甲磺酸帕珠沙星与其它抗生素联用于大鼠模型的药动学研究

目的:对甲磺酸帕珠沙星与其它抗生素联合应用的大鼠药代动力学进行对比研究,评价药物间的相互作用及联合用药的合理性.方法:采用一个剂量组,3种用药方案分别单次给药.用药方案:帕珠沙星45 mg/kg;帕珠沙星45 mg/kg加头孢哌酮/舒巴坦180 mg/kg;帕珠沙星45 mg/kg加阿奇霉素45 mg/kg.采用反相HPLC-UV法测定大鼠血药浓度,用DAS软件估算药动学参数,进行统计学分析及临床药效评价.结果:甲磺酸帕珠沙星单用及与头孢哌酮/舒巴坦或阿奇霉素联用的主要药动学参数t1/2、Cmax、tmax、AUC无显著性差异,但帕珠沙星与阿奇霉素联用后清除率(CL)降低及体内驻留时间(MRT)延长,具有统计学意义.结论:帕珠沙星与头孢哌酮/舒巴坦,帕珠沙星与阿奇霉素联用是可行的用药方案.     

哌拉西林钠对甲磺酸帕珠沙星在大鼠体内药代动力学的影响

目的研究哌拉西林钠对甲磺酸帕珠沙星在大鼠体内药代动力学的影响。方法 12只健康雄性SD大鼠随机分成2组(分别为单独和联合给药组),用HPLC法测定血浆中甲磺酸帕珠沙星的浓度。结果单独用药与联合用药组ρmax分别为(33.54±4.68)和(37.83±3.43)mg.L-1,AUC0-t分别为(43.32±15.91)和(41.98±9.19)mg.h.L-1,t1/2分别为(1.00±0.31)和(0.80±0.24)h,无显著性差异(P>0.05)。结论与哌拉西林钠联合用药后甲磺酸帕珠沙星在大鼠体内的药动学参数均不存在显著性差异。     

Comparative pharmacokinetics of cefoperazone and cephradine in untreated streptozotocin diabetic rats.

Experimental diabetes mellitus was induced in adult male rats by injecting streptozotocin (STZ; 60 mg/kg iv) for the purpose of surveying changes in the pharmacokinetics of biliary excretion after the intravenous administration of 40 mg/kg of cefoperazone (CPZ) or cephradine (CED). CPZ, CED, and other organic anions share affinity for the organic anion transport system in the bile canalicular membrane. The STZ treatment had a marked influence on the distribution and elimination of both cephalosporins. The blood levels of both cephalosporins at each time point after administration differed significantly between the STZ-treated and control rats. The values of mean residence time (MRT) of CPZ and CED were significantly decreased in the STZ-treated rats. Basal bile flow rates were increased after the administration of CPZ in the control and STZ-treated rats. Biliary clearance (CLbile) of CPZ was more than 60% of the CLtot, whereas CLbile of CED was less than 20% of CLtot in both groups of rats. The mean CLbile value of CPZ in the STZ-treated rats was 1.0 ml/min higher than that of the control rats, whereas the mean CLbile value of CED was almost the same as that of the control rats. The increased CLbile of CPZ suggested that diabetes alters the biliary excretion of CPZ. The changes in MRT of CPZ in the STZ-treated and control rats are mainly caused by an increase in the biliary excretory rate and renal clearance. The changes in MRT of CED in the STZ-treated and control rats are caused by a decrease in the apparent volume of distribution and increased renal clearance.     

Influence of famotidine on verapamil pharmacokinetics in rats.

The effect of famotidine (4 mg/kg, p.o.) on the kinetic profile of co-administered verapamil (20 mg/kg(-1), p.o.) was studied in the rat. Plasma verapamil levels were collected serially for 12 h and measured using sensitive HPLC method. The pharmacokinetic parameters (elimination half-life, area under the plasma concentration-time curve, peak plasma levels and the times to attain these plasma levels) of verapamil were evaluated in the rat. The results indicate that co-administered famotidine did not significantly alter the pharmacokinetic profile of verapamil in the rat. The present finding suggests that famotidine may safely be co-administered with verapamil but clearly further studies in human subjects are needed to reliably rule out the potential interaction of these two drugs.     

