰时间（Tmax)和时滞（Tlag)两个参数无显著性改变（P＞0．05）。     

罗哌卡因在犬坐骨神经阻滞时的药代动力学

目的探讨罗哌卡因在犬坐骨神经阻滞时的药代动力学特点。方法选取健康杂种犬12只,按取血样本分为动脉组和静脉组,每组6只。动脉组取动脉血,静脉组取静脉血。2组肌内注射3％戊巴比妥钠30mg／kg麻醉后,分别采用0．5％罗哌卡因10mg／kg行单次坐骨神经阻滞,于罗哌卡因给药前,给药后10、20、30、40、60、90、120、150、180、240、360、720min分别抽取股动、静脉血5ml,采用反相高效液相色谱法测定血浆罗哌卡因浓度。计算药代动力学[分布半衰期（t1／2α）、消除半衰期（t1/2β）、达峰时间（Tmax）、峰值浓度（Cmax）、曲线下面积（AUC）、一阶矩曲线下面积（AUMC）、平均吸收时间（MAT）、平均残余时间（MRT）]参数。结果2组罗哌卡因阻滞犬坐骨神经时的血药浓度-时间曲线符合二室模型,t1/2α、t1/2β,Tmax,Cmax、AUC0-720min、AUC0-∞、AUMC0-72min、AUMC0-∞、MAT、MRT0-720min,MRT0-∞比较差异均无统计学意义（均P〉0．05）。结论动静脉血对罗哌卡因阻滞犬坐骨神经时的药代动力学无影响。     

健康人体内甲磺酸加替沙星对茶碱稳态药代动力学的影响

目的:研究甲磺酸加替沙星对健康人体内茶碱稳态药代动力学的影响。方法:采用HPLC法测定健康人体单独给药和合并甲磺酸加替沙星给药后茶碱的血药浓度,采用3P97药动学软件处理,选用非参数法计算药动学参数,Cmax和Tmax为实测值,AUC采用梯形法计算曲线下积分面积。主要药动学参数采用SPSS11.5软件进行统计分析。结果:单用和合用甲磺酸加替沙星后,茶碱的药动学参数Cmax、t1/2、CL、AUC0-12、AUC0-∞之间有显著性差异(P<0.01)。Cmax明显下降,t1/2明显减小,AUC0-12与AUC0-∞明显下降。结论:甲磺酸加替沙星对健康人体内茶碱稳态药动学有影响,两者合用可能降低茶碱疗效,提示两药合用应监测茶碱的血药浓度。     

双氯芬酸二乙胺凝胶贴剂的药动学

目的：研究自制的双氯芬酸二乙胺凝胶贴剂的兔体内的药动学特征。方法：外贴经皮给药，以德国上市贴剂Flector EP-flaster为参比制剂，用HPLC测定不同时间血药浓度，用3P97药动学程序进行处理，计算药动学参数，并对2种制剂在体内的主要药动学参数分别进行t检验。结果：兔透皮给予双氯芬酸二乙胺后的药动学过程符合一室模型，2种贴剂的药动学参数AUC、Cmax、tmax，t1/2（ka）、ka和Lag time差异无显著性（P〉0．05），而t1/2（ke）和ke差异有显著性（P〈0．05），CL／F和V／F差异有极显著性（P〈0．01）。结论：自制的双氯芬酸二乙胺凝胶贴剂与相应的德国贴剂相比．具有更缓释、长效的作用。     

酮康唑对家兔体内茶碱血药浓度及药动学参数的影响

目的：观察酮康唑对茶碱血药浓度及药动学参数的影响。方法：采用荧光偏振免疫分析法测定氨茶碱单用及与酮康唑合用后家兔体内茶碱血清浓度，并对两组药动学参数进行统计学处理。结果：酮康唑可使氨茶碱血药浓度明显降低；合并用药组Vd为4．70±1．48L，AUC为51．94±25．51mg/(L·h），对照组Vd为1．39±0．61L，AUC为75．74±11．29mg/(L·h），两组相比有显差异（P＜0．01和P＜0．05），其余药动学参数无显变化。结论：两药合用时应调整氨茶碱的给药量，并注意监测其血药浓度。     

