乙酰唑胺对表达水孔蛋白1的非洲爪蟾卵母细胞转运水功能的影响

目的观察乙酰唑胺对水孔蛋白1(AQP1)水转运功能的影响。方法将AQP1 cRNA 10 ng注射入非洲爪蟾卵母细胞,观察并记录给予1×10^-7～1×10^-5 mol·L^-1乙酰唑胺后卵母细胞在低渗溶液中的膨胀率,并计算其渗透水通透性(Pf)的变化。结果非洲爪蟾卵母细胞表达AQP1蛋白后,在低渗溶液中迅速膨胀,Pf值显著增加至1.82×10^-2 cm·s^-1,而注射水的阴性对照仅为0.25×10^-2 cm·s^-1。AQP抑制剂HgCl₂使Pf值降至0.64×10^-2 cm·s^-1;1×10^-7～1×10^-5 mol·L^-1乙酰唑胺处理后,Pf值分别降至1.43,1.24和0.93×10^-2 cm·s^-1。结论乙酰唑胺剂量依赖性地降低AQP1介导的渗透水通透性,抑制AQP1转运水的功能。     

西红花苷对牛主动脉平滑肌细胞内钙离子浓度的影响

目的研究西红花苷对血管平滑肌细胞内钙离子浓度的影响。方法以Fluo-3/AM作为Ca²⁺荧光探针,采用激光扫描共聚焦显微镜观察牛主动脉平滑肌细胞内钙离子浓度的变化。结果无论细胞外有无钙离子,西红花苷(1×10^-8,1×10^-7,1×10^-6 mol·L^-1)均能明显抑制1×10^-2 mol·L^-1 H₂O₂引起的细胞内钙离子浓度的升高,其抑制率含钙条件下分别为34.1%, 57.1%和74.3%(P<0.01),无钙条件下分别为26.2%,32.1%和50.0%(P<0.01);在胞外无钙的条件下,西红花苷 (1×10^-8,1×10^-7,1×10^-6 mol·L^-1)能抑制70 mmol·L^-1 CHCl₃导致雷洛丁敏感钙池的释放,其抑制率分别为27.8%, 27.8%和50.0% (P<0.01)。结论西红花苷能抑制胞外钙离子的内流及内质网上钙离子的释放。     

某些四氢异喹啉类生物碱对大鼠脑内多巴胺和5-羟色胺受体的作用

本文报道十二种四氢异喹啉类生物碱对大鼠脑内D-2,5-HT₁和5-HT₂受体的结合特性。其中l-千金藤碱(l-STP)对这三种受体均有较高的亲和力,其Ki值分别为1.7×10^-7,9.4×10^-8和1.8×10^-7mol。l-莲碱(l-REM)对5-HT₂受体的亲和力与Z-STP相似(Ki=1.7×10^-7mol)。THB,THC和THJ对D-2受体的亲和力介于l-SPD和l-THP之间。本文报道的多数生物碱能同时影响两种或两种以上受体部位的结合特性,提示它们对单胺神经系统可能有复杂的相互作用。     

黄芪甲苷和齐墩果酸对体外神经干细胞增殖和Jagged1 mRNA表达的影响

目的 观察黄芪甲苷和齐墩果酸对体外神经干细胞增殖和相关基因Jagged1表达的影响。方法 采用机械吹打法从胎鼠脑内获得神经干细胞,随机分组,分别给予不同浓度(10^-6,5×10^-7,10^-7,5×10^-8,10^-8,5×10^-9,10^-9 mol·L^-1)的黄芪甲苷、齐墩果酸进行干预,72 h后用WST法检测细胞的增殖情况,PCR检测Jagged1表达水平。结果 黄芪甲苷对体外神经干细胞增殖影响不显著,高剂量尚存在细胞毒性。齐墩果酸能促进神经干细胞增殖,且呈一定的剂量效应关系,与对照组和黄芪甲苷组比较均有显著差异(P<0.05)。细胞未分化状态下Jagged1基因存在一定的表达,增殖率越高Jagged1表达水平越高;与同浓度黄芪甲苷组比较,齐墩果酸显著上调Jagged1表达(P<0.05)。结论 不同浓度的黄芪甲苷和齐墩果酸对体外培养神经干细胞增殖和Jagged1表达的影响不同;齐墩果酸作用优于黄芪甲苷。     

