阿米卡星全日剂量单次用药治疗下呼吸道感染的评价

对３５例耳、肾功能正常的下呼吸道细菌感染患者采用阿米卡星全日剂量单次给药评价其临床疗效及不良反应。结果表明,单次用药疗效与二次用药比较无明显差异。单次用药治疗前、后肾功能无明显变化,２例患者出现听力下降,但２周内恢复正常。二次用药治疗后３例病人尿β２－微球蛋白（β２－ＭＧ）、血α１－微球蛋白（α１－ＭＧ）出现异常变化;２例出现感音神经性耳聋患者１月内未恢复正常。提示：在获得满意疗效的同时,为有效降低不良反应,１５ｍｇ／ｋｇ全日剂量单次用药对患者更为有利。     

大剂量阿米卡星致抽搐1例

1病例介绍患儿,男,40 d,因腹泻黄色稀水样便2 d,3或4次·d-1,量少,在医务室肌内注射硫酸阿米卡星2次,剂量分别为100和150 mg,第2次给予硫酸阿米卡星后出现抽搐,双眼球上翻,四肢颤动,速来我院儿科救治。肌内注射苯巴比妥0.1 g,抽搐缓解。后上述症状反复多次出现,经检查,婴儿嗜睡,前囟隆起、饱满。大便常规检查:黄色稀便,脂肪球(++)、脓球(-)、血尿素氮6.0 mmol·L-1、血二氧化碳含量24 mmol·L-1、血钾4.8mmol·L-1、血氯101 mmol·L-1、血钙2.7 mmol·L-1、血钠133mmol·L-1;脑脊液常规检查结果正常,氯化物无异常。诊断为药物中毒、中毒…     

阿米卡星剂量的合理性探讨

本文通过对１３例临床病人的阿米卡星血药浓度测定，显示０．４ｇ／ｄ分两次肌内注射或静脉滴注的用药方案达不到有效治疗浓度，需要改进，临床应严格掌握用药剂量及周期，避免引起耳肾毒性。建议临床加强治疗监测，合理设计给药方案，提高治疗质量。     

某院阿米卡星临床用药分析

目的:促进阿米卡星临床合理应用。方法:采用回顾性调查方法,对某院自2006年4月～2010年2月使用阿米卡星并进行血药浓度测定的30例住院患者的临床资料进行统计、分析,包括基础疾病、病原学培养及药敏试验结果、阿米卡星用法、用量、血药浓度测定时间、临床疗效、不良反应情况等。结果:患者使用阿米卡星后临床有效率为55.2%;住院患者使用阿米卡星的药量偏低,血药浓度测定值与参考值相比也偏低;使用阿米卡星治疗后未见不良反应发生。结论:应适当提高阿米卡星用量比例并严密监测阿米卡星的血药浓度,实现个体化给药,以提高临床用药的有效性与安全性。     

大剂量甲氨喋呤化疗毒副作用的观察

大剂量甲氨喋呤化疗毒副作用的观察史克倩葛珊妹为探讨难治性急性淋巴细胞白血病（ＡＬＬ）和恶性淋巴瘤的理想化疗方案，提高缓解率，延长生存期。近２０年来，大剂量甲氨喋呤（ＨＤ－ＭＴＸ）的应用引起国内外广泛的关注。为探讨该药大剂量的毒副作用及耐受情况，我...     

阿米卡星致抽搐1例

患者,女,21岁.因呕吐、腹泻1d就诊.自述1d前餐后3h感腹胀、恶心,后又出现腹痛、腹泻,半天内腹泻约7～8次,水样便,每次量约600～800mL,曾自服吡哌酸(剂量不详),效果不佳,后又出现里急后重、黏液便,急来校医院门诊部就医.     

阿米卡星致血尿1例

患儿男性 ,3 91 2 岁 ,于 2 0 0 1年 1 0月 2 6日因恶心呕吐、腹痛腹泻 2天 ,就诊本院。查体 :体温 37°C。神志清 ,全身皮肤黏膜未见黄染、出血点 ,浅表淋巴结无肿大 ,双眼睑无浮肿 ,心肺无异常 ,腹软平坦 ,上腹部及脐周有压痛 ,无反跳痛 ,肝脾未扪及 ,肾区无叩击痛 ,腹部无移动性浊音。辅助检查 :血常规 :WBC1 5.1× 1 0 9/ L,N0 .72 ,尿常规正常 ,粪常规镜检有脂肪球。门诊印象急性胃肠炎。给予阿米卡星 (丁胺卡那霉素 ) 0 .2 g+5%葡萄糖注射液 2 50 ml静滴 ,约 2小时患儿自觉有轻微尿痛 ,排出淡红色血尿 ,留取标本做尿常规检查 ,镜检…     