2种硫辛酸制剂的人体药动学与生物等效性研究

目的：建立HPLC-MS法测定人血浆中硫辛酸的浓度,研究其在人体内的药代动力学和相对生物利用度,并进行生物等效性评价。方法：采用随机双周期两制剂交叉试验设计,22名男性健康志愿者分别单剂量口服硫辛酸胶囊（受试制剂）或硫辛酸片（参比制剂）200mg,用HPLC-MS法测定健康受试者的血药浓度,计算药代动力学参数,并对两种制剂做出等效性评价。ρmax、AUC0-t和AUC0-∞采用方差分析和双单侧t检验,tmax进行秩和检验。结果：受试制剂和参比制剂的药动学参数：tmax分别为（16±4）、（20±20）min,ρmax分别为（1490±359）、（1537±290）ng/mL,AUC0-t分别为（59559±18456）、（58210±15080）ng·mL-1.min,AUC0-∞分别为（60068±18556）、（58634±15126）ng·mL-1.min。以AUC0-t和AUC0-∞计算,硫辛酸胶囊的相对生物利用度为（102.97±18.28）%、（103.09±18.26）%。结论：经方差分析及双单侧t检验表明：ρmax、AUC0-t和AUC0-∞均接受受试制剂与参比制剂生物等效性的假设,tmax经秩和检验无统计学差异（P〈0.05）,可判断两种制剂是生物等效的。     

注射用头孢拉定对双黄连粉针药动学的影响

目的测定双黄连粉针中绿原酸在大鼠体内的药动学参数。方法利用建立的高效液相色谱法测定大鼠单独静脉注射双黄连粉针及与头孢拉定合用后绿原酸在大鼠体内的血药浓度,采用药动学程序Topfit2.0进行统计处理,计算非室模型药动学参数。结果单用双黄连粉针后绿原酸的药动学参数:t210.5h,ke1.37h-1,AUC0-t6.98μg.h.mL-1,MRT0.43h,Cltot111.0mL.min-1.kg-1,Vz5.01L.min-1.kj-1;合用头孢拉定后绿原酸的药动学参数:t210.53h,ke1.33h-1,AUC0-t8.07μg.h.mL-1,MRT0.45h,Cltot99.3mL.mL-1.kg-1,Vz4.50L.min-1.kg-1。结论头孢拉定不影响大鼠体内绿原酸的药动学过程。     

Pharmacokinetics of antituberculosis drugs in patients

The pharmacokinetics of rifampin, isoniazid, and ethambutol were determined in 26 ambulatory male patients (aged 49.5 +/- 9.9 yr) with tuberculosis. Rifampin and isoniazid were given individually or together, with or without ethambutol; studies were done after a single dose and after chronic administration. Under the study conditions, with large variability in the extent of disease and physical status and history of alcohol and tobacco abuse and narrow age range, the pharmacokinetics of these three antituberculosis drugs were not modified significantly by patient age. Furthermore, appreciable drug-drug interactions did not occur when the three drugs were administered concurrently. Self-induction of rifampin clearance by chronic dosing with the drug may lead to subtherapeutic levels of rifampin. Administration of isoniazid and ethambutol in two divided doses resulted in peak plasma concentrations below the accepted therapeutic levels of the two drugs. Our findings indicate that at least in the middle-aged patients with tuberculosis, the current single daily dose, multiple-drug regimen is therapeutically sound pharmacokinetically, and clinicians do not have to make adjustments in dosages of these drugs for age and the extent of disease.     

