Pharmacologic evaluation of loratadine (SCH 29851), chlorpheniramine and placebo

Summary The antihistaminic effect of loratadine (160 mg) was compared in twenty-four normal male volunteers to chlorpheniramine maleate (4 mg) and placebo in a double blinded 3-way cross-over study of latin square design. After receiving single oral doses of each medication, the wheal response to serial 0.1 ml intradermal histamine (2 µg) and saline (control) injections were recorded over a 24-h period. The calculated wheal areas were compared to baseline measurements. The results were analyzed by analysis of variance. Loratadine exhibited a more pronounced inhibition of histamine wheal formation than placebo or chlorpheniramine maleate (p<0.003). In contrast to chlorpheniramine maleate which had a duration of action of only 3 h, loratadine inhibited the response for the entire observation period between 1 and 24 h post-dose. Although sedation was observed less frequently with loratadine (Placebo,n=2; chlorpheniramine,n=3; and loratadine,n=1), the relative incidence were not statistically significant.     

Influence of Plasticizer Level on the Drug Release from Sustained Release Film Coated and Hot-Melt Extruded Dosage Forms

In the current study, the influence of plasticizer level on drug release was investigated for solid dosage forms prepared by hot-melt extrusion and film coating. The properties of two highly water-soluble compounds, diltiazem hydrochloride (DTZ) and chlorpheniramine maleate (CPM), and a poorly water-soluble drug, indomethacin (IDM), were investigated in the melt extrudates containing either Eudragit® RSPO or Eudragit® RD 100 and triethyl citrate (TEC) as the plasticizer. In addition, pellets containing DTZ were film coated with Eudragit® RS 30D and varying levels of TEC using a fluidized bed coating unit. Differential scanning calorimetry (DSC) demonstrated that both CPM and IDM exhibited a plasticization effect on the acrylic polymers, whereas no plasticizing effect by DTZ on Eudragit® RSPO was observed. Thermogravimetric analysis (TGA) was used to investigate the thermal stability of the DTZ, Eudragit® RSPO and TEC at 140 °C, the maximum temperature used in the hot-melt extrusion process. The chemical stability of DTZ and IDM in the extrudate following hot-melt processing was determined by high pressure liquid chromatography (HPLC). Drug release rates of both DTZ and CPM from hot-melt extrudates increased with an increase in the TEC level in the formulations, while the release rate of DTZ from the Eudragit® RS 30D–coated pellets decreased with an increase in TEC in the coating dispersion. This phenomenon was due to the formation of a reservoir polymeric structure as a result of the thermal stress and shear stress involved in the hot-melt extrusion process regardless of the TEC level. In contrast, coalescence of the polymer particles in the film coating process was enhanced with higher levels of TEC, as demonstrated by scanning electron microscopy (SEM). The addition of TEC (0% to 8%) in the IDM hot-melt extrudate formulation had no influence on the drug release rate as the drug release rate was controlled by drug diffusion through the inside of the polymeric materials rather than between the polymer particles.     

Formulation and stability study of chlorpheniramine maleate nasal gel

Nasal administration has been of special interest in the last decade due to its feasibility and relative high bioavailability compared to the oral rout of administration. Our study aimed to develop a nasal gel formulation for an antihistaminic drug, Chlorpheniramine maleate (CPM), which suffers from poor oral bioavailability (25–45%) due to its first-pass metabolism in the liver. Different formulations of CPM nasal gels were prepared using different polymers in different concentrations, these gels were evaluated for their in vitro (physico-chemical properties, release, permeability and stability) to select the best formulation which subject to in vivo tests including mucociliary clearance and bioavailability, both in comparison to the solution and commercial tablet Allergyl^®.     

The effects upon vigilance and reaction speed of the addition of ephedrine hydrochloride to chlorpheniramine maleate

Summary The addition of the stimulant, ephedrine hydrochloride (15 mg), to the antihistamine, chlorpheniramine maleate (10 mg) is shown significantly to reduce the adverse drowsy effects of the latter upon various components of human performance. Auditory vigilance — a test of long-term attentiveness — is shown particularly to benefit from the addition of ephedrine. Whilst ephedrine does not aid simple reaction speed, it does reduce the pausing in serialchoice performance, indicative of a drowsy state, which otherwise occurs under chlorpheniramine alone.     

扑尔敏和息斯敏对大鼠及家兔离体子宫收缩的抑制作用

扑尔敏和息斯敏对缩宫素、前列腺素（ＰＧＦ２α）所致大鼠、家兔离体子宫平滑肌收缩均有明显的抑制作用，并使其张力降低，对它们的自发性收缩也具有同样作用，呈明显剂量依赖性，在较大剂量下（扑尔敏７．８×１０－４ｍｏｌ／Ｌ息斯敏１×１０－４ｍｏｌ／Ｌ）可完全取消缩宫素（５Ｕ／Ｌ）、ＰＧＦ２α（１×１０－６ｍｏｌ／Ｌ）诱发的子宫收缩，并使子宫静息能力降至最低点。以上作用可能是由于对于子宫平滑肌直接作用所致。     

Comparative study of acute effects of single doses of fexofenadine, olopatadine, d-chlorpheniramine and placebo on psychomotor function in healthy volunteers