离子导入对降纤酶经皮渗透的影响

目的研究离子导入对降纤酶经皮渗透的影响。方法利用水平式扩散池，对降纤酶进行离子导入透过大鼠皮肤和人尸表皮的渗透性试验，对电极极性、渗透介质的pH以及离子强度等影响进行考察。结果离子导入阳极转运时，在pH 6.4的磷酸盐缓冲介质中，降纤酶的表观经皮渗透系数为（1.2±0.4）×10^-4 cm·h^-1，明显高于阴极转运［（4.3±1.4）×10^-5 cm·h^-1］；在pH 7.4磷酸盐缓冲介质中，降纤酶阳极离子导入经皮渗透量为（25±5）×10^-14 mol·cm^-2高于pH 6.4介质经皮渗透量［(15±4)×10^-14 mol·cm^-2］。结论离子导入阳极转运能够促进降纤酶的经皮渗透，电渗作用有重要影响。     

魔芋葡甘聚糖分子链形态及链参数研究魔芋葡甘聚糖分子链形态及链参数研究

目的研究魔芋葡甘聚糖分子链形态，测定分子链参数。方法采用光散射、凝胶渗透色谱及粘度法测定溶液行为；采用原子力显微镜及透射电镜直接观测分子形貌。结果魔芋葡甘聚糖重均分子量M_w、均方根旋转半径〈S₂〉^1/2以及第二维利系数A₂分别为1.04×10⁶, (105.0±0.9) nm,和 (-1.59±0.28)×10^-3 mol·mL·g^-2，多分散系数M_w/M_n为1.02，Mark-Houwink方程为［η］=5.96×10^-2M^0.73_w；分子链参数M_L=982.82 nm^-1,q=27.93 nm, d=0.74 nm,h=0.26 nm,L=1 054.11 nm。结论直接观察到的分子形貌和根据溶液行为的推测均说明，魔芋葡甘聚糖为伸展的有一定刚性的半屈曲性直链分子，不存在支链。     

拉氧头孢钠的极谱行为及其痕量测定方法

在HCI-KCI（ｐＨ1～2）介质中，用循环伏安和示差脉冲极谱（ＤＰＰ）等电化学方法研究了拉氧头孢钠（噻吗灵）的电极反应机理，并建立了用ＤＰＰ测定的新方法。其峰电位为-0.62V（ｖｓＡｇ/ＡｇＣｌ），峰电流与拉氧头孢钠浓度在1×10^-8～5×10^-6ｍｏｌ·Ｌ^-1（富集时间t_ac＝９０ｓ），5×10^-6～5×10^-5ｍｏｌ·Ｌ^-1（t_ac＝７０ｓ），5×10^-5～８×１０^-4ｍｏｌ·Ｌ^-1（t_ac＝30ｓ）范围内成线性关系。检测限为４×１０^-9ｍｏｌ·Ｌ^-1（t_ac＝９０ｓ）。本法可用于注射剂中该物质的测定，同时也探讨了直接测定尿中拉氧头孢钠的可能性。     

利用人源Caco-2细胞单层模型研究罂粟碱、N-甲基四氢罂粟碱和头花千金藤碱在人肠道的吸收

研究罂粟碱(papaverine，PAP)、N-甲基四氢罂粟碱(laudanosine，LAU)和头花千金藤碱(cepharanthine，CEP)在人小肠的吸收。利用人源结肠腺癌细胞系Caco-2细胞单层模型研究PAP、LAU和CEP由绒毛面(AP侧)到基底面(BL侧)、BL侧到AP侧两个方向的转运过程。应用HPLC-UV对上述3个生物碱进行定量分析，计算转运参数和表观渗透系数，并与易吸收性对照药普萘洛尔和难吸收性对照药阿替洛尔进行比较。PAP、LAU和CEP由AP侧到BL侧的表观渗透系数(P_app)分别为(3.524±0.223)×10^-5、(2.821±0.050)×10^-5和(6.524±0.052)×10^-5 cm·s^-1；由BL侧到AP侧的P_app分别为(5.095±0.508)×10^-5、(2.646±0.146)×10^-5和(5.495±0.036)×10^-5 cm·s^-1，与在Caco-2细胞单层模型上呈良好吸收的阳性对照药普萘洛尔基本一致。PAP、LAU和CEP的P_{app A→B}/P_{app B→A}分别为0.69、1.07和1.19；PAP外流是摄取的1.45倍。PAP、LAU和CEP可以通过小肠上皮细胞被动吸收进入体内，属于良好吸收的药物。在三者的吸收转运过程中，油/水分配系数起着关键性的作用。PAP在Caco-2细胞单层模型中的转运可能存在外流机制。     

