盐酸氟桂利嗪辅助治疗癫痫临床观察

目的 研究盐酸氟桂利嗪辅助治疗癫痫疗效。方法 １９２例癫痫患者在卡马西平或丙戊酸钠治疗至少３月后,添加盐酸氟桂利嗪活治疗,口服盐酸氟桂利嗪５ｍｇ,每晚１次,共３月。结果 添加盐酸氟桂利嗪治疗后,发作次数明显减少（Ｐ〈０．０１）。总有效率４７．３％,丙戊酸钠组有效率５９．８％,卡马西平组有效率３７．１％。丙戊酸钠组明显优于卡马西平组（Ｐ〈０．０１）。结论 盐酸氟桂利嗪辅助治疗癫痫有效,与丙戊酸钠联用     

双丙戊酸钠与托吡酯预防偏头痛发作的疗效比较

目的研究比较双丙戊酸钠与托吡酯预防偏头痛发作的疗效及安全性。方法128例偏头痛患者随机分为双丙戊酸钠组（68例）与托吡酯组（60例）。其中,双丙戊酸钠组初始剂量为125mg／d,每5d后剂量增加125mg／d,直至剂量为750mg／d后维持该剂量;托吡酯组初始剂量为50mg／d,每5天后剂量增加50mg／d,直至剂量为150mg／d后维持该剂量;两组服药持续5个月;观察两组患者治疗前后的头痛发作频率、头痛程度和持续时间。结果持续服药5个月后：与治疗前相比,双丙戊酸钠与托吡酯均能有效降低偏头痛患者发作频率、头痛程度和持续时间;与托吡酯组相比,双丙戊酸钠组偏头痛患者的头痛发作频率、头痛强度与持续时间都显著性降低,差异均有统计学意义（P〈0．05）;且双丙戊酸钠的副作用更小（P〈0．05）。结论双丙戊酸钠与托吡酯组对偏头痛发作均有较好的预防作用,但双丙戊酸钠应用效果更好、更安全,值得推广使用。     

氟桂利嗪联合正天丸治疗偏头痛的疗效分析

目的：观察氟桂利嗪与正天丸合用治疗偏头痛的临床疗效。方法：将86例偏头痛患者随机分为对照组和观察组,各43例,对照组单用氟桂利嗪治疗,观察组联合应用氟桂利嗪与正天丸治疗,比较两组临床疗效。结果：与本组治疗前比较,两组患者疼痛程度、疼痛持续的时间和发作次数均有明显改善（P＜0.01）,但观察组改善较对照组更为显著（P＜0.01）;观察组治愈率为41.9%,总有效率为93.1%,均分别高于对照组的16.3%、76.8%（P＜0.05或P＜0.01）。结论：氟桂利嗪与正天丸合用治疗偏头痛较单用氟桂利嗪的疗效显著,值得临床推广。     

氟桂利嗪合并小剂量阿司匹林治疗偏头痛

目的：观察氟桂利嗪合并小剂量阿司匹林治疗偏头痛的疗效。方法：偏头痛病人１００例随机分为２组，治疗组５０例（男性９例，女性４１例；年龄３３±ｓ７ａ）用氟桂利嗪５ｍｇ，ｐｏ，ｑｄ，阿司匹林０．１５ｇ，ｐｏ，ｑｄ；对照组５０例（男性８例，女性４２例；年龄３３±７ａ）用氟桂利嗪１０ｍｇ，ｐｏ，ｑｄ。２组治疗均为８ｗｋ，并随访６ｍｏ。结果：治疗组总有效率为９０％，对照组为７２％，２组疗效差异显著（Ｐ＜０．０５）。副作用发生率分别为８％和１６％（Ｐ＞０．０５）。结论：氟桂利嗪合并小剂量阿司匹林对偏头痛有较明显的治疗作用，且能预防复发。     

复方天麻蜜环糖肽联合氟桂利嗪治疗月经期偏头痛

目的 观察复方天麻蜜环糖肽联合氟桂利嗪治疗月经期偏头痛的临床疗效并探讨其治疗机制。方法 月经期偏头痛患者120例随机分为治疗组和对照组。治疗组60例，予复方天麻蜜环糖肽片1．0g，每日3次，氟桂利嗪5mg，睡前服用；对照组60例，氟桂利嗪剂量及用法同治疗组一样。治疗3个月后根据患者治疗前后头痛发作次数、程度及持续时间的变化进行评定。结果 治疗组有效率为91．67％，对照组有效率为75．00％，两组间差异有统计学意义（P〈0．05）。结论 复方天麻蜜环糖肽片治疗月经期偏头痛疗效确切，与氟桂利嗪合用可明显提高临床疗效。     

