市场上部分小儿氨酚黄那敏颗粒的质量调研

目的调研现市场上小儿氨酚黄那敏颗粒中对乙酰氨基酚和马来酸氯苯那敏的含量均匀度,考察该产品的质量情况。方法通过抽查现市场上8个小儿氨酚黄那敏颗粒产品,采用高效液相色谱法（HPLC）同时测定对乙酰氨基酚和马来酸氯苯那敏的含量均匀度。结果以对乙酰氨基酚和马来酸氯苯那敏的含量均匀度为衡量标准,有7个产品的对乙酰氨基酚的均匀度合格;有1个产品马来酸氯苯那敏的均匀度合格。结论所抽查的小儿氨酚黄那敏颗粒质量只有1个达到合格要求。     

A pharmacokinetic study investigating the rate of absorption of a 500 mg dose of a rapidly absorbed paracetamol tablet and a standard paracetamol tablet

ABSTRACT

Objective: A rapidly absorbed tablet formulation of paracetamol containing sodium bicarbonate (PS) has been previously shown to be absorbed at least twice as fast as a standard paracetamol tablet (P) at a 1?g dose. In South America and Asia it is customary for patients to take a 500?mg dose of analgesic. The objective of this pharmacokinetic study was to compare the rate of absorption of PS versus P at a 500?mg dose.

Research design and methods: An open, randomized, single dose, cross-over study. Thirty Hispanic healthy volunteers randomly received a 500?mg dose taken orally with 50?mL of water 2?h after a standard breakfast. Blood samples were taken up to 10?h post-dose. Plasma concentrations of paracetamol were determined by HPLC with UV detection.

Main outcome measures: AUC_{0–30 min}, C_{plasma 30 min} and T_max were analyzed non-parametrically by the Wilcoxon's rank sum test. A linear mixed effects model was used to analyze the logarithmically transformed AUC_0–∝ and C_max. Bioequivalence was accepted if the 90% confidence intervals (CI) for the ratio of the means of the primary pharmacokinetic variable AUC_0–∝ lay completely within the range 0.80–1.25.

Results: AUC_{0–30 min} and C_{plasma 30 min} were significantly greater and T_max was significantly shorter (all p < 0.0001) for PS versus P. The formulations were bioequivalent for AUC_0–∝ (90% CI 0.99:1.05) and no statistical difference was seen for C_max (95% CI 0.91:1.14).

Conclusions: Paracetamol was absorbed at least twice as fast from PS compared to P at a 500?mg dose. The extent of absorption was equivalent for both formulations.     

Analgesia following oral surgery for day patients a clinical comparison of two analgesics

Summary

A single-blind, between-patient study was carried out in 167 patients following oral surgery to compare the effectiveness and tolerance of two combination analgesic preparations/pentazocine (15?mg) plus paracetamol (500?mg) and dextropropoxyphene hydrochloride (32.5?mg) plus paracetamol (325?mg). Assessments of pain and pain relief were made over two periods, initially over the 90 minute period following administration of either preparation and secondly, over the subsequent 3 days following discharge. At the hospital, those patients receiving pentazocine plus paracetamol achieved a greater relief of pain than those receiving dextropropoxyphene plus paracetamol, though the differences did not reach statistical significance. At home,pain relief was very similar for both groups of patients, both preparations being effective and well tolerated.     

Semiological evaluation of pain according to its origin: a prospective,observational, and national study of current French medical practice

Abstract

Objective:

To determine how the origin of acute pain influences its semiological characteristics, and to evaluate the efficacy and safety of two Level 2 analgesic combinations in general practice.     

氨酚曲马多治疗陆军驾驶兵下腰痛的疗效分析

目的评价氨酚曲马多治疗陆军驾驶兵下腰痛的临床疗效。方法 2010年3月-2012年3月在我院门诊就诊下腰痛驾驶兵360例,应用氨酚曲马多治疗,于治疗后第1、2、4周分别应用视觉模拟评分（VAS）和Oswestry功能障碍指数（ODI）评价疗效。结果治疗1、2、4周后,所有患者临床症状均不同程度改善。VAS评分及ODI在治疗1、2、4周后均较治疗前明显下降,差异有统计学意义（P〈0.05）,但治疗后1、2、4周之间比较差异无统计学意义（P〉0.05）。结论氨酚曲马多可显著缓解下腰痛,提高驾驶兵伤病员的战斗力及生活质量。     

Thermoresponsive Drug Delivery Using Liquid Crystal-Embedded Cellulose Nitrate Membranes