异烟肼对利福平的药动学影响

目的：研究异烟肼对利福平的体内药物动力学影响。方法：采用自身对照法2周期两制剂的交叉实验设计，比较了联合给药与单独给药的动力学参数。结果：异烟肼对利福平不存在药物间的不良交互影响。结论：为临床治疗安全有效地使用利福平和异烟肼提供实验依据。     

Pharmacokinetics of bicyclol in rats with acute hepatic failure

The aim of present study is to evaluate the pharmacokinetics of bicyclol in carbon tetrachloride (CCl(4))-intoxicated rats. The plasma concentration of bicyclol was detected in rats after a single oral or intravenous administration by high-performance liquid chromatography (HPLC) analysis. Rat intestinal and hepatic perfusion models were employed to clarify the respective effect of gut and liver on the pharmacokinetics of bicyclol in acute hepatic failure (AHF) rats. Rat in vitro microsomal incubation was also conducted. The bioavailability of bicyclol was increased 3.1-fold after CCl(4) intoxication in rats. The area under the curve (AUC)((0-infinity)), C(max), and clearance (CL) of bicyclol after intravenous administration were 13.4 mg h l(-1), 18.8 mg l(-1), and 1.8 l h(-1) kg(-1) in control rats, and 130 mg h l(-1), 33.1 mg l(-1), and 0.15 l h(-1) kg(-1) in AHF rats, respectively. In the present study we investigated the pharmacokinetics of bicyclol in CCl(4)-intoxicated rats and differentiated the respective role of intestine and liver by using in situ intestinal and hepatic perfusion in rats, and in vitro rat microsomes incubation. The studies are expected to provide a better understanding related to the alteration of pharmacokinetics of bicyclol in pathological situation.     

Transdermal delivery of isoniazid and rifampin in guinea pigs by electro-phonophoresis

Electro-phonophoresis (EP) has been used as a drug delivery approach in clinical fields. The objective of the present study is to evaluate the skin permeability of isoniazid and rifampin in guinea pigs by EP to provide reference basis for clinical applications of such transdermal delivery system in the treatment of patients with superficial tuberculosis. Isoniazid and rifampin solutions were delivered transdermally with or without EP in health guinea pigs for 0.5?h. Local skin and blood samples were collected serially at 0, 1/2, 1, 2, 4, 6 and 24?h after dosing. Drug concentrations in local skin and blood were evaluated by high-performance liquid chromatography. Isoniazid concentrations in local skin of guinea pigs receiving isoniazid through EP transdermal delivery were significantly higher than in animals receiving only isoniazid with transdermal patch. However, for rifampin, patches alone group presented almost uniform concentration versus time curve with that of EP group, and both groups had concentrations much higher than the therapeutic concentration of the drug over sustainable time. After EP transdermal delivery, the mean peak concentrations of isoniazid and rifampin in skin were 771.0?±?163.4?μg/mL and 81.2?±?17.3?μg/mL respectively. Neither isoniazid nor rifampin concentration in blood could be detected (below the lower detection limit of 1?μg/mL) at any time point. The present study showed that application of EP significantly enhanced INH penetration through skin in guinea pigs, while RIF patch alone obtained therapeutic concentration in local skin. Our work suggests several possible medication approaches for efficient treatment of superficial tuberculosis.     