奥美拉唑的吸附伏安特性及其应用

目的研究奥美拉唑(omeprazole,OPZ)的电化学行为,拟定测定OPZ的吸附溶出伏安法。方法用单扫示波极谱法、循环伏安法等技术进行研究。结果在0.1mol·L^-1NH₃-NH₄Cl(pH8.90)底液中,OPZ在汞电极上有一线性扫描还原峰,其峰电位E_p=-1.04V(vs Ag/AgCl),该峰有明显的吸附性。吸附粒子为OPZ中性分子,测得OPZ在汞电极上的饱和吸附量Γ_s=9.55×10^-11mol·cm^-2,每个OPZ分子所占电极面积为1.74nm²,OPZ在汞电极上的吸附符合Frumkin吸附等温式。测得吸附系数β=1.32×10⁶,25℃时的吸附自由能ΔGθ=-34.93kJ·mol^-1,电极反应电子数n=4,不可逆体系动力学参数αn_α=0.78,表面电极反应速率常数k_s=0.18s^-1,OPZ在溶液中的扩散系数D=1.03×10^-5cm²*s^-1。建立了吸附溶出伏安法测定OPZ的最佳条件,检出限为2.0×10^-9mol·L^-1。结论证实该体系为具有吸附性的不可逆过程。     

水飞蓟素微乳大鼠在体小肠吸收的动力学

目的考察水飞蓟素微乳的形态学和粒径分布，研究水飞蓟素微乳在小肠各部位的吸收情况，并与水飞蓟素胶束在空肠的吸收进行比较。方法采用大鼠在体小肠段回流实验，紫外分光光度法测定药物浓度，依据药物在小肠段中的减少量来确定药物的吸收。结果透射电镜下水飞蓟素微乳成球形或近球形，大小均匀，平均粒径约为20 nm。在整个小肠、回肠、空肠、十二指肠以及结肠中的吸收速率常数依次是6.22×10^-2,2.27×10^-2,1.9×10^-2,1.05×10^-2,0.43×10^-2 h^-1，两种水飞蓟素胶束在空肠的吸收速率常数分别是0.36×10^-2,0.65×10^-2 h^-1。结论水飞蓟素微乳在小肠下段吸收较好，吸收呈一级动力学过程，吸收机制为被动扩散。     

Glucose Partition Coefficient and Diffusivity in the Lower Skin Layers

Purpose This work aims to estimate the diffusivity and partitioning of glucose in the dermis and the viable epidermis of human skin. Methods The partition coefficient of glucose between phosphate-buffered saline and dermis, tape-stripped epidermis (TSE), stratum corneum (SC), and split-thickness skin, was measured in vitro using human cadaver skin. Glucose permeability across dermis and tape-stripped split-thickness skin (TSS) was measured using side-by-side diffusion cells. Glucose desorption from TSE and human epidermal membrane (HEM) was measured. All measurements were conducted at 32°C. Results The partition coefficient for glucose [mean ± SD (no. of samples)] was 0.65 ± 0.09 (n = 25) for dermis, 0.81 ± 0.06 (n = 10) for TSE, and 0.53 ± 0.12 (n = 9) for SC. Glucose diffusivity in dermis was calculated to be 2.64 ± 0.42 × 10⁻⁶ cm²/s (n = 14). Glucose diffusivities in the viable epidermis estimated from TSS permeation, TSE desorption, and HEM desorption were 0.075 ± 0.050 × 10⁻⁶ cm²/s (n = 5), 0.037 ± 0.018 × 10⁻⁶ cm²/s (n = 4), and 1.0 ± 0.6 × 10⁻⁶ cm²/s (n = 4), respectively. Conclusion The tissue/buffer partition coefficient of glucose in all skin layers was found to be less than unity, suggestive of excluded volumes in each layer. Glucose diffusivity in human dermis was found to be one third of its value in water, indicative of hindered diffusion related to the structural components of the tissue. A substantially lower value for glucose diffusivity in viable epidermis is suggested.     

