黄芪、灯盏花素复方制剂对阿尔茨海默病大鼠记忆能力及血、脑组织中超氧化物歧化酶、过氧化脂质和乳酸脱氢酶的影响

摘 要 目的：探讨黄芪、灯盏花素复方制剂（HDs）对阿尔茨海默病（AD）大鼠红细胞、脑组织中超氧化物歧化酶（SOD）、过氧化脂质丙二醛（MDA）以及乳酸脱氢酶（LDH）的影响。方法: 随机将50只大鼠分为正常对照组、脑复康阳性对照组（0.15 g·kg^-1·d^-1,灌胃）、模型组以及HDs低剂量（HDs1,1.5 ml·kg^-1·d^-1,腹腔注射）、HDs高剂量组（HDs 2,3.0 ml·kg^-1·d^-1,腹腔注射）,以三氯化铝（5 mg·kg^-1·d^-1,灌胃）和D 半乳糖（40 mg·kg^-1·d^-1,腹腔注射）建立AD大鼠动物模型。90 d后,测定各组大鼠的近期学习记忆能力,检测各组大鼠红细胞、脑组织SOD、MDA以及LDH水平。结果: 与AD模型组比较,HDs各剂量组大鼠学习记忆能力明显提高,红细胞及脑组织中SOD、LDH的活性明显升高,MDA含量明显降低,差异均有统计学意义(Ｐ<0.05或Ｐ<0.01);但尚未恢复至正常水平（Ｐ<0.05或Ｐ<0.01）。HDs2组部分指标明显优于脑复康阳性对照药组和HDs1组(Ｐ<0.05或Ｐ<0.01)。结论:黄芪、灯盏花素复方制剂对AD大鼠的学习记忆障碍有明显的改善,能有效提高AD大鼠红细胞及脑组织SOD、及LDH的活性,降低MDA的浓度。     

环孢素A联合中/低剂量泼尼松治疗进展性IgA肾病观察

摘 要 目的：探讨环孢素A联合中/低剂量泼尼松治疗进展性IgA肾病的临床疗效和安全性。方法：进展性IgA肾病患者120例随机分为观察组和对照组每组60例。对照组晨起顿服大剂量泼尼松,起始剂量1.0 mg·kg^-1·d^-1,最大量60 mg·d^-1,6周后（或尿蛋白转阴后2周）逐渐减量,至12周时减至0.5 mg·kg^-1·d^-1,维持治疗;观察组给予环孢素A+泼尼松治疗,环孢素A起始剂量100 mg·d^-1,根据血药浓度调整用量,最大不超过5.0 mg·kg^-1·d^-1, 使环孢素 A 谷浓度维持在100～200 mg·ml^-1;波尼松起始剂量0.5 mg·kg^-1·d^-1,最大量30 mg·d^-1。两组均治疗6个月以上。分别于治疗2,4,6,8,12,24周观察两组患者24 h 尿蛋白、血白蛋白、肌酐、尿酸等指标变化,评价两组的临床疗效和药品不良反应。结果：观察组治疗4,8,12,24周时的总缓解率均显著高于对照组（P<0.05）。治疗2,4,8,12,24周时,两组24 h 尿蛋白均显著下降（P<0.05）,且观察组明显低于对照组（P<0.05）。观察组治疗4,8,12,24周时血白蛋白较治疗前显著上升（P<0.05）,且显著高于对照组同期（P<0.05）;而对照组治疗期间血白蛋白无明显变化（P>0.05）。治疗前后两组患者血肌酐和尿酸水平比较,差异无统计学意义（P>0.05）。两组药品不良反应发生率比较,差异无统计学意义（P>0.05）。结论：环孢素A联合中/低剂量泼尼松治疗进展性IgA肾病临床疗效好,安全性高,值得临床推广。     