The effect of azithromycin on the pharmacokinetics of indinavir.

This study was performed to examine the effect of the coadministration of azithromycin on the pharmacokinetics of the protease inhibitor indinavir (Crixivan). In an open-label, parallel-design study, 32 healthy male and female volunteers were given indinavir (800 mg tid) for 5 days. One hour prior to the first dose of indinavir on day 5, 18 subjects received 1200 mg azithromycin (Zithromax), and 14 subjects received matching placebo. Serial samples of plasma were obtained for 8 hours following the morning dose of indinavir on days 4 and 5 and assayed for indinavir by HPLC/UV. Twenty-seven subjects completed the study. Following coadministration of azithromycin with indinavir, there was no significant change between day 5 and day 4 in AUC (20.7 mg.hr/ml and 23.1 mg.hr/ml; 90% CI on the ratio 81%-100%) or Cmax (9.88 mg/ml and 10.3 mg/ml; 90% CI 86%-108%). The day 5 to day 4 difference in indinavir concentrations following coadministration with azithromycin was not significantly different from the day 5 to day 4 difference with placebo (AUC p = 0.68; Cmax p = 0.074). Therefore, azithromycin does not significantly alter the kinetics of indinavir.     

甲磺酸帕珠沙星注射液人体药动学研究

目的研究单次及多次静脉滴注甲磺酸帕珠沙星注射液的药动学特点。方法筛选健康受试者12名,q12h静脉滴注甲磺酸帕珠沙星注射液每次500m g,连续5d,共9次;用反向高效液相色谱-紫外法测定血药浓度,用DA Sver1.0软件拟合药动学参数。结果受试者静脉滴注甲磺酸帕珠沙星注射液后体内过程符合二室模型;单次给药后的药动学参数:Tm ax为(0.47±0.09)h,cm ax为(13.71±1.81)m g/L,AUC0-t为(24.60±4.15)m g.h/L,t1/2为(1.46±0.64)h,M RT、CL和Vd分别为(2.14±0.33)h、(0.09±0.04)L/(h.kg)和(0.17±0.03)L/kg。q12h静脉滴注帕珠沙星500m g连续5d(共9次),第2、3、4、5d晨测得谷浓度分别为0.13、0.16、0.17和0.14m g/L,提示血药浓度已达稳态。末剂给药后的药动学参数:Tm ax为(0.48±0.10)h,cm ax为(15.41±1.67)m g/L,AUC0-t为(28.42±4.90)m g.h/L,t1/2为(1.33±0.49)h,CL为(0.09±0.06L/)h,(css)av为(2.34±0.43)m g/L,DF为(99.48±0.38)%,以上参数与单次给药比较除cm ax外均无统计学差异,且累积系数小,说明本品多次给药无体内蓄积。女性和男性受试者主要药动学参数比较均无统计学差异。受试者给药期间未出现严重不良反应。结论500m g q12h静脉滴注,在人体内可达到有效血药浓度,可以作为临床应用的推荐方案。     

烫伤对头孢哌酮药物动力学的影响

目的：研究烫伤对头孢哌酮药物动力学的影响。方法：利用ＨＰＬＣ法测定头孢哌酮血药浓度并对８只家兔烫伤前后头孢哌酮药动学进行研究。结果：该药静脉注射给药后药动学符合二室开放模型。烫伤对头孢哌酮药动学有显著影响，烫伤前Ｔ１／２为１．２６±０．１４ｈ，Ｖｄ为０．４２±０．１８Ｌ·ｋｇ－１，烫伤后Ｔ１／２比烫伤前延长，为２．１４±０．３６ｈ（Ｐ＜０．０１），Ｖｄ增加，为０．６４±０．２１Ｌ·ｋｇ－１（Ｐ＜０．０１）。结论：烫伤病人在用药时需考虑烫伤引起的药动学改变     