Pharmacokinetics of bicyclol in rats with acute hepatic failure

The aim of present study is to evaluate the pharmacokinetics of bicyclol in carbon tetrachloride (CCl₄)-intoxicated rats. The plasma concentration of bicyclol was detected in rats after a single oral or intravenous administration by high-performance liquid chromatography (HPLC) analysis. Rat intestinal and hepatic perfusion models were employed to clarify the respective effect of gut and liver on the pharmacokinetics of bicyclol in acute hepatic failure (AHF) rats. Rat in vitro microsomal incubation was also conducted. The bioavailability of bicyclol was increased 3.1-fold after CCl₄ intoxication in rats. The area under the curve (AUC)_(0–∞), C_max, and clearance (CL) of bicyclol after intravenous administration were 13.4 mg h l^?1, 18.8 mg l^?1, and 1.8 l h^?1 kg^?1 in control rats, and 130 mg h l^?1, 33.1 mg l^?1, and 0.15 l h^?1 kg^?1 in AHF rats, respectively. In the present study we investigated the pharmacokinetics of bicyclol in CCl₄-intoxicated rats and differentiated the respective role of intestine and liver by using in situ intestinal and hepatic perfusion in rats, and in vitro rat microsomes incubation. The studies are expected to provide a better understanding related to the alteration of pharmacokinetics of bicyclol in pathological situation.     

异烟肼血药浓度的影响因素分析

目的：分析影响异烟肼血药浓度的因素。方法：对2013年9月~2017年12月的97例异烟肼血药浓度监测患者作回顾性分析,探讨影响异烟肼血药浓度的主要因素。结果：该药血药浓度与体表面积和白蛋白水平存在显著相关性。结论：密切关注具有危险因素患者的血药浓度。     

Effect of rifampin, an inducer of CYP3A and P-glycoprotein, on the pharmacokinetics of risperidone

The authors studied the effect of rifampin, a dual inducer of CYP3A and P-glycoprotein, on the pharmacokinetics and pharmacodynamics of risperidone in humans. Ten healthy male subjects were treated daily for 7 days with 600 mg rifampin or with placebo. On day 6, a single dose of 1 mg risperidone was administered. Plasma risperidone and 9-hydroxyrisperidone concentrations were measured. Rifampin significantly decreased the mean area under the plasma concentration-time curve by 51% for risperidone, by 43% for 9-hydroxyrisperidone, and by 45% for the active moieties (risperidone + 9-hydroxyrisperidone). Rifampin also decreased the peak plasma concentration of risperidone by 38%, 9-hydroxyrisperidone by 46%, and the active moieties by 41%. The apparent oral clearance of risperidone approximately doubled after rifampin treatment. Thus, rifampin reduced the exposure to risperidone, probably because of a decrease in its bioavailability through the induction of CYP3A and probably P-glycoprotein.     

Dual effects of rifampin on the pharmacokinetics of atrasentan

The effect of rifampin, a cytochrome P450 3A4 inducer, on the pharmacokinetics of atrasentan was assessed in 12 healthy male subjects in an open-label study. Single doses of atrasentan 10 mg were administered orally on days 1 and 12. Rifampin 600 mg was given once daily from days 4 through 14. On day 12, atrasentan and rifampin were administered simultaneously. Blood samples were collected before and during 72 hours after each atrasentan dose. On average, rifampin increased atrasentan peak plasma concentrations by 150% and reduced its terminal half-life by 77% (P<.05), without affecting the AUC or peak time of atrasentan. Rifampin may affect atrasentan pharmacokinetics by acting as both an inhibitor of organic anion transporting polypeptide-mediated hepatic uptake of atrasentan and an inducer of atrasentan metabolism. The effect of rifampin on atrasentan pharmacokinetics may depend on the time of rifampin administration relative to that of atrasentan.     

Saliva and plasma concentrations of isoniazid and acetylisoniazid in man.

1. The pharmacokinetics of isoniazid and acetylisoniazid in plasma and saliva were compared following administration of oral and intravenous doses (200 mg) to healthy volunteers and patients. 2. In the 22 subjects studied after oral administration and the six subjects studied after intravenous administration there was complete phenotypic agreement for both slow (t1/2 greater than 130 min) and fast (t1/2 less than 130 min) acetylators using either saliva or plasma. 3. Acetylator phenotyping based on the t1/2 of INH determined using saliva collected at 2, 3, 4, 5 and 6 h after a 200 mg oral dose appears to be as reliable as that based on plasma. 4. Salivary isoniazid concentrations may provide a non-invasive alternative to plasma concentrations.