Percutaneous absorption of parachlorometaxylenol

The in vitro percutaneous absorption of p-chlorometaxylenol (PCMX), a topical antiseptic, was investigated using pig skin. Solubility studies in aqueous Tween 80 solutions were performed to develop a surfactant solubilized formulation. In vitro diffusion studies were carried out using side-by-side diffusion cells and pig skin. The diffusion of PCMX through pig skin followed a steady-state flux model. The total permeation coefficient of PCMX through pig skin was found to be 2.97 × 10⁻⁴ ± 9.61 × 10⁻⁵ cm/min. It was observed that 18.1 ± 0.98% of the initial amount of PCMX was extracted from the skin.     

Analysis of in Vitro Skin Permeation of 22-Oxacalcitriol Having a Complicated Metabolic Pathway

Purpose The purpose of this study is to analyze simultaneous skin permeation and metabolism of 22-oxacalcitriol (OCT) having several metabolites in skin by observing skin permeation of only unchanged OCT through excised rat skin. Methods A diffusion model including metabolic processes was employed to express simultaneous skin permeation and metabolism of OCT. In vitro permeation experiments of OCT from Oxarol^? ointment through full-thickness and stripped rat skin were carried out using Franz-type diffusion cells. Time courses of unchanged OCT amounts in ointment, skin, and receptor fluid were determined and fitted to diffusion equations to obtain permeation parameters and a metabolic rate. Results Fitting curves of the skin permeation profile obtained by the model were sufficiently close to observed data of unchanged OCT amounts in ointment, skin, and receptor fluid. The following parameters were obtained: metabolic rate of 1.37 × 10⁻¹ h⁻¹, and diffusion constants of OCT in stratum corneum (SC) (D_SC) and viable epidermis and dermis (VED) (D_VED) of 1.50 × 10⁻⁷ and 2.96 × 10⁻⁴ cm²/h, respectively. The partition coefficient of OCT for SC/ointment (K_SC/D) was 7 times greater than that of VED/ointment (K_VED/D). Conclusions The present analysis made it possible to calculate skin permeation parameters (partitioning, diffusivity, and metabolic rate) of OCT without requiring metabolic information, e.g., quantification of metabolites or identification of metabolic pathways. This would be widely applicable for drugs that are not suitable for conventional methods due to complicated metabolic pathways.     

Novel carbopol-based transfersomal gel of 5-fluorouracil for skin cancer treatment: in vitro characterization and in vivo study

Abstract

5-fluorouracil (5-Fu) is an antineoplastic drug, topically used for the treatment of actinic keratosis and nonmelanoma skin cancer. It shows poor percutaneous permeation through the conventionally applicable creams and thus inefficient for the treatment of deep-seated skin cancer. In the present article, transfersomal gel containing 5-Fu was investigated for the treatment of skin cancer. Different formulation of tranfersomes was prepared using Tween-80 and Span-80 as edge activators. The vesicles were characterized for particle size, shape, entrapment efficiency, deformability and in vitro skin permeation. Optimized formulation was incorporated into 1% carbopol 940 gel and evaluated for efficacy in the treatment of skin cancer. 5-Fu-loaded transfersomes (TT-2) has the size of 266.9?±?2.04?nm with 69.2?±?0.98% entrapment efficiency and highest deformability index of 27.8?±?1.08. Formulation TT-2 showed maximum skin deposition (81.3%) and comparable transdermal flux of 21.46?µg/cm²?h. The TT-2-loaded gel showed better skin penetration and skin deposition of the drug than the marketed formulation. Composition of the transfersomal gel has been proved nonirritant to the skin. We concluded that the developed 5-Fu-loaded transfersomal gel improves the skin absorption of 5-Fu and provide a better treatment for skin cancer.     

Chemoprevention of skin cancer using low HLB surfactant nanoemulsion of 5-fluorouracil: a preliminary study