Azithromycin临床药物动力学研究

对１０名健康志愿者口服ａｚｉｔｈｒｏｍｙｃｉｎ的药物动力学研究以及其干糖粉的相对生物利用度测定结果显示：空腹口服ａｚｉｔｈｒｏｍｙｃｉｎ单剂５００ｍｇ后，其体内过程符合二室模型，其消除半衰期为５０．３９±８．８７ｈ；高峰血浓度为０．４０３±０．２９９ｍｇ／Ｌ；达峰时间为２．６４±１．２６ｈ，ＡＵＣ为６．３９±１．８１ｈｍｇ／Ｌ。１４４ｈ累积尿排出率为１１．５２％±２．７０％。干糖粉与胶囊比较的相对生物利用度为１１０．６％。根据其药物动力学参数和抗微生物活性，给予针对不同感染的治疗方案     

健康老年肾对头孢哌酮/舒巴坦(1:1)药代动力学的影响

目的 观察随年龄增长所致的肾功能减退对头孢哌酮(CFZ,第 3 代头孢类抗生素)/舒巴坦(SBT,β内酰胺酶抑制剂)药代动力学的影响.方法 44 名健康成年与老年受试者,每 12 h 静脉给予 CFZ/SBT 各1g,共7次,采集末次给药后不同时间的血样,用 HPLC 方法测定血药浓度;肌酐清除率(Ccr)用 Cockcrofi and Gault 法计算.结果 老年男性和成年男性 Ccr 分别为(65.3±7.7),(106.0±21.6)mL·min-1(P＜0.01);稳态时,CFZ:AUC 分别为(256.3±72.0),(182.3±49.6)mg·h·L-1(P＜0.01);Cmax 分别为(102.0±15.3),(89.4±10.7)μg·mL-1(P＜0.05);t1/2 分别为(2.2±0.6),(1.5±0.5)h(P＜0.01);CLT 分别为(4.2±1.2),(5.8±1.2)L·h-1(P＜0.01),Ccr与CLT、AUC、t1/2相关(γ分别为0.52、-0.40、-0.27,均P＜0.01).稳态时,SBT:AUC 分别为(81.8±28.4),(33.7±6.7)mg·h·L-1(P＜0.01);Cmax 分别为(54.7±19.9),(28.0±4.8)μg·mL-1(P＜0.01);t1/2分别为(1.4±0.4),(1.1±0.5)h(P>0.05);CLT 分别为(13.7±4.9),(30.6±5.2)L·h-1(P＜0.01),Ccr与CLT、AUC、t1/2相关(γ分别为0.52、-0.44、-0.47,均P＜0.01).两药的CLT比值:SBT/CFZ分别为(3.43±1.42),(5.52±1.52)(P＜0.01).说明老年人对 CFZ/SBT 清除下降,以 SBT 为显著.结论 老年的肾功能轻度减退,可造成 CFZ/SBT 药代动力学改变,SBT 更明显.     

Influence of andrographolide on the pharmacokinetics of warfarin in rats

Context: Andrographolide and warfarin are often used together in clinics in China. However, the herb-drug interaction between andrographolide and warfarin is still unknown.

Objective: This study investigates the herb-drug interaction between andrographolide and warfarin in vivo and in vitro.

Materials and methods: A sensitive and reliable LC-MS/MS method was developed for the determination of warfarin in male Sprague-Dawley rats plasma, and then the pharmacokinetics of orally administered warfarin (0.5?mg/kg) with or without andrographolide (30?mg/kg/day for 7?days) pretreatment was investigated. In addition, Sprague-Dawley rat liver microsomes incubation systems were used to support the in vivo pharmacokinetic data and investigate its potential mechanism.