三七总皂苷肠溶微丸对高脂血症家兔血液流变学的影响

摘 要 目的：探讨三七总皂苷（PNS）肠溶微丸对家兔血液流变学的影响。方法: 建立空白对照组、模型组、血栓通注射剂（冻干）组（15 mg·kg^-1·d^-1,im）、PNS肠溶微丸高剂量组（45 mg·kg^-1·d^-1,ig）、中剂量组（30 mg·kg^-1·d^-1,ig）、低剂量组（15 mg·kg^-1·d^-1,ig）,予高脂饲料配方灌胃造模;运用血液流变学检测方法测定各组全血黏度、血浆黏度 、红细胞聚集指数、红细胞刚性指数、红细胞电泳率5项指标。结果: 模型组血液流变学5项指标明显高于空白对照组(P<0.01),提示动物模型复制成功。与模型组比较, PNS肠溶微丸高、中剂量组均能明显降低全血黏度和血浆黏度（P<0.01或P<0.05）;PNS肠溶微丸低剂量组能显著降低中切黏度及血浆黏度（P<0.05）;PNS肠溶微丸高、中、低剂量组红细胞聚集指数显著降低（P<0.01）;PNS肠溶微丸高、中剂量组红细胞刚性指数显著降低（P<0.01或P<0.05）;PNS肠溶微丸高、中、低剂量有降低红细胞电泳率的趋势,但差异无统计学意义（P>0.05）。PNS肠溶微丸中剂量组降低中切黏度效果优于血栓通注射剂（冻干）组（P<0.05）。结论:PNS肠溶微丸能降低家兔全血黏度、血浆黏度、红细胞聚集指数、红细胞刚性指数、红细胞电泳率等指标,发挥PNS肠溶微丸活血化瘀、抑制血栓形成、增加心脑血管的血液供应的作用。     

膜性肾病患者他克莫司血浓度与给药剂量的相关性研究

摘 要 目的： 研究他克莫司治疗膜性肾病的有效血药浓度与给药剂量的相关性。 方法: 41例膜性肾病患者给予他克莫司联合小剂量激素治疗,采用均相酶扩大免疫分析法测定他克莫司全血谷浓度,根据患者24h尿蛋白、血浆白蛋白及肾功能变化进行临床疗效评价,分析他克莫司治疗膜性肾病的疗效与血药浓度及给药剂量的相关性。结果:完全缓解组患者他克莫司血药浓度为（7.47±2.74）ng·ml^-1,给药剂量为（0.047±0.007）mg·kg^-1·d^-1;部分缓解组血药浓度为（5.72±1.19）ng·ml^-1,给药剂量为（0.049±0.008）mg·kg^-1·d^-1;无缓解组血药浓度为（3.30±1.08）ng·ml^-1,给药剂量为（0.052±0.01）mg·kg^-1·d^-1。结论: 他克莫司血药浓度在（5.10～9.32）ng·ml^-1时有较好治疗效果,部分患者血药浓度不随给药剂量的增加而提高。     

阿奇霉素与乙酰螺旋霉素交替使用治疗小儿支原体肺炎疗效观察

摘 要 目的： 比较阿奇霉素与乙酰螺旋霉素交替使用及阿奇霉素单用序贯治疗小儿支原体肺炎的疗效。方法: 门诊支原体肺炎患儿84例随机分成A组43例和B组41例。A组先用阿奇霉素（10mg·kg^-1·d^-1ivd qd）静滴7 d,停药4 d后继用阿奇霉素10 mg·kg^-1·d^-1 po qd序贯治疗（用3 d停4 d）,连用3周;B组先用阿奇霉素（10mg·kg^-1·d^-1ivd qd）静滴7 d,然后继用乙酰螺旋霉素25～30 mg·kg^-1·d^-1 po, tid,连用2周。对比两组的临床疗效和药品不良反应发生情况。结果: A组与B组总有效率分别为86.0%和100.0%,B组明显高于A组(P<0.05);两组不良反应发生率差异无统计学意义（P>0.05）。结论:阿奇霉素与乙酰螺旋霉素交替使用治疗小儿支原体肺炎优于阿奇霉素单用序贯治疗。     