阿米卡星致失语瘫痪1例

患儿 ,男 ,8岁。因发热 2ｄ ,突然失语及四肢瘫痪 4ｈ入院。患儿 2ｄ前发热 ,Ｔ 39℃ ,伴轻咳。入院前 4ｈ在乡村医生处快速静脉滴注 1 0 %葡萄糖注射液 1 50ｍＬ +阿米卡星 [江苏板桥药业有限公司 ,批准文号 :苏卫药准字 (1 989)第 35681 4号 ] 0 .3ｇ,0 .5ｈ后患儿自诉头晕 ,30ｍｉｎ后突然失语、四肢瘫痪。患儿既往体健。体检 :Ｔ 37.9℃ ,Ｐ 76次·ｍｉｎ 1 ,Ｒ 2 1次·ｍｉｎ 1 ,ＢＰ 90 70ｍｍＨｇ(1ｍｍＨｇ=0 .1 33ｋＰａ)。神志清 ,面黄 ,口不紧 ,嘴角不斜 ,舌僵直 ,咽及声带无充血水肿 ,能听懂他人语言 ,说话时可见口腔缓慢运动…     

阿米卡星致粒细胞缺乏症1例

患者,女,39岁,因反复发热2月,于2009年10月9日入院。患者约2月前无诱因下,出现发热症状,偶咳,少量白痰,最高体温38．5℃,但无畏寒、胸闷、胸痛、咯血、盗汗等症状。曾查胸片提示：两下肺纹理增粗。心彩超：二尖瓣关闭不全（后叶脱垂）,我院间断予阿奇霉素、青霉素等治疗无效,于2009年9月28日至上海中山医院血培养：“草绿色链球菌”感染。     

肌肉注射硫酸阿米卡星致过敏性休克1例

患者(实习护生),女18岁.因上呼吸道感染在门诊给硫酸阿米卡星0.2 g im Bid.第2天该护生来我科实习,晨间护理后,请带教老师给肌注硫酸阿米卡星.带教老师询问病情及是否注射过此药,并按常规检查药品后给其注射此药.     

阿米卡星日剂量单次与分两次给药方案的体内药效及毒性比较

目的探讨日剂量单次与分两次给药方案对阿米卡星体内抗菌作用及耳、肾毒性的影响.方法1.药效学实验健康雄性豚鼠,以临床分离的铜绿假单胞菌经气管注入建立肺炎模型,随机分成日剂量单次给药组(OD)、日剂量分两次给药组(BID)(给予阿米卡星100mg/kg/d肌注)和对照组(C)(给予等量生理盐水肌注qd),共72h.观测体温、体重变化,查WBC和CRP,取感染豚鼠肺组织制成匀浆,定量培养后进行活菌计数.2.毒性实验健康雄性豚鼠,随机分成OD、BID和C组,给予阿米卡星200mg/kg/d肌注,共4w.测定血BUN、Cr、尿NAG酶并计算Ccr,制备肾组织HE染色的病理切片及电镜标本综合评定肾毒性;测定听性脑干反应阈值,结合琥珀酶杂色的耳锅铺片和扫描电镜观察耳蜗形态学变化,综合评价耳毒性.结果1.药效学实验治疗72h后OD和BID组的体温、体重减少量、WBC、CRP及肺组织匀浆活菌计数均显著低于C组(P＜0.05),但OD和BID两组间差异无统计学意义(P＞0.05).2.毒性实验OD组2周时的尿NAG酶和4周时的血BUD显著低于BID组(P＜0.05),4周时的Ccr显著高于BID组(P＜0.05),耳蜗外毛细胞缺失数显著少于BID组(P＜0.05).结论阿米卡星日剂量单次和分两次给药方案的体内抗菌作用相当,与日剂量分两次给药相比单次给药可降低耳、肾毒性.     

