Dextromethorphan Pretreatment Induces Antipyrine Clearance in the Rat

Numerous agents that undergo extensive first-pass metabolism have been shown to inhibit oxidative drug metabolism. To examine whether this effect is related to the chemical structure or pharmacokinetic characteristics of the inhibiting agent, we determined the effect of dextromethorphan (a compound which exhibits pharmacokinetic similarities to, but is chemically dissimilar from, previously studied agents) on the disposition of antipyrine. A single oral dose of dextromethorphan hydrobromide, 100 mg/kg, 1 hr prior to antipyrine administration had no significant effect on the pharmacokinetics of this model substrate. The administration of dextromethorphan at the same dose twice daily for 3 days and an additional dose 1 hr prior to antipyrine administration resulted in a 33% increase in the clearance of antipyrine. These data indicate that dextromethorphan is capable of inducing hepatic microsomal enzymes. Studies are needed to determine if this effect also occurs upon chronic administration in humans. These data suggest that the pharmacokinetic characteristic of extensive first-pass metabolism is not necessarily associated with inhibition of drug metabolism.     

撒痛风注射液的反相HPLC测定法

以含氢氧化四乙基铵(TEA)的甲醇-水(42∶58)体系为流动相,以氨基比林为内标物,采用反相HPLC法用ODS柱对含有水杨酸钠、安替比林和咖啡因的复合制剂撒痛风注射液的含量进行测定,回收率分别为99.93±1.01％,99.91±0.70％,100.03±1.32％。15min即能完成分析,结果准确。     

Time-Dependent Disposition of β-Naphthoflavone in the Rat

The pharmacokinetics of -naphthoflavone (BNF) have been investigated in rats following various modes of intravenous administration. From intravenous bolus studies it was established that BNF showed a high blood clearance (130 ml/min/kg) and no detectable excretion of unchanged compound in the urine. The volume of distribution for BNF was large (6 L/kg), and binding to plasma proteins extensive (96%). Intravenous infusion studies where the length of infusion was increased from 1 to 8 hr showed marked signs of time-dependent pharmacokinetics. During continuous infusions the plasma concentrations accrued for approximately 1 hr, after which plasma concentrations declined in an apparent exponential fashion to a plateau value. In the short infusion studies the postinfusion half-life (27 min) was significantly shorter than the terminal half-life after bolus administration (40 min). Time-dependent clearance of BNF resulting from enhancement/induction of P450IA enzymes is proposed as the mechanism for these unusual pharmacokinetic features. The use of antipyrine as an independent probe for P450 activity gave similar trends in antipyrine clearance for various modes of BNF administration. Computer simulations based on an autoinduction model for time-dependent clearance were consistent with the observations on BNF in the rat.     

HPLC法测定复方氨林巴比妥注射液中氨基比林和安替比林的含量

目的:建立测定复方氨林巴比妥注射液中氨基比林和安替比林含量的方法。方法:采用Phenomenex C18色谱柱(250 mm×4.6 mm,5μm),以甲醇-水(45∶55)为流动相,检测波长285 nm,流速0.8 ml/min,柱温40℃。结果:氨基比林的线性范围为0.125~0.437 mg/ml(r=0.999 9),平均回收率为99.0%(n=6),安替比林的线性范围为0.050~0.176 mg/ml(r=0.999 9),平均回收率为101.1%(n=6)。结论:本方法简便快速,结果准确,重现性好,适用于复方氨林巴比妥注射液的含量测定。     

Effects of anesthesia on functional activation of cerebral blood flow and metabolism

Functional brain mapping based on changes in local cerebral blood flow (lCBF) or glucose utilization (lCMR(glc)) induced by functional activation is generally carried out in animals under anesthesia, usually alpha-chloralose because of its lesser effects on cardiovascular, respiratory, and reflex functions. Results of studies on the role of nitric oxide (NO) in the mechanism of functional activation of lCBF have differed in unanesthetized and anesthetized animals. NO synthase inhibition markedly attenuates or eliminates the lCBF responses in anesthetized animals but not in unanesthetized animals. The present study examines in conscious rats and rats anesthetized with alpha-chloralose the effects of vibrissal stimulation on lCMR(glc) and lCBF in the whisker-to-barrel cortex pathway and on the effects of NO synthase inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) on the magnitude of the responses. Anesthesia markedly reduced the lCBF and lCMR(glc) responses in the ventral posteromedial thalamic nucleus and barrel cortex but not in the spinal and principal trigeminal nuclei. L-NAME did not alter the lCBF responses in any of the structures of the pathway in the unanesthetized rats and also not in the trigeminal nuclei of the anesthetized rats. In the thalamus and sensory cortex of the anesthetized rats, where the lCBF responses to stimulation had already been drastically diminished by the anesthesia, L-NAME treatment resulted in loss of statistically significant activation of lCBF by vibrissal stimulation. These results indicate that NO does not mediate functional activation of lCBF under physiological conditions.     

依达拉奉对原代培养大鼠海马神经元放射性损伤的保护作用

目的:研究依迭拉奉对原代培养大鼠海马神经元放射性损伤的保护作用.方法:30 Gy的X射线单次照射培养至12 d的海马神经元,用DAPI染核方法检测海马神经元凋亡情况,用MDA含量及SOD活性试剂盒测定细胞培养液MDA含量及SOD活性.结果:各组之间核固缩分数差异有统计学意义(P＜0.01),30 Gy组在照射后24 h核固缩百分数为(25.2±4.02)%,较0 Gy组差异有统计学意义,P＜0.01;30 Gy+依达拉奉100 mol/L组在照射后24 h核固缩百分数为(7.68±2.31)%,较30 Gy组及0 Gy组差异均有统计学意义(P＜0.01).各组之间MDA含量及SOD活性差异有统计学意义(P＜0.01).结论:依达拉奉通过降低自由基水平而对放射损伤的大鼠海马神经元起到保护作用.     

米格来宁片有关物质和含量测定方法研究

目的：建立米格来宁片有关物质与含量测定的HPLC方法。方法：采用Thermo Acclaim TM 120 C18柱（4.6mm×250mm，5μm）色谱柱；有关物质流动相：以0.01mol/L醋酸钠溶液-乙腈进行梯度洗脱；含量测定流动相为0.01mol/L醋酸钠溶液-乙腈（85:15）；流速1.0mL·min-1；检测波长275nm；进样量10μL。结果：安替比林和咖啡因分别与11种杂质完全分离，分离度大于1.5，测定杂质F校正因子为1.01，采用高分辨液质联用仪和ADMET Predictor软件推断主要未知杂质结构与毒性；含量测定咖啡因在11.0~109.6μg/mL浓度范围内线性关系良好（r=1.0000），平均回收率为99.03%（n=9），定量限为4.4ng；安替比林在109.96~1099.6μg/mL浓度范围内线性关系良好（r=1.0000），平均回收率为100.56%（n=9），定量限为11.0ng。结论：本方法专属、灵敏、简便，可用于测定米格来宁片中有关物质（杂质F≤0.03%，总杂质≤0.05%）以及安替比林和咖啡因的含量(安替比林：98.8%~101.4%，咖啡因：84.4%~107.5%)。