玫瑰花对脂多糖诱导的大鼠乳腺炎的影响

摘 要 目的： 探讨玫瑰花总黄酮对脂多糖（LPS）诱导的大鼠乳腺炎的影响。方法: 脂多糖注射诱导大鼠乳腺炎,观察玫瑰花总黄酮（200,100 mg·kg^-1·d^-1）给药干预对乳腺组织切片形态学变化、乳腺氧化应激和炎症应激水平的影响。结果: 与对照组相比,LPS注射导致大鼠乳腺组织大量炎性细胞浸润, SOD和GPx的活力显著下降,同时MDA水平大幅上升,组织IL-1β、IL-6和TNF-α的水平均显著升高。与模型组比较,低剂量组和高剂量组均能显著改善模型动物乳腺的病理变化,恢复乳腺组织抗氧酶SOD和GPx的活力(P<0.05或P<0.01),降低了MDA的水平（P<0.01）,并抑制促炎细胞因子IL-1β、IL-6和TNF-α水平的上升(P<0.05或P<0.01)。结论:玫瑰花总黄酮有潜在的抗乳腺炎活性。     

石榴皮鞣质对大鼠肝药酶活性的影响

摘 要 目的：研究石榴皮鞣质对正常大鼠肝药酶活性的影响。方法: 将30只Wistar大鼠随机分为5组：空白对照组,石榴皮鞣质高、中、低剂量组,苯巴比妥钠阳性对照组。空白对照组给予生理盐水,石榴皮鞣质高、中、低剂量组分别按150,100,75 mg·kg^-1·d^-1连续灌胃给药7 d,苯巴比妥钠组给予苯巴比妥钠注射液,按80 mg·kg^-1·d^-1连续腹腔给药5 d。实验结束后采用UV法测定各组大鼠肝脏微粒体中Ⅰ相代谢酶和Ⅱ相代谢酶活性。结果: 与空白对照组相比,石榴皮鞣质高、中、低剂量组均能降低细胞色素P450（CYP450）总蛋白和细胞色素b5（CYPb5）含量及抑制氨基比林N-脱甲基酶（ADM）活性,差异有统计学意义（P<0.01）;石榴皮鞣质高、中剂量组能显著抑制红霉素N-脱甲基酶（ERD）活性,差异有统计学意义（P<0.01）;石榴皮鞣质高剂量组能显著降低谷胱甘肽S 转移酶（GST）活性,差异有统计学意义（P<0.01）。结论: 石榴皮鞣质对正常大鼠肝药酶活性具有一定抑制作用,能降低CYP3A 和 CYP2E1的表达,且与给药剂量有关。     

络塞维改善D-半乳糖致亚急性衰老大鼠的学习记忆力的机制初探

摘 要 目的： 观察络塞维改善D-半乳糖致亚急性衰老大鼠学习记忆力下降的作用,并初步研究其作用机制。方法: 将48只SD大鼠随机分为对照组,模型组,阳性药物组,络塞维6、12、24 mg·g^-1剂量组。除对照组外,所有大鼠颈部皮下注射 D-半乳糖120 mg·kg^-1·d^-1造模。在给药进行4周后,采用Morris水迷宫测试各试验组大鼠学习记忆能力差异,血气分析仪测定大鼠脑中血氧分压（PO₂）,血氧浓度（O₂）及血氧饱和度（SaO₂）,并在试验结束后处死大鼠测定脑组织中超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化酶（GSH Px）活性和丙二醛（MDA）含量。结果: 络塞维12、24 mg·g^-1·d^-1可显著缩短衰老大鼠在Morris水迷宫的潜伏期（P<0.01或P<0.05）,并减少大鼠的游泳总距离和错误角度。同时,给予络塞维6,12,24 mg·g^-1·d^-1治疗衰老大鼠均能不同程度提高大鼠脑内PO₂,  O₂和SaO₂浓度, SOD、CAT、GSH Px活性及降低MDA含量,并具一定量效关系。结论:络塞维可改善D 半乳糖所致大鼠学习记忆下降现象,该作用可能与回升血氧含量,并保护SOD、CAT、GSH Px等酶活性,降低MDA生成有关。     