A comparison of the effects on intragastric acidity of bedtime or dinnertime administration of a once daily dose of famotidine

Summary In order to assess whether dinnertime administration of a once daily dose of famotidine is more advantageous than a bedtime dose in suppressing evening and nocturnal gastric acidity, we gave nine patients with a past history of duodenal ulcer in double-blind, randomized fashion either (1) placebo at 6 p.m. and 10 p.m., (2) famotidine 40 mg at 6 p.m. (Fam 6) + placebo at 10 p.m. or (3) placebo at 6 p.m. + famotidine at 10 p.m. (Fam 10) on three separate occasions.Comparison of the 24-h median pH values showed that the two administrations of famotidine were superior to placebo, while Fam 6 was significantly more effective than Fam 10. The gain in acid suppression of Fam 6 with respect to Fam 10 was particularly evident from 6 p.m. to midnight.Although the antisecretory effectiveness of Fam 6 was lower than that of Fam 10 from 4 a.m. to 8 a.m., it remained clearly higher than that of placebo and ensured virtual anacidity (median pH=6.7) even in this time segment.We conclude that a once daily dose of famotidine at 6 p.m. is better than bedtime administration at covering the long period of continuous unbuffered intragastric acidity which extends from after the evening meal to breakfast.     

Fibrate-associated adverse effects beyond muscle and liver toxicity

Fibrate derivatives have a 40-year history in the management of dyslipidemia. Although this class of drugs is generally well tolerated, several safety issues have arisen from their use. In the present article we review the literature describing side effects associated with the use of fibrates except for those that are liver and muscle related. These effects are less well known but are clinically relevant.     

13-week repeated dose toxicity study of l-tyrosine in rats by daily oral administration

To evaluate the potential toxicity of l-tyrosine, 4 groups of Crl:CD(SD) rats of both sexes were administered l-tyrosine in water suspension by gavage once daily for 13 weeks at doses of 0 (vehicle), 200, 600 or 2000 mg/kg bw/day. Findings related to l-tyrosine administration were as follows. Edema of the cornified layer at the limiting ridge or forestomach was seen in 600 mg/kg bw/day female group and in both sexes of 2000 mg/kg bw/day group. In the liver, increased weight and hypertrophy of centrilobular hepatocytes were seen in both sexes at 2000 mg/kg bw/day, associated with slight increases in ALT and AST. Regarding the kidney morphology and function, increased hyaline droplets in the proximal tubules and increased urinary protein were seen in the 2000 mg/kg bw/day male group. In addition, increased kidney weight was also observed in both sexes of the 2000 mg/kg bw/day group, although the histological changes attributable to the weight increase remained unclear. As for blood chemistry, increases in triglycerides, total cholesterol, phospholipids, potassium ion, calcium, total protein, and α1 globulin were also seen in both sexes at 2000 mg/kg bw/day. Thus, in this study the no-observed-adverse-effect level (NOAEL) of l-tyrosine was considered to be 600 mg/kg bw/day for males and 200 mg/kg bw/day for females.     

较大剂量美托洛尔片治疗老年不稳定心绞痛的药物不良反应观察

目的 探讨较大剂量美托洛尔（抗心绞痛药）治疗老年不稳定心绞痛（UAP）心率减低时，可能出现的药物不良反应。方法 139例UAP患者，分为A、B2组，A组（69例）用美托洛尔每日174mg，心率：每分53次；B组（70例）用美托洛尔，每日131mg，心率：每分60次。分别观察1年内2组在心血管、代谢、中枢神经、肾功能等方面的药物不良反应。结果 2组均未发生因心律失常、低血压而停药者；但因心率而疑虑者A组为26人（38％），B组为11人（15％），2组经较差异显著。A组糖尿病调整剂量者为3例，B组为0；A组餐后血糖升高者为4例，B组为1例，差异均不显著。A组体重增加者2例，B组为0。结论 用较大剂量美托洛尔，使心率每分53次较心率60次，无明显副作用增加。     

Multiple dose pharmacokinetics of a new once daily extended release tolterodine formulation versus immediate release tolterodine

