控释吲(口朶)美辛栓剂的溶出度和正常人药代动力学研究

本文研究了控释吲哚美辛栓剂(CRIS)的体外溶出速率,应用改进的荧光分光光度法测定了健康成人给药后的血药浓度,并经计算机处理得各药代动力学参数。CRIS的体外溶出属零级动力学过程,K_r^o=11.37%/h(t≤8 h)。体内试验表明CRIS达到了一定的控释效果,给药后血药水平较为稳定,持续时间长,体内0～8h的吸收速度亦符合表观零级动力学过程,K_α^o=9.60%/h。CRIS的体内外数据具有显著的相关性(r=0.9979,p<0.001)。     

Circadian changes in the absorption and elimination of theophylline in patients with bronchial obstruction

Summary Circadian variation in the serum concentration of theophylline has been reported in most patients receiving slow release oral preparations. To examine further the mechanism and clinical relevance of this change, an investigation has been made into the diurnal fluctuation in elimination kinetics during i.v. administration of theophylline and its serum concentration profile on oral treatment with a slow release preparation, in 8 hospitalized patients receiving it for bronchial obstruction. After reaching steady-state on a constant intravenous infusion, the total body clearance of theophylline (CL) was determined every 4–6 h from the steady-state concentration and the infusion rate. No systematic trend indicative of circadian changes in elimination kinetics was observed. The intraindividual fluctuation in CL during the observation period was small (coefficient of variation 4–11%). In contrast, on oral dosing a smaller area under the serum concentration-time curve was found during the night time (22.00–06.00). The results show that the circadian variation described in serum theophylline concentrations is due to delayed absorption at night. The elimination kinetics of theopyhlline do not change.     

The Beagle Dog as an Animal Model for a Bioavailability Study of Controlled-Release Theophylline Under the Influence of Food

Beagle dogs were evaluated as an animal model to study the effect of food on the bioavailability of two commercially available oral controlled-release theophylline products. The products were administered with and without food in single doses, and the bioavailability parameters were compared with those following an i.v. aminophylline dose. The total plasma theophylline clearance in dogs following an i.v. dose was 0.128 liter/hr/kg and the volume of distribution was 0.8 liter/kg using a one-compartment model. The absolute bioavailabilities of these two products under fasting conditions were 31 and 48%, respectively. The food increased the bioavailability of one product and decreased the bioavailability of the other. The overall trends in relative bioavailability of these two products with and without food appeared to be similar to those reported in humans.     

Dorsal horn opiate administration attenuates the perceived intensity of noxious heat stimulation in behaving monkey

In monkeys trained to detect and discriminate noxious heat stimuli, morphine microinjected into the medullary dorsal horn attenuated the perceived intensity of noxious heat in a dose- and stimulus-dependent fashion. These data demonstrate a pharmacologically specific effect of opiates on the sensory intensity component of pain at the earliest central relay pathway transmitting noxious information.     

A theophylline dosage regimen which reduces round-the-clock variations in plasma concentrations resulting from diurnal pharmacokinetic variation

Summary Slower drug absorption at night can leave residual drug from an evening dose of a sustained-release product remaining to be absorbed at the time of the next morning's dose, thereby giving higher plasma concentrations of the drug during the day than the night.When a capsule product releasing theophylline over 12 h after a morning dose was given repetitively at 8 a.m. and 8 p.m. for 4 days, daytime plasma concentrations from 4 h to 8 h after the dose were about 40% greater than corresponding night-time concentrations, and the mean steady-state concentration during the night-time interval was only 81% of that during the daytime interval.Altering the regimen to one capsule at 12 noon and one at 10 p.m. eliminated all significant differences between a.m. and corresponding p.m. plasma concentrations of theophylline and between the mean steady-state concentrations for each of the interdose intervals within a day.     