中国人群不同剂量阿托伐他汀抗动脉粥样硬化致肝功能异常的系统评价

摘 要 目的:系统评价中国人群使用10mg·d^-1和80mg·d^-1阿托伐他汀抗动脉粥样硬化致肝功能异常的差异。方法：计算机检索PubMed、EMBASE、CENTRAL、ClinicalTrial、CBM、CNKI、VIP、万方等数据库（截止2014年12月）,纳入中国人群不同剂量阿托伐他汀抗动脉粥样硬化的随机对照试验。运用STATA软件和间接治疗比较（Indirect Treatment Comparisons,ITC）软件分别计算10 mg·d^-1与80 mg·d^-1相比引起肝功能异常的直接效应和间接效应,以相对危险度（RR）及95%可信区间（95%CI）表示。结果：共纳入27篇文献,病例数2 507例,治疗时间最长为5年。10 mg·d^-1与80 mg·d^-1直接比较的研究有2个,两剂量相比致肝功能异常的直接效应RR=0.44（95%CI：0.07~2.95）。10 mg·d^-1与20 mg·d^-1,20 mg·d^-1与80 mg·d^-1,10 mg·d^-1与40 mg·d^-1,40 mg·d^-1与80 mg·d^-1直接比较的研究为15,2,9和1个,分别以20 mg·d^-1和40 mg·d^-1为中间桥梁,ITC分析显示10 mg·d^-1与80 mg·d^-1相比引起肝功能异常的间接效应值RR为0.584（95%CI：0.034~9.987）和0.437（95%CI：0.008~22.811）。按治疗时间<6个月和≥6个月进行亚组分析也显示10 mg·d^-1与80 mg·d^-1引起肝功能异常的效应值差异无统计学意义（P＞0.05）。 结论：基于10 mg·d^-1与80 mg·d^-1相比的直接效应和间接效应结果,中国动脉粥样硬化患者服用10 mg·d^-1或80 mg·d^-1阿托伐他汀后在肝功能异常方面的差异无统计学意义。     

活犀角与犀角抗炎作用的比较研究

摘 要 目的：比较活犀角与犀角的抗炎作用有无显著差异,为活犀角替代犀角提供实验依据。 方法: 通过大鼠足跖肿胀法和小鼠棉球肉芽肿法、耳廓肿胀法、腹腔染料通透法研究活犀角和犀角的抗炎作用。 结果: 与模型对照组比较,活犀角的高（440 mg·kg^-1）、中（220 mg·kg^-1）剂量组和犀角3个剂量组各时间点的足跖肿胀度差异有统计学意义（P＜0.05或P＜0.01）;活犀角和犀角的高（700 mg·kg^-1）、中（350 mg·kg^-1）剂量组能显著降低小鼠棉球肉芽肿的重量（P＜0.05）;活犀角和犀角3个剂量组（700,350,175 mg·kg^-1）均能明显降低二甲苯引起的小鼠耳廓肿胀（P＜0.05或P＜0.01）;犀角中（350 mg·kg^-1）剂量组,活犀角高（700 mg·kg^-1）、中（350 mg·kg^-1）剂量组的腹腔清洗液中伊文思兰的吸光度值显著降低（P＜0.05或P＜0.01）。活犀角与犀角相同剂量组间抗炎作用比较无显著差异。 结论: 活犀角与犀角均具有一定抗炎作用,本研究为活犀角在抗炎作用方面作为犀角的替代品进行使用提供了实验依据。     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

Mechanisms of antiplatelet and antithrombotic activity of midazolam in in vitro and in vivo studies

Dopamine regulates various physiological functions in the central nervous system and the periphery. Dysfunction of the dopamine system is implicated in a wide variety of disorders and behaviors including schizophrenia, addiction, and attention-deficit hyperactivity disorder. Medications that modulate dopamine signaling have therapeutic efficacy on the treatment of these disorders. However, the causes of these disorders and the role of dopamine are still unclear. Studying the dopamine system in a model organism, such as Caenorhabditis elegans, allows the genetic analysis in a simple and well-described nervous system, which may provide new insight into the molecular mechanisms of dopamine signaling. In this review, we summarize recent findings on pharmacological and biochemical properties of the C. elegans dopamine receptors and their physiological role in the control of behavior.     

Penetration and action of edoxudine in vitro and in vivo

The penetration of 5-ethyl-2'-deoxyuridine (edoxudine, Aedurid) from gel base with and without the addition of urea and other adjuvant has been studied in an in vitro model using guinea pig skin. The formulation of 3% edoxudine gel with 5% urea showed the best results. In vivo experiments on hairless mice infected intracutaneously with herpes simplex virus type 1 also showed this formulation's good efficacy as compared to other formulations.     

