枢复宁在肺癌患者体内的药物动力学和生物利用度

９名接受顺铂化疗的原发性肺癌患者单次口服和静脉注射枢复宁８ｍｇ后，用反相高效液相色谱法测定血浆药物浓度。经用ＰＫＢＰ－Ｎ１程序在计算机上拟合计算表明，枢复宁在人体内表现为二房室模型。口服后主要药动学参数：Ｔ１／２Ｋａ＝０．４１±０．３０ｈ，Ｔ１／２α＝０．９±０．４３ｈ，Ｔ１／２β＝３．３±１．２ｈ，Ｃｍａｘ＝２８．６±９．５ｎｇ／ｍｌ，Ｔｍａｘ＝１．７±０．９ｈ，ＡＵＣ＝１５８±７３ｎｇ·ｈ／ｍｌ，绝对生物利用度为５５％。     

翁丹西隆的合成

以环己酮为起始原料,经与苯肼缩合、氧化、Mannich 反应制得1,2,3,9-四氢-3-二甲胺基甲基-4H-咔唑-4-酮盐酸盐(5),后者再与2-甲基咪唑缩合、甲基化合成翁丹西隆,总收率为10.4%。     

盐酸蒽丹西酮合用地塞米松对顺铂所致家犬的止吐作用

家犬静脉注射顺铂造成呕吐模型,分别用盐酸蒽丹西酮、盐酸蒽丹西酮加地塞米松进行止吐作用的观察。0.2mg/kg盐酸蒽丹西酮仅有部分止吐作用,无论0.5mg/kg和0.2mg/kg的地塞米松均无任何止吐作用,而两者合用时,止吐作用大大增强,0.2mg/kg盐酸蒽丹西酮加0.2mg/kg地塞米松,可达到完全控制顺铂所致的恶心、呕吐。     

高效液相色谱法测定人血浆中翁丹西隆浓度

建立了翁丹西隆的高效液相色谱测定法。血浆样品用醋酸乙酯萃取，以ＺｏｒｂａｘＳｉｌｉｃａ为固定相，６０％０．０２５ｍｏｌ／Ｌ乙酸钠缓冲液（ｐＨ４．２）、４０％乙腈为流动相，紫外３１０ｎｍ处测定。采用外标法峰高定量。最低检出浓度达１ｎｇ／ｍｌ，线性范围１．０～４０．０ｎｇ／ｍｌ（ｒ＝０．９９９６），平均回收率为（９５．２２±３．５８）％（ＲＳＤ３．７６％）。用本法测定人血浆中翁丹西隆浓度具有快速、简便、专一性和灵敏度高的优点。     

自拟人参二苓解毒汤联合盐酸恩丹西酮注射液治疗顺铂引起恶心呕吐临床观察

[目的]探讨顺铂引起恶心呕吐的有效治疗途径。[方法]对肺癌患者64例,随机分2组。自拟人参二苓解毒汤联合盐酸恩丹西酮注射液(以下简称商品名欧贝)(B组)和单独使用欧贝(A组)对顺铂为主的静脉化疗后镇吐疗效。[结果]B组(78·13%,93·75%)较A组(59·38%,75·00%)在近期镇吐治疗(指化疗后24-48h出现恶心呕吐)有明显差异(P<0·05),并在副作用方面,如便秘,乏力症状和血三系下降有明显差异(P<0·05)。[结论]辅以自拟人参二苓解毒汤确有增效解毒功能。     

Efficacy of ondansetron and metoclopramide for preventing postoperative emesis following strabismus surgery in children

A double-blind, randomised, placebo-controlled trial was conducted to compare the efficacy of metoclopramide with the 5-HT₃ antagonist, ondansetron, for the prevention of postoperative emesis in children undergoing elective strabismus surgery. None of the children received any premedication and a similar anaesthetic technique was used for all. Ondansetron 0.15 mg.kg⁻¹, metoclopramide 0.25 mg.kg⁻¹ or saline placebo were administered following intravenous catheter placement. Episodes of emesis were recorded for the first 24 h for the intervals of 0–2, 2–6 and 6–24 h. The incidence of emesis in the first 24 h was observed to be 71.7% in the placebo group, 34.4% in the ondansetron group (p < 0.001) and 61.4% in the metoclopramide group (p = NS). The severity of vomiting was less in the ondansetron group as compared with metoclopramide (p < 0.01) and placebo (p < 0.001). Recovery room scores were comparable in all the groups. No serious side-effects were observed in the ondansetron group. We conclude that prophylactic ondansetron is effective and superior to metoclopramide in the prevention of postoperative emesis in children following elective strabismus surgery.     