脑室注射生长抑素对大鼠痛阈和脑内单胺类递质的影响

报告脑室注射（icv)生长抑素（SST）对大鼠痛阈和脑内单胺类递质的影响。采用Wistar大鼠作实验和病理观察。结果：Icu SST5μg或IOμg可使大鼠痛阈升高，高效液相谱－电化学检测显示海马，下丘脑和脑干内5－HT和5－HIAA（5μg组脑干的隐外）含量显著增多；而三脑区内NE含量的变化却不一致。icv SST 20μg时，高效液相色谱－紫外检测显示海马，下丘脑的次黄嘌呤和黄嘌呤明显下降，但是脑组织出现水肿。icv SST 40μ g时，可见脑神经细胞核固缩等坏死性病理变化。提示有较严重毒性反应，临床用量不宜过大。     

苯妥英钠缓释片溶出度的研究

本文研究了苯妥英钠缓释片的处方、制备工艺。溶出度达到USP ⅩⅪ版苯妥英钠缓释胶囊在水中的溶出要求。即在30min溶出标示量的15～35%,60min溶出标示量的30～70%,120min溶出不低于标示量的75%。在2h内溶出曲线呈现一级线性关系。     

An in vitro study of the role of dentine in moderating the cytotoxicity of zinc oxide eugenol cement

The protective role of different dentine fractions and of dentine slices in moderating the cytotoxicity of zinc oxide eugenol (ZOE) was investigated. The collagen fraction of dentine powder provided increased protection over intact powder. Slices of dentine offered greater protection probably by providing a physical barrier to the diffusion of eugenol which may also bind to the contents of the dentine tubules. With increasing thickness of the dentine slices this protection was increased. ZOE stimulated calcium release from dentine but in view of the low levels attained it is unlikely that this process has any significant effect on the protective role of dentine.     

Quantal components of the synaptic potential induced in hippocampal neurons by activation of granule cells, and the effect of 2-amino-4-phosphonobutyric acid.

The probabilistic nature of excitatory postsynaptic potentials (EPSPs) induced monosynaptically in CA3 neurons by impulses of granule cells was studied in thin transverse sections of the guinea pig hippocampus. More than 600 EPSPs were recorded under several conditions, their amplitudes were measured, and histograms representing the EPSP amplitude distribution were constructed. Quantal parameters were estimated by the method of maximum likelihood. Of 9 neurons examined in the control solution, one neuron showed an exceptionally large number of transmission failures. The amplitude distribution of EPSPs recorded from this neuron could be described by Pascal statistics, but not by binomial or Poisson statistics. The EPSP amplitude distribution from the other neurons could be described by either binomial, Poisson, or Pascal predictions with a minor preference for the last statistic. When an apparently homogeneous group of data was divided into two subgroups and parameters were estimated separately, inconsistent values were obtained in some neurons with no failures. 2-Amino-4-phosphonobutyric acid (APB) suppressed the EPSPs reversibly at relatively low concentrations. Theoretical curves calculated according to the Pascal statistics fit quite well to the entire amplitude distribution of EPSPs recorded under the action of APB. The suppression of EPSPs by APB was accompanied by a marked decrease in mean quantal content (m) with no significant reduction in mean quantal amplitude (q). A quantum induced an increase in membrane conductance of about 150 pS. These results suggest that the release probability of the mossy fiber terminal fluctuates temporally according to a gamma distribution, and that APB reduces the liberation of the transmitter from mossy fiber terminals, thereby suppressing transmission between mossy fibers and CA3 neurons.     

Enhancement of monocyte chemotactic activity in the sera of psoriatic patients after heat treatment

The chemotactic activity for neutrophils and monocytes was examined in the sera of psoriatic patients and healthy controls using a Boyden chamber method. There were no significant differences in neutrophil chemotactic activity between the sera of psoriatic patients and healthy controls. However, the monocyte chemotactic activity of psoriatic serum was lower than that of control serum. Furthermore, there was a significant increase in the monocyte chemotactic activity of psoriatic sera after heat treatment (42°C, 1 hr). These results suggest that psoriatic serum has a defect of monocyte chemotaxis which can be corrected, in part, by heat treatment.