盐酸氟桂利嗪与对乙酰氨基酚合用治疗偏头痛临床分析

目的探讨盐酸氟桂利嗪胶囊与对乙酰氨基酚合用治疗偏头痛的治疗效果。方法采用对照研究方法,将40例偏头痛患者给予每晚睡前口服盐酸氟桂利嗪胶囊（西比灵）10mg,加用对乙酰氨基酚片250mg,3次／d,10d为1个疗程作为治疗观察组;与同期38例偏头痛患者单纯每晚睡前口服盐酸氟桂利嗪胶囊（西比灵）10mg为对照组进行比较、分析。结果治疗观察组的有效率为92．50％,而对照组的总有效率只有68．42％。结论盐酸氟桂利嗪与对乙酰氨基酚合用治疗偏头痛疗效显著。     

甘露醇与氟桂利嗪治疗偏头痛的疗效比较

目的：甘露醇与氟桂利嗪治疗偏头痛近期疗效比较。方法：偏头痛病人４７例，随机分为２组。甘露醇组２４例（男性６例，女性１８例，年龄４０±ｓ８ａ）。用２０％甘露醇２５０ｍＬ静脉滴注，４０ｍｉｎ滴完，ｑｄ，连用３～５ｄ。氟桂利嗪组２３例（男性７例，女性１６例，年龄３９±８ａ）。用氟桂利嗪胶囊２粒（５ｍｇ／粒），ｐｏ，ｑｄ，用药３～５ｄ。结果：２组总有效率均为９６％（Ｐ＞０．０５）。２组用药后起效时间，甘露醇组是０．８±０．６ｄ，氟桂利嗪组是１．５±０．８ｄ，Ｐ＜０．０１。结论：２药治疗偏头痛的疗效近似，但甘露醇起效时间较氟桂利嗪迅速。     

氟桂利嗪预防偏头痛两种用法疗效对比研究

目的比较氟桂利嗪两种用法预防偏头痛发作的疗效,以期探寻偏头痛治疗的新策略。方法 62例偏头痛患者随机分为治疗1组和治疗2组,每组31例。治疗1组氟桂利嗪5mg/d,7天/周;治疗2组氟桂利嗪5mg/d,5天/周,周末不服药。第12周末观察两组头痛发作程度和临床疗效以及不良反应情况。结果两组头痛发作程度与治疗前比较均有下降（P〈0.05）,两组比较无统计学意义（P〉0.05）。且治疗2组不良反应发生率低。结论在不减低氟桂利嗪疗效的情况下,采取周末停药是预防偏头痛、减少不良反应的有效方法 。     

盐酸氟西汀联合盐酸氟桂利嗪治疗偏头痛37例疗效观察

目的观察盐酸氟西汀联合盐酸氟桂利嗪治疗偏头痛的疗效观察。方法将各型偏头痛患者73例随机分为2组,治疗组37例,应用盐酸氟西汀（百忧解）联合盐酸氟桂利嗪（西比灵）治疗。对照组36例,应用盐酸氟桂利嗪治疗。治疗6周以观察疗效。结果治疗组总有效率为89.2%明显高于对照组的69.4%,差异有统计学意义（P〈0.05）。结论盐酸氟西汀联合盐酸氟桂利嗪治疗偏头痛优于单用盐酸氟桂利嗪治疗,无明显不良反应。     

氟桂利嗪单用及联用血塞通治疗血管性偏头痛的临床随机对照研究

目的探讨及分析氟桂利嗪与血塞通联合用药对血管性偏头痛患者的临床效果。方法将我院近年的104例血管性偏头痛患者,随机分为对照组和治疗组,对照组患者按照说明书用法仅服用氟桂利嗪,治疗组在服用氟桂利嗪的基础上,增加血塞通,观察两组患者的临床疗效。结果在服用盐酸氟桂利嗪和血塞通一个疗程后,治疗组疼痛发作时间为（5．13±0．31）min,显著短于对照组（7．35±1．11）min,比较差异具有统计学意义（P〈0．05）;治疗组治疗有效率96．15％显著高于对照组86．53％,差异具有统计学意义（P〈0．05）。结论氟桂利嗪和血塞通联合用药对血管性偏头痛有良好的治愈及改善意义,值得临床广泛推广。     

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     

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.     