Extraction and determination of prednisolone in drugs and excipients in ointments and creams and the uniformity of distribution in prednisolone ointment

For the purpose of measuring the contents of prednisolone in low concentrated ointments and creams an instruction was elaborated that includes several steps of extraction, in the resulting solution of which the assay of the steroid by Blue Tetrazolium reaction will be done. The procedure permits the determination of prednisolone in presence of most of usual ingredients of ointment bases except wool alcohols. Also no influence is given by some remedies combined with prednisolone for topical application except coal tar solution. The results confirm a correct reflection of the steroid contents declared respectively the recovery of the steroid added to various ointment bases. Introducing discussion to content uniformity concerning low concentrated ointments is made, and some deviations are shown.     

Simultaneous Determination of Sulfation and Glucuronidation of Flavones in FVB Mouse Intestine in Vitro and in Vivo

Glucuronidation and sulfation are the two major phase II metabolic pathways for flavones, natural compounds that hold great potential for improving human health. We investigated the positional preference for sulfation and glucuronidation of seven structurally similar flavones in vitro and in situ. An FVB mouse intestinal perfusion model was used in addition to three small intestine S9 fractions catalyzing sulfation only (Sult enzymes), glucuronidation only (Ugt enzymes) or both (Sult and Ugt enzymes). In both the single and co‐reaction S9 systems, flavones containing 7‐OH groups were conjugated only at 7‐OH despite the presence of other hydroxyl groups, and 7‐OH glucuronidation was faster than sulfation (P < 0.05). The sulfation rate was enhanced in the Sult‐Ugt co‐reaction system, while glucuronidation was usually unchanged by the presence of Sult. In the intestinal perfusate, sulfation patterns were the same in the small intestine and colon, and the excretion rate of 7‐O‐sulfate was the fastest or second fastest. The excretion of 7‐O‐glucuronidates was faster in small intestine (P < 0.05) than in colon. The S9‐mediated sulfation rates of the different flavones were significantly correlated with the excretion rates of the same flavones from perfused intestine. In conclusion, flavone glucuronidation and sulfation rates were sensitive to minor changes in molecular structure. In intestinal S9 fractions, both Ugts and Sults preferentially catalyzed reactions at 7‐OH. The sulfation rate was significantly enhanced by simultaneous glucuronidation, but glucuronidation was unaltered by sulfation. Sulfation rates in mouse S9 fractions correlated with sulfation rates in perfused intestine. Copyright © 2011 John Wiley & Sons, Ltd.     

Strain-dependency in motor activity and in concentration and turnover of catecholamines in synchronized rats

Circadian rhythm in motor activity was studied with an Animex motimeter in six strains of rats (ACI, BH, BS, DA, LEW, TNO) synchronized by a 12 hr light: 12 hr dark cycle. ANOVA revealed significant interstrain differences in motor activity as well as in the concentration and turnover of central noradrenaline and dopamine. Strain-dependent differences were also found with regard to tyrosine hydroxylase inhibition on motor activity. However, no significant interstrain correlations were found between endogenous concentration and/or turnover rates of the catecholamines and motor activity in normal and drug-treated rats.     

Pharmacokinetics and tolerability of artesunate and amodiaquine alone and in combination in healthy volunteers