Results: The method validation results showed that a sensitive and reliable LC-MS/MS method was developed for the determination of warfarin in rat plasma samples. The pharmacokinetic results indicated that co-administration of andrographolide could increase the systemic exposure of warfarin significantly, including area under the curve (118.92?±?18.08 vs. 60.58?±?9.46?μg?×?h/mL), maximum plasma concentration (3.32?±?0.41 vs. 2.35?±?0.25?μg/mL) and t_1/2 (22.73?±?3.28 vs. 14.27?±?2.67?h). Additionally, the metabolic stability of warfarin increased from 23.5?±?4.7 to 38.7?±?6.1?min with the pretreatment of andrographolide, and the difference was significant (p?Discussion and conclusion: In conclusion, andrographolide could increase the systemic exposure of warfarin in rats when andrographolide and warfarin were co-administered, and possibly by slowing down the metabolism of warfarin in rat liver by inhibiting the activity of CYP3A4 or CYP2C9.     

Influence of glycerol-induced acute renal failure on the pharmacokinetics of cyclosporin in rats.

Although it is widely believed that renal dysfunction has no effect on the pharmacokinetics of cyclosporin, many clinical reports suggest that renal dysfunction after renal transplantation is closely related to the pharmacokinetics of cyclosporin. To clarify the relationship between renal dysfunction and the pharmacokinetics of cyclosporin, we examined the influence of acute renal failure (ARF) on its pharmacokinetics in glycerol-induced ARF rats. The values of indicators of renal function (serum creatinine, blood urea nitrogen), but not those of indicators of hepatic function, were significantly increased in ARF rats that received glycerol compared with values for control rats. The area under the blood cyclosporin concentration-time curve after oral administration (AUCpo) were 4.976+/-0.847 mghL(-1) for ARF rats and 9.684+/-1.100 mghL(-1) for control rats; AUCpo in ARF was significantly reduced in a manner dependent on renal function. The oral clearance of cyclosporin in ARF and control rats was 1.172+/-0.207 and 0.544+/-0.062Lh(-1) kg(-1), respectively, whereas total body clearance in ARF and control rats was 0.151+/-0.008 and 0.183+/-0.010Lh(-1)kg(-1), respectively. The relative bioavailability of cyclosporin in ARF and control rats was 0.118 and 0.336, respectively. In an in-vitro study using everted sac and liver-slice methods, the apparent first-order rate constants for cyclosporin uptake (k(uptake)) and metabolism (k(metab)) in gut tissues were reduced, whereas k(uptake) and k(metab) in liver were increased. Gastric emptying, measured by use of paracetamol, was significantly reduced in ARF rats. These results suggest that glycerol-induced ARF results in several changes in the pharmacokinetics of cyclosporin in rats. From these results, we conclude that reduction of the absorbed fraction of cyclosporin strongly contributes to the decrease in AUCpo in the presence of ARF.     