恩丹西酮预防椎管内阻滞后寒战的效果

①目的观察麻醉前静脉注射恩丹西酮预防椎管内阻滞后寒战的效果和对腋温的影响.②方法选择腰麻-硬膜外联合麻醉下行经腹全子宫切除术病人160例,随机分为两组,实验组(n=80)麻醉前静脉注射恩丹西酮8mg;对照组(n=80)麻醉前静脉注射生理盐水4mL,观察两组术中平均动脉压、心率、腋温变化和寒战发生情况.③结果实验组8例出现寒战(10.0%),对照组26例出现寒战(32.5%),两组比较差异有显著性(x2=7.05,P＜0.01).两组平均动脉压、心率、腋温变化差异无显著性(t=0.14～1.71,P均＞0.05).④结论恩丹西酮可预防椎管内阻滞后寒战的发生,但对腋温无影响.     

Mechanism of Intestinal Absorption of Ranitidine and Ondansetron: Transport Across Caco-2 Cell Monolayers

We have investigated the transport of ranitidine and ondansetron across the Caco-2 cell monolayers. The apparent permeability coefficients (P _app) were unchanged throughout the concentration range studied, indicating a passive diffusion pathway across intestinal mucosa. No metabolism was observed for ranitidine and ondansetron during the incubation with Caco-2 cell monolayers. P _app values for ranitidine and ondansetron (bioavailability of 50 and 100% in humans, respectively) were 1.03 ± 0.17 × 10^–7 and 1.83 ± 0.055 × 10^–5 cm/sec, respectively. The P _app value for ranitidine was increased by 15- to 20-fold in a calcium-free medium or in the transport medium containing EDTA, whereas no significant change occurred with ondansetron, indicating that paracellular passive diffusion is not rate determining for ondansetron. Uptake of ondansetron by Caco-2 cell monolayers was 20- and 5-fold higher than that of ranitidine when the uptake study was carried out under sink conditions and at steady state. These results suggest that ranitidine and ondansetron are transported across Caco-2 cell monolayers predominantly via paracellular and transcellular pathways, respectively.     

Oral ondansetron decreases vomiting after tonsillectomy in children

Vomiting is a common, unpleasant aftermath of tonsillectomy in children. Intraoperative intravenous ondansetron (OND) reduces vomiting after this operation. Our doubleblind, placebocontrolled, randomized investigation studied the effect of the oral form of OND on vomiting after outpatient tonsillectomy in children. We studied 233 healthy children age 2–14 yr undergoing elective tonsillectomy. Subjects were given placebo (PLAC) or OND 0.1 mg · kg^?1 rounded off to the nearest 2 mg one hr before surgery. Anaesthesia was induced with either propofol or halothane/N₂O. Vecuronium 0.1 mg · kg^?1 was administered at the discretion of the anaesthetist. Anaesthesia was maintained with halothane/N₂O, 50 μg · kg^?1 midazolam iv and 1–1.5 mg · kg^?1 codeine im. At the end of surgery, residual neuromuscular blockade was reversed with neostigmine and atropine. All episodes of inhospital emesis were recorded by nursing staff. Rescue antiemetics in the hospital were 1 mg · kg^?1 dimenhydrinate ivfor vomiting × 2 and 50 μg · kg^?1 droperidol iv for vomiting × 4. Parents kept a diary of emesis after discharge. Postoperative pain was treated with morphine, codeine and/or acetaminophen. The two groups were similar with respect to demographic data, induction technique and anaesthesia time. Oral OND (n = 109) reduced postoperative emesis from 54% to 39%, P < 0.05. This effect was most dramatic inhospital, where 10% of the OND-patients and 30% of the PLAC-group vomited, P < 0.05. The OND-subjects required fewer rescue antiemetics, 7% vs 17%, P < 0.05. In conclusion, oral ondansetron decreased the incidence of vomiting after outpatient tonsillectomy in children.