Objectives  The WHO recommends artemisinin-based combination therapies for treatment of uncomplicated falciparum malaria. At least 15 African countries have adopted artesunate plus amodiaquine as treatment policy. As no pharmacokinetic data on this combination have been published to date, we investigated its pharmacokinetic interactions and tolerability in healthy volunteers in Africa. Methods  In a randomized, three-phase, cross-over study, amodiaquine (10 mg/kg) and artesunate (4 mg/kg) were given as single oral doses to 15 healthy volunteers. Artesunate was given to all volunteers on day 0. On day 7 they received either amodiaquine or amodiaquine plus artesunate and the alternative regimen on day 28. The pharmacokinetics of artesunate and amodiaquine and their main active metabolites dihydroartemisinin and desethylamodiaquine were compared following monotherapy and combination therapy using analysis of variance. Results  Thirteen volunteers completed the study, and pharmacokinetic parameters could be determined for twelve volunteers. When given in combination, the mean AUC was lower for dihydroartemisinin [ratio 67% (95% CI 51–88%); P = 0.008] and desethylamodiaquine [ratio 65% (95% CI 46–90%); P = 0.015] when compared with monotherapy. Adverse events of concern occurred in four volunteers (27%): grade 3 transaminitis (n = 1), neutropaenia (n = 2), and hypersensitivity (n = 1). Conclusion  The total drug exposure to both drugs was reduced significantly when they were given in combination. The clinical significance of these interactions is unclear and must be studied in malaria patients. The frequency and nature of adverse events among the healthy volunteers were of concern, and suggest laboratory monitoring would be needed in malaria patients treated with artesunate plus amodiaquine.     

A review of in vitro and in vivo models of oesophageal and gastric cancer

Importance of the field: Oesophageal and gastric cancers are leading causes of cancer-related mortality. In the era of targeted therapy and individualized treatment strategies, novel treatments for upper-gastrointestinal cancers are only just emerging compared to significant advances in other solid tumour types such as colorectal, breast and lung cancers. Clinical trials are investigating the value of established targeted agents for the treatment of oesophageal and gastric malignancies; however none are used in routine clinical practice.

Areas covered in this review: In this review we have looked at current in vitro and in vivo models of oesophageal and gastric cancers which may improve our understanding of the biology of these tumours and lead to the development of new preventative, diagnostic and therapeutic approaches.

What the reader will gain: We discuss the limitations of our current models and the challenges associated with research into these cancers.

Take home message: The lack of appropriate models for drug development in oesophageal and gastric cancers has hindered the progress of targeted therapy in this field.     

葛根芩连煎剂中小檗碱在犬体内药动学研究

目的:测定葛根芩连煎剂与黄连单煎剂犬血中小檗碱的含量,分析配伍后(全方)对小檗碱体内过程的影响。方法:采用高效液相色谱法,测定不同时间点犬血浆中小檗碱的含量,WinNonlin软件计算药动学参数。结果:葛根芩连煎剂及黄连单煎剂中小檗碱在犬体内药-时曲线均符合一室模型,主要药动学参数AUC(0-∞)(1·25±0·06)、(14·71±0·54)(μg·h)/ml,tmax(1·92±0·31)、(3·03±0·07)h,Cmax(0·17±0·01)、(1·79±0·03)μg/ml。结论:葛根芩连煎剂配伍后与单方比较小檗碱入血浓度及生物利用度都降低。     

Comparative in vivo and in vitro studies of phenytoin protein binding and in vitro lipolysis in plasma of pregnant and nonpregnant rats

This investigation was designed to determine the cause of the changes in drug protein binding that occur in rat plasma, particularly in plasma from pregnant animals, during in vitro drug-protein binding measurements. In vivo estimates of phenytoin binding in plasma were obtained from steady-state CSF-plasma concentration ratios in pregnant and nonpregnant rats. Immediate ultrafiltration of heparin- or EDTA-anticoagulated plasma yielded phenytoin free fraction values that were in good agreement with in vivo estimates for nonpregnant rats but that were about one-third higher than in vivo estimates for pregnant animals. In vitro free fraction values tended to increase during incubation of plasma and/or during equilibrium dialysis. The concentrations of the four major endogenous free fatty acids were similar in plasma of pregnant and nonpregnant rats if determined immediately after blood collection. Six hours of incubation at 37 degrees C caused fatty acid concentrations to increase about fivefold and twofold in heparin-anticoagulated plasma from pregnant and nonpregnant animals, respectively. The corresponding increases in EDTA-anticoagulated plasma were only about twofold and 1.14-fold, respectively. These changes were associated with decreased plasma protein binding of phenytoin. The in vivo differences between pregnant and nonpregnant rats with respect to phenytoin binding in plasma are not due to differences in fatty acid concentrations, but the in vitro differences are due primarily to corresponding differences in free fatty acid concentrations if extensive in vitro lipolysis occurs.