Abstract

Oral delivery of 5-fluorouracil (5-FU) is difficult due to its serious adverse effects and extremely low bioavailability. Therefore, the aim of present investigation was to develop and evaluate low HLB surfactant nanoemulsion of 5-FU for topical chemoprevention of skin cancer. Low HLB surfactant nanoemulsions were prepared by oil phase titration method. Thermodynamically stable nanoemulsions were characterized in terms of droplet size distribution, zeta potential, viscosity and refractive index. Selected formulations and control were subjected to in vitro skin permeation studies through rat skin using Franz diffusion cells. Optimized formulation F9 was subjected to stability and in vitro cytotoxic studies on melanoma cell lines. Enhancement ratio was found to be 22.33 in formulation F9 compared with control and other formulations. The values of steady state flux and permeability coefficient for formulation F9 were found to be 206.40?±?14.56?µg?cm^?2?h^?1 and 2.064?×?10^?2?±?0.050?×?10^?2?cm?h^?1, respectively. Optimized formulation F9 was found to be physical stable. In vitro cytotoxicity studies on SK-MEL-5 cancer cells indicated that 5-FU in optimized nanoemulsion is much more efficacious than free 5-FU. From these results, it can be concluded that the developed nanoemulsion might be a promising vehicle for chemoprevention of skin cancer.     

高剂量氨甲喋呤的临床药代动力学

本文研究了接受高剂量氨甲喋呤(MTX)结合甲酰四氢叶酸钙(CF)保护化疗的20例恶性肿瘤病人的药代动力学特性。用药剂量17～62mg/kg。静脉滴注MTX结束后血药浓度迅速下降,药—时曲线符合开放三室模型,用阻尼非线性最小二乘法计算的t1/2π0.26±0.09,t1/2α1.43±0.22,t1/2β8.24±2.36小时。据血药浓度公式,在给药后早期可以预测24小时以后的血浓度,可及早发现清除不良的病人。接受治疗的所有病人无严重毒性发生,24、48小时血浓度<5.4×10^-6M、6.21×10^-7M是安全的。     

Interactions between tetraethylammonium and methohexitone at the chick neuromuscular junction: Experiments with the moving fluid electrode technique

The effect of methohexitone on the depolarization and contracture responses produced by tetraethylammonium (TEA), acetylcholine (ACh) and repetitive indirect stimulation were investigated, using the moving fluid electrode technique, in the chick biventer cervicis (BVC) nerve muscle preparation. TEA (4.8 × 10^?4?4.8 × 10^?2 M) produced contracture and depolarization responses which were concn-dependent. These responses were potentiated by methohexitone (8.8 × 10^?5 M). The mean ED₅₀S for the contracture responses in the control Krebs solution and with methohexitone were (mean ± S.E.M.) 6.5 ± 0.03 × 10^?3 M and 1.3 ± 0.04 × 10^?3 M (N = 6) respectively. The mean ED₅₀S for the depolarizations were (mean ± S.E.M.) 5.9 ± 0.1 × 10^?3 and 1.5 ± 0.06 × 10^?3 M (N = 6) respectively. ACh (5.5 × 10^?6?1.1 × 10^?2 M) produced contracture and depolarization responses which were concn-dependent. These responses were reduced by methohexitone (8.8 × 10^?5 M). The mean ED₅₀S for the contracture responses in the control Krebs solution and with methohexitone were (mean ± S.E.M. 2.4 ± 0.21 × 10^?4 and 2.3 ± 0.1 × 10^?3 M (N = 6) respectively. The mean (± S.E.M.) ED₅₀S for the depolarizations were 8.4 ± 0.33 × 10^?4 and 3.7 ± 0.14 × 10^?3 M (N = 6), respectively. Repetitive indirect stimulation, at 1–20 Hz, produced contraction and depolarization responses which were frequency-dependent. These responses were slightly potentiated by methohexitone (8.8 × 10^?5 M). The mean (± S.E.M.) frequency₅₀S for the contractions produced in the control Krebs solution and with methohexitone were 9.2 ± 0.1 and 8.5 ± 0.2 Hz (N = 6) respectively. The mean frequency₅₀S for the depolarizations were (mean ± S.E.M.) 7.2 ± 0.1 and 5.8 ± 0.19 Hz (N = 6) respectively. It is concluded that TEA may have a direct post-synaptic action, in addition to releasing ACh from the presynaptic nerve terminals. TEA produces more contracture tension than does ACh for a given level of membrane depolarization. Methohexitone, non-competitively, reduces the responses produced by applied ACh whereas it potentiates those produced by TEA and repetitive nerve stimulation.     

