Single-dose pharmacokinetics of paracetamol and its conjugates in Chinese non-insulin-dependent diabetic patients with renal impairment

Objective: A single oral dose of paracetamol (20 mg · kg⁻¹) was given to 38 Chinese patients with non-insulin-dependent diabetes mellitus (NIDDM) who had either normal renal function or varying degrees of renal impairment, with creatinine clearances ranging from 4 to 123 ml · min⁻¹ · 1.73 m⁻². The plasma and urinary concentrations of paracetamol and its major metabolites were measured by high-performance liquid chromatography (HPLC). Results: The absorption and elimination of paracetamol were unaffected by renal impairment. However, the area under the plasma concentration time curve and the elimination half-life of paracetamol metabolites increased significantly with worsening renal insufficiency. Mean renal clearances of paracetamol and its conjugates were significantly reduced in these subjects. There was no evidence of altered metabolic activation with renal impairment. Conclusion: The results demonstrate that paracetamol disposition is minimally affected by diabetic nephropathy; however, extensive accumulation of conjugates may occur. Received: 2 September 1996 / Accepted in revised form: 11 December 1996     

氮酮对扑热息痛渗透裸鼠皮肤的促透作用

以裸鼠皮肤为隔膜的上下扩散的２个简单扩散小室研究氮酮对扑息痛透皮渗透促进作用。     

Acute effects of vitamin B6 and fixed combinations of vitamin B1, B6, B12 on nociceptive activity evoked in the rat thalamus: Dose-response relationship and combinations with morphine and paracetamol

Summary Nociceptive activity was elicited in neurones of the thalamus by supramaximal electrical stimulation of afferent C fibres in the sural nerve of rats under urethane anesthesia. The fixed combination of vitamin B₁, B₆, B₁₂ (Neurobion^®) as well as of vitamin B₆ administered by i.p. injection dose-dependently reduced the evoked nociceptive activity. The ED₅₀ of Neurobion^® is 4.6 ml/kg (at 100 min after injection) and that of vitamin B₆ is 189mg/kg (at 90 min after injection). The minimum effective doses of Neurobion^® and vitamin B₆ are 0.5 ml/kg and 40 mg/kg, respectively. When Neurobion^® or vitamin B₆ were given at their minimum effective doses, and the minimum effective doses of morphine (0.025 mg/kg) or paracetamol (5 mg/kg) were injected i.v. 80 min later, i.e., when the maximum effect of higher doses of Neurobion^® or vitamin B₆was about to develop, no supraadditive effect developed. It is concluded that the antinociceptive effect caused by a single injection of Neurobion^® is largely due to vitamin B₆. Vitamin B₁₂ may contribute to this effect, whereas vitamin B₁ alone exhibited only a slight effect on nociception. Moreover, it appears that Neurobion^® produces its antinociceptive effect after a single injection and after repeated administration during several days by different mechanisms so that the effect of analgesic agents is not enhanced following a single injection of Neurobion^® but may be enhanced after repeated administration of the compound.     

扑热息痛所致狗急性肝功能衰竭时血浆5-羟色胺变化及肝脏血流动力学改变的实验研究

目的;通过扑热息痛所致急性肝功能衰竭的动物模型,以期探讨门静脉,肝静脉,腹主动脉,下腔静脉血浆５－羟色胺浓度变化和肝脏血流动力学改变。方法：成年杂种狗１２只,在戊巴比妥钠静脉麻醉下,作上腹正中切口,从门静脉,肝静脉,腹主动脉,下腔静脉各采血２ｍｌ,作血浆５－羟色胺含量检测,作楔形肝组织活检,关腹。     

A review of the hepatotoxicity of paracetamol at therapeutic or near-therapeutic dose levels, with particular reference to alcohol abusers

The number of published reports associating hepatotoxicity with paracetamol ingestion at therapeutic or near-therapeutic dose levels is small but is, nevertheless, suggestive of a relationship. There is however, mounting evidence that certain groups of patients, such as alcohol-dependent people, patients receiving enzyme-inducing drugs (particularly anti-convulsant and anti-tuberculosis medications) as well as those with certain infectious diseases, are rendered more susceptible to paracetamol-induced hepatotoxicity. Seventy-four case reports where therapeutic or near-therapeutic doses of paracetamol resulted in hepatic injury are reviewed and factors and mechanisms which might explain this apparently increased vulnerability to damage are discussed.     

紫外分光光度法测定氨咖黄敏片中对乙酰氨基酚含量

目的：建立测定氨咖黄敏片中对乙酰氨基酚的紫外分光光度法.方法：采用氢氧化钠溶液为溶剂,在257nm波长处测定吸收度,绘制标准曲线.结果：该法测定平均回收率为99.8%,RSD为0.28%,线形范围为4.8～11.2μg/ml,r=0.9999.结论：该分析方法是一种灵敏,准确和简便的分析方法.     

布洛芬和对乙酰氨基酚在小儿呼吸系统感染性发热中的疗效分析

目的:探讨布洛芬和对乙酰氨基酚在小儿呼吸系统感染性发热中的疗效分析。为临床医师用药提供参考。方法:对我院2003年10月￣2004年6月因呼吸系统感染性发热住院的患儿,对于体温≥38.5℃者随机应用布洛芬64例和对乙酰氨基酚60例,对其进行退热疗效分析。结果:布洛芬组在最大作用时间及持续时间上,明显大于对乙酰氨基酚组,两组比较有显著性差异,P<0.01。结论:口服布洛芬退热效果确切,且明显优于对乙酰氨基酚,具有较强而持久的疗效。在儿科布洛芬作为解热药使用是安全、有效而且疗效持久的。     

When Fever, Paracetamol? Theory and Practice in a Paediatric Outpatient Clinic

Objective: To determine how medical and nursing staff treat feverish children and compare the findings with their theoretical knowledge, evaluating how they might contribute to fever phobia in parents.Setting: Paediatric Emergency Department.Method: In the first step, we analysed prospectively the files of all children having consulted the Paediatric Emergency Department with a history of fever or of body temperature above 38 °C during a 2-week period. The second step consisted of evaluating knowledge and perception of fever of doctors and nurses using a questionnaire.Main outcome measures: Prospective study: final diagnosis (viral, non- invasive bacterial disorders, invasive bacterial disorders), site of measurement and average temperature. Evaluation of theoretical knowledge: definition of fever, site of measurement, evaluation of the child’s clinical state, antipyretic drug choice.Results: A total of 114 children under 5 years of age were enrolled and 24 caregivers (12 doctors, 12 nurses, 90 of the staff) responded to the questionnaire. The results showed good consistency in theoretical knowledge, but an excessive fear about cerebral damage was also shown by doctors. This belief likely contributes to the transmission of fever phobia to parents. In contrast, analysis of children management showed that fever was often under-treated, especially by nurses and even more so by parents. Paracetamol remained the first-line antipyretic drug yet was often administered in insufficient doses. Non-steroidal anti-inflammatory drugs were seldom used, except by parents (16 of all the children). Contrary to literature, the favourite route of administration was the rectal one. Physical methods like sponging were largely used by nurses, despite the uncertainties in their real effectiveness and their known side-effects.Conclusion: Our study showed that the management of feverish children was globally correct in the Paediatric Emergency Department, but several improvement measures have been taken (e.g. tables of normal and abnormal ranges of temperature, recommended temperature measurement techniques, dosage regimen of antipyretic drugs, guidelines to parents), justifying the implementation of a pharmaceutical follow-up.