Codeine-induced histamine release in intact human skin monitored by skin microdialysis technique: comparison ofintradermal injections with an atraumatic intraprobe drug delivery system

Background The skin microdiallysis technique makes it possible to measure histamine release in intact human skin in vivo directly. In this study we have used the microdialysis technique to characterize histamine release by codeine after intracutaneous injectioin and following skin challenge by a novel atraumatic delivery technique. Objective The purpose of the study was to compare histamine release in human skin by codeine. delivered by an intraprobe drug delivery system (IPD) and intracutaneous injections (ICT), with respect to dose-response relations, kinetics of histamine appearance and decay, corelations between histamine release and skin respones, and reproducibility. Methods Hollow dialysis fibres were inserted intradermally in 12 healthy subjects. Twelve fibres were inserted in each subjects, six fibres in each arm. Each fibre was perfused at a rate of 3 μL/min, and samples were collected in 2 min fractions. By the IPD technique, codeine was administrered to the skin by adding codeine to the perfusion medium. Sequential IPD challenges were performed in one arm. and ICTs were done on the other arm. Results Sixfold serial dilutions of codeine (0.01-3 mg/mL) caused a significant doserelated histamine release by ICT and IPD. Peak histamine release was found within the first 4 min after skin challenge by ICT and IPD, followed by a fast decline with a dialysate histamine half life of approximately 2-3 min. Peak hisamine release was linearly correlates with cumulative release of the 20 min sampling period, and histamine release correlated with weal soze. The coefficient of variation on peak histamine releae was 18.9% and 4.8% for codeine ICT and IPD, respectively. Conclusioin We have described in detail codeine-induced histamine release in intact human skin in vivo by the microdialysis technique. It was possible to administer codeine atraumaticallyl to the skin by intraprobe delivery. The skin microdialysis codeine atraumaticallly to the skin by intraprobe delivery. The skin microdialysis technique opens up possibilities for measurement of infllammatory mediators release in normal and diseases skin, and it will be possible to deliver immunopharmacologically active drugsto the skin by intraprobe delivery.     

反相高效液相色谱法测定阿司匹林可待因片中磷酸可待因和阿司匹林的含量

目的：建立一种用高效液相色谱法检测复方制剂中磷酸可待因和阿司匹林含量的方法。方法：用Ｃ１８ＯＤＳ为固定相。甲醇－００３ｍｏｌ·Ｌ－１醋酸钠（用冰醋酸调ｐＨ至３５）（１∶２５）为流动相。ＵＶ检测波长２８０ｎｍ。结果：该方法回收率为磷酸可待因１００４％,ＲＳＤ＝１３％（ｎ＝６）;阿司匹林９９４％,ＲＳＤ＝０９８％（ｎ＝６）。结论：该法不需经提取分离,溶解后直接进样。简便、快速,准确可靠,适合于生产中使用。     

奥亭止咳露与复方可待因口服溶液对照治疗121例患者的疗效

目的:评价奥亭止咳露临床镇咳、祛痰效果及不良反应.方法:采用随机双盲对照试验,可评价121例患者,分为试验组60例和对照组61例.试验组用奥亭止咳露每次15mL,po,tid,对照组用复方可待因口服溶液每次15mL,po,tid,2组均连用3～7d.结果:试验组镇咳临床总有效率为90%,对照组为74%,组间差异无显著性(P＞0.05).主要不良反应有头晕、嗜睡、口干、乏力、恶心、便秘、排尿困难等.结论:奥亭止咳露用于镇咳祛痰安全有效.     

可待因及羟考酮、右丙氧芬复方制剂依赖性的流行病学调查

目的 :调查评价 7种可待因及羟考酮、右丙氧芬复方制剂 (以下简称可待因复方制剂 )的依赖性。方法 :采用“回顾性调查”和“集中监测”相结合的调查方法 ,用自拟“可待因及羟考酮、右丙氧芬复方制剂使用情况调查表” ,对北京、上海、天津和南昌四个城市 2 1家医疗单位就诊患者中使用可待因复方制剂的情况进行调查。结果 :在 3910例符合条件的使用者中绝大多数用于治疗各种原因引起的疼痛。 7个品种药品致欣快效应VAS值介于 0 0 0 - 0 0 4之间 ;除少数患者在停用可待因复方制剂后出现轻度戒断症状外 ,绝大多数患者无戒断症状发生 ,各项症状OWS平均分值介于 0 0 0 - 0 0 9之间 ;7种可待因复方制剂的平均日剂量随使用时间的延长均有所增加。结论 :医疗用途常规剂量使用可待因复方制剂依赖性潜力很低 ;长期使用后身体可产生一定程度的耐受性     

Codeine influences the serum and urinary profile of endogenous androgens but does not interact with the excretion rate of administered testosterone

Today's doping tests involve longitudinal monitoring of urinary steroids including the testosterone glucuronide and epitestosterone glucuronide ratio (T/E) in an Athlete Biological Passport (ABP). The aim of this study was to investigate the possible influence of short‐term use of codeine on the urinary excretion of androgen metabolites included in the steroidal module of the passport prior to and after the co‐administration with testosterone. The study was designed as an open study with the subjects being their own control. Fifteen healthy male volunteers received therapeutic doses of codeine (Kodein Meda) for 6 days. On Day 3, 500 mg or 125 mg of testosterone enanthate (Testoviron®‐Depot) was administered. Spot urine samples were collected for 17 days, and blood samples were collected at baseline, 3, 6, and 14 days after codeine intake. The circulatory concentration of total testosterone decreased significantly by 20% after 3 days' use of codeine (p = 0.0002) and an atypical ABP result was noted in one of the subjects. On the other hand, the concomitant use of codeine and testosterone did not affect the elevated urinary T/E ratio. In 75% of the individuals, the concentration of urinary morphine (a metabolite of codeine) was above the decision limit for morphine. One of the participants displayed a morphine/codeine ratio of 1.7 after codeine treatment, indicative of morphine abuse. In conclusion, our study shows that codeine interferes with the endogenous testosterone concentration. As a result, the urinary steroid profile may lead to atypical findings in the doping test.     

38例复方磷酸可待因溶液依赖临床特征分析

目的：探讨复方可待因溶液依赖者的临床特点。方法：对38例复方可待因溶液依赖者的临床资料进行回顾性分析。结果：本组全部为男性青少年，滥用诱因主要为受同伴影响，药物购自药店。初次滥用年龄17．9±3．7岁，初始滥用时患者多为学生。成瘾后平均滥用剂量410．5±206．2mg／d，滥用时间3．3±1．7年，平均曾滥用过2．3±1．3种其他物质。依赖者戒断症状较轻，但心理依赖较明显，较少躯体合并症，脱瘾治疗效果较好。结论：复方可待因溶液易为青少年无医疗目的滥用，并导致依赖综合征，应采取切实预防措施。     

柴胡清肺合剂治疗热咳98例

将 1 33例热咳患者随机分成两组 ,治疗组 98例予以柴胡清肺合剂治疗 ,对照组 35例予以复方可待因糖浆治疗 ,疗程均为 2周。结果 :治疗组总有效率为 94 8% ,对照组为 54 7% ,差异有显著性意义 (P <0 0 0 1 )。提示柴胡清肺合剂治疗热咳有待好疗效。