The aim of this study was to investigate the use of thermotropic liquid crystalline (TLC) blends of 4-pentyl-4′-cyanobiphenyl (K15) and 4-heptyl-4′-cyanobiphenyl (K21) with appropriate nematic to isotropic phase temperature (T_{n ? i}) just above body temperature as a temperature-modulated drug permeation system. Using differential scanning calorimetry (DSC) we showed that the phase transition temperature (T_{n ? i}) of K15 and K21 were 34.2°C and 41.5°C respectively. However, the thermogram of K15 and K21 blends with different ratios was shown to be a single endothermic peak similar to that of pure TLCs. K15 and K21 blends did not behave as a physical blend of two thermotropic liquid crystals with different T_{n ? i}. However, they are rather mixed together in such ways that behave like a single unit TLC. The T_{n ? i} of these TLC mixtures was linearly proportionate to the ratio of K15:K21. Using appropriate ratio of K15:K21 TLC, a mixture with desirable phase transition temperature was obtained. A triple layer of cellulose nitrate membranes containing a 50:50 mixture of K15 and K21 was used for drug permeation studies. This composite membrane showed good pulsatile permeation of drug molecules in response to temperature changes below and above the T_{n ? i} of the K15 and K21 blends in a reproducible and reversible manner. Paracetamol and methimazole were chosen as hydrophobic and hydrophilic drug models, respectively. Methimazole permeability through the TLC membrane was much higher (36.0 × 10^?5 cm/s) at temperatures above the phase transition temperature of liquid crystal blends than that (7.2 × 10^?5 cm/s) at temperatures below the phase transition temperature of liquid crystal blends (38.1°C).     

氨咖愈敏溶液中对乙酰氨基酚、愈创甘油醚、咖啡因、马来酸氯苯那敏含量测定方法的研究

目的研究分析氨咖愈敏溶液含量测定方法,优化色谱分离条件。方法采用C18柱,流动相为磷酸二氢铵溶液-乙腈-甲醇（70：10：20）,检测波长为271nm,测定对乙酰氨基酚、愈创甘油醚、无水咖啡因含量;采用C18柱,流动相为磷酸二氢铵缓冲液（0．1％三乙胺）-乙腈（73：27）,检测波长为221nm,测定马来酸氯苯那敏含量。结果对乙酰氨基酚、愈创甘油醚、咖啡因分别在0．03051～0．3051mg／ml（r=1）、0．009748～0．09748mg／ml（r=1）、0．003838～0．03838mg／ml（r=1）与峰面积有良好的线性关系,平均回收率分别为101．5％、100．6％、100．7％（n=9）,马来酸氯苯那敏在0．003968～0．03968mg／m]（r=1）与峰面积有良好的线性关系,平均回收率为100．1％（n=9）。结论该方法操作简便、准确、重复性好,可用于氨咖愈敏溶液的质量控制。     

A descriptive analysis of aspartate and alanine aminotransferase rise and fall following acetaminophen overdose

Context: Risk prediction following acetaminophen (paracetamol, APAP) overdose is based on serum APAP, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels. One recently proposed risk stratification tool, the APAPxAT multiplication product, uses either AST or ALT, whichever is higher, yet their interrelation is not well known following APAP-induced hepatic injury. Objective: To describe the kinetics of AST and ALT release into and disappearance from the circulation following APAP overdose. Materials and Methods: An observational case series of adult patients with peak AST or ALT > 100 IU/L attributable to APAP toxicity. Cases were identified by electronic search of hospital laboratory database and by discharge diagnosis corroborated by structured explicit medical record review. Results: Of 68 cases identified (mean age (SD): 39 (18) years, 63% female, and 21% ethanol co-ingested), 28 (41%) developed hepatotoxicity (peak AST or ALT > 1000 IU/L), 28 (41%) coagulopathy (international normalized ratio or INR > 2), and 21 (31%) both. Three patients (4%) were transferred for liver transplantation and ultimately six (8.8%) died. Serum AST and ALT activity rose in a closely aligned 1:1 AST:ALT ratio, but fell at distinctly different rates: AST activity fell with a half-life (interquartile range [IQR]) of 15.1 (12.2, 19.4) hours, and ALT 39.6 (32.9, 47.6) hours. Using an aminotransferase falling to below 50% of peak as the basis for discontinuing acetylcysteine would have resulted in antidotal treatment being stopped 24 (IQR: 9.6, 40) hours earlier (and in no cases later) using AST rather than ALT. Only six patients had an AST:ALT ratio greater than 2:1 at the time of acetylcysteine administration; of these six, four died and one survivor developed coagulopathy. Discussion: AST and ALT release into the circulation appears tightly linked and numerically similar, except in the sickest patients. Once the aminotransferases peak, AST returns to baseline more quickly. Conclusion: Either AST or ALT can be used for early risk stratification tools when only one is known. Any criterion for N-AC discontinuation should be based on the decline of AST rather than ALT, with a potential benefit measured in days.     

Early acetaminophen-protein adducts predict hepatotoxicity following overdose (ATOM-5)

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Paracetamol poisoning in children

Paracetamol (acetaminophen) has become an antipyretic drug of choice. Due to its widespread use, toxicity secondary to overdose has increased in recent years. Children are especially vulnerable to accidental exposure due to non availability of child proof containers in India. The main clinical features of acute toxicity include anorexia, vomiting, abdominal pain, jaundice, hematuria and metabolic acidoses. Diagnosis is based on history and laboratory findings of acidosis and abnormal liver function tests. N-acetylcysteine is the specific antidote. This article reviews in detail the toxicokinetics, pathophysiology, clinical features and management of paracetamol poisoning in children.