Since most classical (first-generation) antihistamines have undesirable sedative effects on the central nervous system (CNS), newer (second-generation) antihistamines have been developed to relieve the sedative effects and to improve the patient's quality of life. However, the psychomotor profiles of second-generation antihistamines are not fully elucidated. In this randomized, double-blind, crossover study, the acute effects of single doses of second-generation antihistamines, fexofenadine (120 mg) and olopatadine (10 mg), on cognitive and psychomotor performance were investigated in comparison with those of placebo and d-chlorpheniramine (4 mg), a first-generation antihistamine, using objective and subjective assessments, in 11 healthy Japanese volunteers. In a battery of psychomotor tests, d-chlorpheniramine impaired tracking ability in the compensatory tracking task and caused a reduction in behavioural activity as continuously measured by wrist actigraphy. Olopatadine, like d-chlorpheniramine, reduced the behavioural activity, while fexofenadine had no effect in any of the tests. No significant changes in the subjects' self-ratings of drowsiness were found with the three antihistamines. These results suggest that d-chlorpheniramine and olopatadine, but not fexofenadine, produce sedative effects on psychomotor performance, and that the CNS profile of fexofenadine is different from that of olopatadine.     

Chlorpheniramine. II. Effect of the first-pass metabolism on the oral bioavailability in dogs

The pharmacokinetics of chlorpheniramine has been studied in six dogs by following the time course of plasma concentration of the drug after intravenous and oral administration of its maleate salt in solution form. After intravenous dosing the decline in chlorpheniramine plasma concentration was typically biexponential. The drug distributed rapidly and extensively to the extravascular tissues. The mean distribution phase halflife was 12.5 min, and the mean apparent volume of distribution, Vd, was 525% ofthe body weight in four dogs with normal hematocrits. The mean half-life of elimination was 1.7hr. The percent absolute availability following oral administration of the drug in the aqueous solution form was found to be dose dependent. At 100-mg dose, in six dogs, an average of 36% of the orally administered dose was found to be systemically available. At 50-mg dose, in one of the four dogs studied, no measurable plasma levels of chlorpheniramine were obtained, and the average bioavailability was only 9.4%. The average availability in four dogs at 200-mg dose was 39.4%. Even at 200-mg oral dose, the dogs did not show any signs of sedation and remained alert all through the experiment. Saturable first-pass gut and/or hepatic elimination has been postulated. The possible implications of these findings on the therapeutic effectiveness of the usual dosing regimen of chlorpheniramine in dogs are discussed.     

UPLC-MS/MS法快速测定中药及保健食品中非法添加17种抗炎镇痛类化学药的研究

目的建立一种快速、准确检测中药及保健食品中非法添加17种抗炎镇痛类化学药(对乙酰氨基酚、阿司匹林、非那西丁、马来酸氯苯那敏、罗非昔布、吡罗昔康、氯诺昔康、美洛昔康、醋酸泼尼松、舒林酸、萘普生、醋酸地塞米松、保泰松、奥沙普秦、塞米昔布、双氯芬酸钠、吲哚美辛)的方法。方法采用UPLC-MS/MS法,以Waters Acquity BEH-C18柱(100 mm×2.1 mm,1.7μm)为色谱柱,以0.1%甲酸甲醇溶液(A)-0.1%甲酸水溶液(B)为流动相,梯度洗脱:0~4 min,40%A;4~5 min,40%~50%A;5~6 min,50%~60%A;6~12 min,60%~80%A;12~13 min,80%A;13~14 min,80%~40%A;体积流量0.2 m L/min,柱温40℃。选择ESI离子源、多反应监测(MRM)模式测定17种临床常用的抗炎镇痛类化学药,通过比较MRM通道中样品峰与对照品峰的分子离子峰、二级碎片离子峰、色谱保留时间等信息确定添加的化学药物,并根据外标法以质谱峰面积计算添加药物的准确量。结果在上述色谱及质谱条件下,对乙酰氨基酚、阿司匹林、非那西丁、马来酸氯苯那敏、罗非昔布、吡罗昔康、氯诺昔康、美洛昔康、醋酸泼尼松、舒林酸、萘普生、醋酸地塞米松、保泰松、奥沙普秦、塞米昔布、双氯芬酸钠、吲哚美辛17种化学药物的分离度良好,方法检测限(LOD)均在0.3~5.0 ng/g,定量限(LOQ)均在0.9~15.0 ng/g,加样回收率均在90.5%~113.8%。样品中检出了对乙酰氨基酚、醋酸泼尼松、双氯芬酸钠、吲哚美辛、马来酸氯苯那敏、萘普生。结论方法简便、准确,灵敏度高,可作为抗炎镇痛类中药及保健食品中非法添加化学药的定性定量测定方法。     

络合萃取-分光光度法测定复方解热凝胶中马来酸氯苯那敏含量

创立了测定复方解热凝胶中马来酸氯苯那敏含量的络合萃取 分光光度法．实验表明,马来酸氯苯那敏在８ ～１８ μｇ／ｍＬ范围内呈现良好的线性关系．Ａ＝ ０－０４３ ８ Ｃ－ ０－０１６ ６ ,ｒ＝ ０－９９９ ７（ ｎ ＝ ５）,ＲＳＤ 为０－７４ ％ ,回收率９９－９ ％ ．