兔眼结膜中阿奇霉素的浓度测定及其药动学

目的建立兔眼结膜中阿奇霉素的LC-MS/MS检测方法,研究阿奇霉素滴眼液在兔眼结膜中的药动学特征。方法 184只新西兰白兔进行单次以及多次给阿奇霉素滴眼液后,于不同时间点取眼结膜样本匀浆处理后以沉淀法去除匀浆液中蛋白基质,采用LC-MS/MS法测定兔眼结膜中的阿奇霉素。以克拉霉素为内标,采用Ultimate XB-Phenyl(100 mm×3.0 mm,3μm)色谱柱,流动相为乙腈-0.01 mol.L-1乙酸铵水溶液(含0.1%乙酸)(75∶25,V/V),电喷雾离子源,正离子SRM扫描分析,内标和阿奇霉素离子对分别为:m/z 748→m/z 590和m/z 749→m/z 591。结果阿奇霉素结膜浓度在10.128～8 102.4μg.L-1范围内线性关系良好(r=0.998 7);最低定量限为10.128μg.L-1;批内和批间RSD均小于10%;方法准确度在85%～115%之间。单次给药后参比制剂和受试制剂的药动学参数tmax分别为2 h和2 h,ρmax分别为22.29μg.g-1和21.80μg.g-1,AUC1-192分别为528.0μg.h.g-1和536.5μg.h.g-1,t1/2分别为25.5 h和24.1 h。多次给药后参比制剂和受试制剂的药动学参数tmax分别为8 h和8 h,ρmax分别为53.10μg.g-1和51.62μg.g-1,AUC1-192分别为1 584.9μg.h.g-1和1 379.4μg.h.g-1,t1/2分别为28.8 h和23.7 h。受试制剂和参比制剂药动学行为基本一致。结论建立的检测方法简便、灵敏。多次给药后在兔眼结膜内存在蓄积现象。     

Influence of hepatic regeneration after partial hepatectomy on theophylline pharmacokinetics in rats.

The influence of hepatic regeneration after partial hepatectomy on theophylline pharmacokinetics has been studied on the rat. At different times after partial hepatectomy, theophylline was administered intravenously as a single dose of 6 mg/Kg. Drug plasma levels were determined by HPLC and pharmacokinetic parameters were obtained. Physiological parameters were also measured. Following hepatectomy, an increase in mass liver was observed and 15 days after surgery, liver mass was 78% of nonhepatectomized rats. Initial theophylline concentrations varied during the regeneration period, as well as the distribution volume at steady-estate (Vss). Elimination half-life (t 1/2), notably increased after hepatectomy (7.27+/-1.38 h), decreased with time (6.70+/-1.18 h, 6.47+/-0.69 and 5.17+/-0.87 h after 24 h, 3 days and 15 days post-hepatectomy, respectively) to reach a value close to that of the control group (4.30+/-1.37 h). The increase in elimination half-life led to a decrease in the mean residence time during the period of liver regeneration. However, the intrinsic clearance hardly varied during regeneration period. We could establish the following relationship between liver weight (LW) and the elimination half-life: t 1/2 (h)=-0.358*LW (g)+8.6168 (R2=0.9906). For the mean residence time (MRT) this relationship was: MRT (h) =-0.5173*LW (g)+12.433 (R2=0.991).     

阿奇霉素健康人体药物动力学及相对生物利用度研究

目的：研究阿奇霉素分散片健康人体药物动力学及相对生物利用度。方法：采用微生物法测定８名志愿者单剂量口服１０００ｍｇ阿奇霉素分散片和胶囊后不同时间血清和尿中药物浓度。结果：阿奇霉素分散片和胶囊的血药浓度－时间曲线均符合二室模型，比较两种制剂的药动学参数及１９２ｈ尿中总排泄率差异均无显著性。结论：阿奇霉素分散片的相对生物利用度为１０３．１％±１０．５％，两种制剂生物等效     

艾迪注射液对大鼠体内紫杉醇药代动力学的影响

目的:研究艾迪注射液对大鼠体内紫杉醇药代动力学参数的影响。方法:12只SD大鼠,雌雄各半,体重180~220 g,随机分为对照组和实验组,实验组连续5 d给予艾迪注射液1 mL·kg~(-1),每天1次,对照组给予等量生理盐水代替。最后一次给药后30 min两组均给予紫杉醇注射液12 mL·kg~(-1),并于给药后0、0.5、1、2、4、8、12、24和48 h分别自眼眶取血0.2 mL。分离血浆后采用液质联用的方法测定血浆中紫杉醇的含量,采用DAS2.0软件分析药代动力学参数,采用SPSS软件进行统计学分析。结果:对照组和实验组的C_(max)分别为(39 555.69±1 728.70)和(79 957.62±18 067.58)μg·L~(-1)(P<0.05);AUC_(0→t)分别为(28 616.24±7 059.78)和(76 066.42±32 518.88)μg·L~(-1)·h(P<0.05);t_(1/2)分别为(3.49±1.17)和(5.99±0.75)h(P<0.05);其他参数差异无显著性。结论:艾迪注射液可显著增加大鼠体内紫杉醇的C_(max)和AUC_(0→t)并降低t_(1/2)。     