OBJECTIVE: To determine the multiple dose pharmacokinetics of a new extended release (ER) capsule formulation of tolterodine, compared with the existing immediate release (IR) tablet, in healthy volunteers. DESIGN: Nonblind, randomised, 2-way crossover trial. PARTICIPANTS: 19 healthy volunteers (7 females, 12 males), mean age 33 years (range 18 to 55 years). Prior to the study, all volunteers were classified as either extensive or poor metabolisers by cytochrome P450 2D6 genotyping. METHODS: Volunteers received tolterodine ER 4mg once daily or tolterodine IR 2mg twice daily for 6 days (all doses given as the L-tartrate salt). A washout period of 7 days separated the 2 treatments. Serum concentrations of tolterodine, its active 5-hydroxymethyl metabolite (5-HM) and the active moiety (extensive metabolisers: sum of unbound tolterodine + 5-HM; poor metabolisers: unbound tolterodine) were measured for up to 48 hours post-dose on day 6 (steady state). Tolerability was also determined. RESULTS: 17 volunteers (13 extensive metabolisers, 4 poor metabolisers) completed the study and were evaluable for both treatment periods. The 90% confidence interval for the geometric mean ratio of area under the serum concentration-time curve to 24 hours (AUC24) of the active moiety, for all volunteers combined, indicated equivalence for the 2 formulations. Pooled analysis also demonstrated that the peak serum concentration (Cmax) of the active moiety following administration of tolterodine ER was around 75% of that observed for the IR tablet, whereas the trough concentration was around 1.5-fold higher. Overall, the pharmacokinetics of tolterodine (irrespective of genotype) and 5-HM (extensive metabolisers only) were consistent with sustained drug release over 24 hours. Tolterodine ER was well tolerated. CONCLUSIONS: The new once daily ER formulation of tolterodine 4mg shows pharmacokinetic equivalence (AUC24) to the existing IR tablet given at a dose of 2mg twice daily. Findings of lower Cmax for tolterodine ER may explain the significantly lower rate of dry mouth subsequently observed in patients with overactive bladder.     

Antihypertensive effects of bisoprolol during once daily administration in patients with essential hypertension

Summary Biosprolol is a new beta₁-selective beta-blocking agent with a plasma half-time of 10–12 h and without partial agonist properties.Forty-eight patients with essential hypertension were randomly treated with 5, 10, or 20 mg bisoprolol given once daily for 8 weeks. All measurements were made 24 hours after the last dose.Bisoprolol had antihypertensive and beta-blocking properties both at rest and during exercise. The 20 mg dosage regimen was more effective than that of 5 mg and 10 mg.The drug was well tolerated and all the 48 patients completed the trial.     

Evaluation of once daily endralazine in hypertension

Summary Endralazine, a novel vasodilator related to hydralazine, exhibits a longer half-life and is only minimally influenced by acetylator status. The antihypertensive action of once daily endralazine has been studied in 17 patients previously controlled with an antihypertensive regimen which included hydralazine and a beta-blocker. Hydralazine was discontinued but other medications were unchanged. Pre-study dosage of hydralazine ranged from 25 mg b.i.d. to 50 mg g.i.d., mean daily dose 126.5 mg. End-ralazine was started at a dose of 10 mg o.d. and increased by 10 mg to a maximum of 40 mg o.d. until seated DBP was controlled below 95 mmHg. All 17 patients completed the study. Seated BP significantly decreased from 147.5/99.7 to 133.8/83.9 and standing BP from 145.8/99.2 to 133.6/87.3 mmHg. Ten patients (59%) were successfully controlled with endralazine once daily but 7 patients required twice daily dosage schedules because of lack of BP control at 24 h after dosing or excessive hypotension shortly after dosing. Other adverse effects were headache, palpitations and fatigue. There was a statistically insignificant average weight gain of 1 kg but pedal edema was not observed. Endralazine is an effective antihypertensive agent with adverse symptoms similar to those experienced with hydralazine.Presented in part at the 86th Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics, San Antonio, Texas, March 30, 1985     

Evaluation of once daily sotalol administration in man

1 Sotalol 400 mg orally was given to five healthy male volunteers as a single dose and then subsequently once daily for 8 days.

2 Following the single dose and again after the eighth daily dose, blood samples were obtained at 3, 7, 12, 24, 36 and 48 h for plasma sotalol estimation.

3 During the 8-day course of sotalol 400 mg once daily, the effect was assessed by exercise testing and blood samples drawn for plasma sotalol measurement at 0 and 3 h with each dose.

4 The elimination half-life after chronic administration (17.7 ± 2.6 h) was not significantly different from that obtained after the single dose (15.5 ± 1.2 h). No difference occurred either in the comparable plasma concentrations on both elimination curves. It would appear, therefore, that chronic administration of sotalol does not alter its kinetics.

5 Drug accumulation, measured as AUC_ss / AUC₁, showed a mean value of 0.95 ± 0.18, indicating that accumulation had not occurred.

6 Mean reduction of exercise heart rate ranged from a minimum of 20.5 ± 2.0% at time 0 on Day 8 to a maximum of 38.7 ± 1.1% at +3 h on Day 4. The minimum blockade in any individual during the 8 days was 14.5%.

7 There was a significant correlation between percentage reduction in exercise heart rate and plasma sotalol concentration.

8 Once daily administration of sotalol 400 mg orally would, therefore, appear to be an effective therapeutic regimen when sustained β-adrenoceptor blockade is required.