The In Vitro Permeability Coefficient and Short-Term Absorption Rates for Vinyl Toluene Using Human Cadaver Skin Mounted in a Static Diffusion Cell Model

Vinyl toluene is one of several methylstyrene monomers that provide improved performance in resins for specialty paints, hydrocarbon resins for adhesives, specialty polymers, and unsaturated polyester resins. The purpose of this study was to determine a permeability coefficient (Kp) and short-term absorption rate for vinyl toluene using human cadaver skin mounted in an in vitro static diffusion cell model with an exposure area of 0.64 cm². For the Kp determination, vinyl toluene was applied at a rate of 100 μL/cm² to 6 skin replicates representing 4 human subjects. Serial receptor fluid samples were collected at 1, 2, 4, 8, 12, 24, 36, and 48 h postapplication and analyzed for vinyl toluene by HPLC-UV. Based on the slope at steady-state (203.3 μg cm^?2 h^?1 ± 120.0 μg cm^?2 h^?1) and the concentration of the applied dose of vinyl toluene, taken as its density (894,600 μg/cm³), the Kp was calculated to be 2.27 × 10^?4 cm/h (±1.34 × 10^?4 cm/h). For the short-term absorption experiments, 12 skin replicates representing 3 human subjects were employed. Following 10- and 60-min exposures to a finite dose of vinyl toluene (10 μL/cm²), the respective short-term absorption rates were calculated to be 66.0 (±29.9) and 104.2 (±63.0) μg cm^?2 h^?1. These data provide industrial hygienists and safety personnel values to estimate the amount of vinyl toluene that may be absorbed via the dermal exposure route, given a variety of exposure scenarios, and the time it takes (skin absorption time) to reach a body burden equal to the Occupational Safety and Health Administrative permissible exposure level (OSHA PEL) or ACGIH TLV.     

In Vitro Studies of Intestinal Permeability and Hepatic and Intestinal Metabolism of 8-Prenylnaringenin, a Potent Phytoestrogen from Hops (Humulus lupulus L.)

Purpose The absorption potential and metabolism of 8-prenylnaringenin (8-PN) from hops (Humulus lupulus L.) were investigated. 8-PN is a potent estrogen with the potential to be used for the relief of menopausal symptoms in women. Methods Monolayers of the human intestinal epithelial cancer cell line Caco-2 and human hepatocytes were incubated with 8-PN to model its intestinal absorption and hepatic metabolism, respectively. Results The apparent permeability coefficients for 8-PN in the apical-to-basolateral and basolateral-to-apical directions of a Caco-2 monolayer were 5.2 ± 0.7 × 10⁻⁵ and 4.9 ± 0.5 × 10⁻⁵ cm/s, respectively, indicating good intestinal absorption via passive diffusion. Both glucuronide and sulfate conjugates of 8-PN were detected in the Caco-2 cell incubations. The 4′-O-glucuronide was the predominant Caco-2 cell metabolite, followed by 7-O-sulfate and 4′-O-sulfate. Both phase I and phase II metabolites of 8-PN were formed by human hepatocytes. The 7-O-glucuronide was the most abundant hepatocyte metabolite, and no sulfate conjugates were detected. Incubations with various cDNA-expressed UDP-glucuronosyltransferases indicated that the isozymes UGT1A1, UGT1A6, UGT1A8, and UGT1A9 were responsible for glucuronidation of 8-PN. Conclusions Although orally administered 8-PN should be readily absorbed from the intestine, its bioavailability should be reduced significantly by intestinal and hepatic metabolism.     

吲哚美辛对5-氟尿嘧啶在大鼠体内药代动力学的影响

目的探讨吲哚美辛(Ind)增强5-氟尿嘧啶(5-Fu)的抗肿瘤作用是否与药代动力学的变化有关。方法采用反相高效液相色谱(HPLC)法测定大鼠血浆中5-Fu浓度,数据用“3p97”程序处理。结果单用和联用Ind后,5-Fu在大鼠体内的药代动力学均为一室模型,t1/2ka分别为(3.8±2.0)和(4.4±2.7)min,t1/2ke分别为(57±46)和(101±48)min,ke分别为(0.018±0.010)和(0.009±0.005)min-1,cmax分别为(7.0±1.8)和(19±8)mg.L-1,AUC分别为(0.7±0.5)和(3.5±2.4)g.min.L-1,Cl分别为(100±50)和(24±21)mg.kg-1.min-1。说明联用Ind后,5-Fu的作用时间延长,在大鼠体内的经时过程增长。结论Ind能延缓5-Fu在大鼠体内的消除,两者联用时应注意调整给药剂量和对5-Fu进行临床给药监测。