Influence of ABCB1 gene polymorphisms on the pharmacokinetics of azithromycin among healthy Chinese Han ethnic subjects

The aim of this study was to evaluate the effects of ABCB1 gene polymorphisms on azithromycin pharmacokinetics in Chinese Han ethnic subjects. In total, 20 healthy volunteers with various ABCB1 genotypes (6 with 2677GG/3435CC, 8 with 2677GT/3435CT, 6 with 2677TT/3435TT) were enrolled. Each was given a single oral dose of 500 mg azithromycin. Plasma concentration was measured for up to 96 h by LC/MS/MS. As shown, C_max was significantly lower among individuals with 2677TT/3435TT genotype (468.0 ± 173.4 ng ? h/ml) than those with 2677GG/3435CC (911.2 ± 396.4 ng ? h/ml, p = 0.013). However, the t_max value was higher among subjects with 2677TT/3435TT (2.0 ± 0.5 h) than those with 2677GT/3435CT (1.6 ± 0.3 h) or 2677GG/3435CC (1.4 ± 0.4 h) genotypes (p = 0.068 and p = 0.026, respectively). Furthermore, the AUC _last tended to be higher among subjects with 2677GG/3435CC than those with 2677GT/3435CT or 2677TT/3435TT genotypes (5000.2 ± 1610.0 vs. 4558.0 ± 805.0 vs. 4131.0 ± 995.1 ng/ml). Our results showed for the first time that azithromycin pharmacokinetics may be influenced by particular polymorphisms of the ABCB1 gene. Individualized dosage regimen design incorporating such information may improve the efficacy of the drug while reducing adverse reactions.     

Influence of streptozotocin-diabetes on the pharmacokinetics, placental transfer and tissue localization of dexamethasone in rats.

The influence of streptozotocin-diabetes on the pharmacokinetics, placental transfer and tissue localization of dexamethasone was determined in Sprague-Dawley rats. Diabetes significantly increased the volume of distribution of dexamethasone in pregnant but not in nonpregnant rats; plasma half-life was not significantly increased. Concentrations of maternally administered dexamethasone in all tissues studied (maternal and foetal serum and livers, foetal lungs and placentas) except the amniotic fluid were lower in diabetic than in control animals. Diabetes did not alter the binding of dexamethasone to maternal or foetal serum proteins. Insulin treatment partially reversed the effects of diabetes on the maternal-foetal exchange of dexamethasone. Diabetes-induced decrease in the foetal localization of dexamethasone appears to be caused by a decrease in the maternal serum levels as well as by an increase in the foetal excretion of the steroid into the amniotic fluid. In so far as the rat model reflects the human situation, the present data suggest that a standard dose of dexamethasone might not be adequate in promoting foetal lung maturation in diabetic pregnancies.     

Influence of dietary manganese on the pharmacokinetics of inhaled manganese sulfate in male CD rats.