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.     

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.     

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.     

Mathematical modelling of in situ and in vitro efflux of ciprofloxacin and grepafloxacin

The efflux process due to p-glycoprotein-like mechanisms of ciprofloxacin (CIP) and grepafloxacin (GRX) has been studied "in situ" in rats and "in vitro" in Caco-2 cells. The results were modelled by a curve fitting procedure which allowed the characterization of the passive (Pd) and carrier mediated parameters (Vm and Km) from the raw data without initial velocities estimation. CIP absorption in rat was characterized as a passive diffusion at the assayed concentrations. Although the involvement of an efflux transporter cannot be ruled out, its relevance in the transport of the fluoroquinolone is negligible. In GRX absorption, an efflux process is implicated and it is detected in both absorption models. GRX permeability depends on the intestinal segment, reflecting the previously reported different expression level of the efflux transporters along the gut in rat. A first attempt to correlate the "in vitro" and the "in situ" data has been done. The mathematical model has been constructed using very simplistic assumptions and it will require further refinement but, nevertheless, the results are promising and demonstrate that a good modelling approach helps to identify the system critical parameters and how the system behaviour change when the parameters are modified as it happens when we move from the "in vitro" to the "in situ" level. Predicted versus experimental permeability values show a good correlation, demonstrating that the relevance of the secretion process "in situ" in rat can be predicted from the "in vitro" cell results.     

Comparison of in vitro and in vivo developmental toxicity and pharmacokinetics of phenytoin in the rat

The rat whole embryo culture was compared to an in vivo experiment with regard to embryotoxicity as well as exposure characteristics, using phenytoin as a model compound. Intra-embryonic concentrations and their embryotoxic effects were determined on gestation day 11 after in vitro administration of 50-150 microg/ml or in vivo gavage of 500-1500 mg/kg body-weight on gestation day 10. In addition, exposure kinetics were studied in vivo after a single oral dose on gestation day 10, and developmental defects on gestation day 21 were scored. The embryotoxic effects observed on gestation day 11 were more pronounced after in vitro exposure in comparison to in vivo exposure at similar intra-embryonic concentrations. Exposure of phenytoin on gestation day 10 in vitro via the culture medium resulted in general embryotoxicity on gestation day 11, whereas in vivo effects as determined on gestation day 11 were minimal. Plasma concentrations of phenytoin increased and plateaued around 35 microg/ml during the 48 hr monitoring period. Plasma concentration curves and pharmacokinetic parameters did not show remarkable differences between the dose groups, indicating that absorption is the limiting factor at the dose range used. Although the developmental effects were minimal as observed in vivo on gestation day 11, specific malformations (defects encompassing the urogenital. craniofacial and skeletal systems) were observed on gestation day 21. These findings show that with similar intra-embryonic concentrations of phenytoin the embryotoxicity in rat whole embryo culture was not comparable with the in vivo embryotoxicity as determined on gestation day 11. This discrepancy may at least partly be explained by differences in exposure characteristics.     

Comparison of pulmonary and hepatic glucuronidation and sulphation of ethanol in rat and rabbit in vitro

1. Pulmonary and hepatic UDP-glucuronyltransferase and sulphotransferase activities in subcellular fractions from rats and rabbits were determined, comparing ethanol with known substrates for these enzymes.

2. No ethyl glucuronide formation was detected with either hepatic or pulmonary microsomal incubations.

3. Chromatographic, autoradiographic and scintillation counting analysis indicated that ethanol is sulphated by rat and rabbit pulmonary cytosol, although this activity was approx. 2–6% of that in liver.

4. Rat hepatic and pulmonary sulphotransferase activities with β-naphthol were approx. 13 and 60 times higher than with ethanol, respectively.

5. Rabbit hepatic and pulmonary sulphotransferase activities with both substrates were higher than those in rat.