Concerns exist as to whether individuals with relative manganese deficiency or excess may be at increased risk for manganese toxicity following inhalation exposure. The objective of this study was to determine whether manganese body burden influences the pharmacokinetics of inhaled manganese sulfate (MnSO(4)). Postnatal day (PND) 10 rats were placed on either a low (2 ppm), sufficient (10 ppm), or high (100 ppm) manganese diet. The feeding of the 2 ppm manganese diet was associated with a number of effects, including reduced body weight gain, decreased liver manganese concentrations, and reduced whole-body manganese clearance rates. Beginning on PND 77 +/- 2, male littermates were exposed 6 h/day for 14 consecutive days to 0, 0.092, or 0.92 mg MnSO(4)/m(3). End-of-exposure tissue manganese concentrations and whole-body (54)Mn elimination rates were determined. Male rats exposed to 0.092 mg MnSO(4)/m(3) had elevated lung manganese concentrations when compared to air-exposed male rats. Male rats exposed to 0.92 mg MnSO(4)/m(3) developed increased striatal, lung, and bile manganese concentrations when compared to air-exposed male rats. There were no significant interactions between the concentration of inhaled MnSO(4) and dietary manganese level on tissue manganese concentrations. Rats exposed to 0.92 mg MnSO(4)/m(3) also had increased (54)Mn clearance rates and shorter initial phase elimination half-lives when compared with air-exposed control rats. These results suggest that, marginally manganese-deficient animals exposed to high levels of inhaled manganese compensate by increasing biliary manganese excretion. Therefore, they do not appear to be at increased risk for elevated brain manganese concentrations.     

Influence of spironolactone pretreatment on pharmacokinetics and metabolism of digitoxin in rats

Summary The influence of pretreatment with spironolactone (84 mg/kg at 3 days, twice per day) on the tritium levels in plasma, urine and feces of female SD-rats (n=9) was investigated at various time periods after oral administration of 25 g/kg ³H-digitoxin. In plasma, the concentrations of total radioactivity are reduced in pretreated animals to about 20% of tritium levels in control rats, while the half-life of radioactivity in both groups is almost identical, 2.9 days in pretreated rats and 2.8 days in controls. The lower plasma levels of tritium in pretreated rats coincide with a six-fold decrease in the urinary ³H-elimination and a corresponding increase in the fecal excretion. This is due to a higher biliary clearance of tritiated products in the early phase of elimination. The separation of the excretion products by TLC shows that spironolactone pretreatment enhances the splitting of the glycosidic bonds of digitoxin. The amount of digitoxigenin-bis-digitoxoside and of digitoxigenin-mono-digitoxoside excreted in urine and feces within 96 hrs is four and ten times greater than that recovered in control animals, respectively. The formation of the hydroxylation products digoxin and digoxigenin-bis-digitoxoside is decreased from 50% of the total excreted radioactivity in control to 15% in pretreated rats. The conjugation reactions with glucuronic and sulfuric acid are increased after pretreatment with spironolactone. Thus, the effect of spironolactone on digitoxin kinetics is apparently related to an enhancement of the hepatic excretory mechanism as well as to an enhanced metabolism.Supported by the Deutsche Forschungsgemeinschaft.     

吲达帕胺对大鼠替米沙坦药代动力学的影响及性别差异(英文)

目的研究吲达帕胺对雌性和雄性大鼠替米沙坦药代动力学的影响。方法Wistar大鼠随机分为替米沙坦单用和替米沙坦与吲哒帕胺联用组,雌雄各半,分别单次ig给予替米沙坦3.6mg·kg-1或替米沙坦3.6mg·kg-1+吲达帕胺0.135mg·kg-1。96h内定时取血后,采用反相高效液相色谱-荧光检测法测定血浆中替米沙坦浓度。结果无论雄性雌性大鼠,与替米沙坦单用组相比,联用吲达帕胺后替米沙坦的主要药代动力学参数无显著性改变;而不同性别大鼠替米沙坦的药代动力学有显著差异,无论替米沙坦单用或联用吲达帕胺组,雌性大鼠替米沙坦的主要药代动力学参数AUC和cmax值均显著高于雄性,而血浆清除率显著低于雄性。结论替米沙坦与吲达帕胺联用对大鼠替米沙坦的药代动力学无明显影响;而无论替米沙坦单用或联用吲达帕胺,雌性和雄性大鼠替米沙坦的药代动力学存在显著的性别差异。