Mivacurium in infants and children

Mivacurium is the only available short-acting nondepolarizing muscle relaxant in clinical use. It is a bis-quaternary benzylisoquinolinium ester hydrolysed by plasma-cholinesterase into inactive compounds. The ED₅₀ and ED₉₅ in children are about 50 μg·kg^?1 and 90 μg·kg^?1 respectively. In infants, they have a tendency to be lower. A standard intubating dose of 0.25 mg·kg^?1 causes complete neuromuscular depression in 1.5–2 min, recovery to 5% in 6–10 min, and complete recovery in 15–20 min. The recent tendency is to use 0.3 mg·kg^?1 to obtain better intubating conditions with slight prolongation of effect. Since the recovery profile of mivacurium is independent of the dose and duration, it is most suitable for administration by continuous infusion. The infusion requirement in children is 10–16 μg·kg^?1 min^?1, which is about twice that of adults. Cutaneous flushes from histamine release are commonly seen with the larger doses of mivacurium; however, the associated hypotensive effects are minimal and counteracted by the tracheal intubation. The duration of action of mivacurium is prolonged in patients with cholinesterase deficiency. Mivacurium's neuromuscular effects can be satisfactorily antagonized by edrophonium or neostigmine.     

Pharmacokinetics of Controlled Release and Immediate Release Morphine Sulphate Tablets after a Single Dose and Multiple Doses in Chinese Volunteers

健康志愿者１０名，随机交叉口服硫酸吗啡控释片（ＣＲＭＳ）３０ｍｇ（３０ｍｇ×１）和硫酸吗啡普通片（ＩＲＭＳ）２０ｍｇ（１０ｍｇ×２），分别于服药前后各时点取静脉血，用ＧＣＭＳ测定血浆中吗啡含量。以药代软件程序处理，分别求得ＣＲＭＳ和ＩＲＭＳ的Ｃｍａｘ为１９．３８±３．８０和２１．２７±６．２１ｎｇ／ｍｌ；ｔｍａｘ为２．３６±０．３７ｈ和０．５５±０．１６ｈ；ｔ１／２β为３．５３±０．８７ｈ和３．０３±０．７４ｈ，曲线下面积ＡＵＣ为１４５．１５±１７．６５和９３．０８±１６．６５ｎｇ·ｈ／ｍｌ。癌症病人多次口服硫酸吗啡至稳态，ＣＲＭＳ和ＩＲＭＳ的峰浓度分别为２７．４３±０．３３ｎｇ／ｍｌ，２２．６８±０．１６ｎｇ／ｍｌ；谷浓度分别为１９．４５±１．４４ｎｇ／ｍｌ；１８．１４±０．４９ｎｇ／ｍｌ。     

Pharmacokinetics of intravenous and oral bolus doses of L-carnitine in healthy subjects

Summary The pharmacokinetics of single intravenous and oral doses of L-carnitine 2 g and 6 g has been investigated in 6 healthy subjects on a low carnitine diet.Carnitine was more rapidly eliminated from plasma after the higher dose. Comparing the 2-g and 6-g doses, the t_1/2 of the elimination phase () was 6.5 h vs 3.9 h, the elimination constant was 0.40 vs 0.50 h^–1 and the plasma carnitine clearance was 5.4 vs 6.11 × h^–1 (p<0.025), thus showing dose-related elimination.Saturable kinetics was not found in the range of doses given. The apparent volumes of distribution after the two doses were not significantly different and they were of the same order as the total body water. Urinary recoveries after the 2-g and 6-g doses were 70% and 82% during the first 24 h, respectively.Following the two oral dosing, there was no significant difference in AUCs of plasma carnitine. Urinary recoveries were 8% and 4% for the 2-g and 6-g doses during the first 24 h. The oral bioavailability of the 2-g dose was 16% and of the 6 h dose 5%. The results suggest that the mucosal absorption of carnitine is already saturated at the 2-g dose.     

不同剂量体外冲击波治疗肱骨外上髁炎的疗效对比

目的 比较不同能流密度的体外冲击波(extracorporeal shock wave, ESW)治疗肱骨外上髁炎(lateral epicondylitis, LE)的短期临床疗效,探索ESW的最佳治疗剂量。方法 将120例LE患者分为A、B、C和D 4组,均使用ESW治疗4周,各组的能流密度分别为0.06、0.08、0.10、0.12 mJ/mm²。分别在治疗前及治疗后4、24及48周,比较4组患者疼痛视觉模拟量表(visual analogue scale, VAS)评分、肱骨外上髁炎功能评估(patient-rated tennis elbow evaluation, PRTEE)评分及末次随访患者满意度和复发率。结果 按时间点比较,各组VAS评分治疗前最高,治疗后48周降至最低(P<0.05),4组患者满意度及复发率比较差异无统计学意义(P>0.05),但C组患者满意度(96.67%)明显高于A组(80%),差异具有统计学意义(P=0.04)。按组间比较观察,治疗前各组患肘VAS评分差异无统计学意义(P>0.05);治疗后4、24和48...     

Dual effects of melatonin on barbiturate-induced narcosis in rats

Melatonin affects the circadian sleep/wake cycle, but it is not clear whether it may influence drug-induced narcosis. Sodium thiopenthal was administered intraperitoneally into male rats pre-treated with melatonin (0.05, 0.5, 5 and 50 mg/kg). Melatonin pre-treatment affected in a dual manner barbiturate narcosis, however, no dose-effect correlation was found. In particular, low doses reduced the latency to and prolonged the duration of barbiturate narcosis. In contrast, the highest dose of melatonin (50 mg/kg) caused a paradoxical increase in the latency and produced a sustained reduction of the duration of narcosis, and a reduction in mortality rate. Melatonin 0.5 and 5 mg/kg influenced the duration but not the latency of ketamine- or diazepam-induced narcosis. Thus, the dual action of melatonin on pharmacological narcosis seems to be specific for the barbiturate mechanism of action.     

High-dose inhaled steroids in the management of asthma A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function

Svendsen UG, Frølund L, Heinig JH, Madsen F, Nielsen NH, Weeke B. High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function.
The efficacy of budesonide (800 μg b.d.) and beclomethasone dipropionate (750 μg b.d.) in controlling the symptoms of asthma, pulmonary function, bronchial responsiveness to histamine, and adrenal function, was assessed in a double-blind, double-dummy cross-over study of 36 adult chronic asthmatic patients. The patients, the majority of whom were assessed to be affected to a severe degree, were insufficiently controlled in their current regimen of inhaled steroids and/or inhaled and oral bronchodilators. A 2 weeks baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups showed improvements from baseline in clinical assessment of lung function carried out after the first 6 weeks of treatment. No significant differences were seen throughout the entire 12 weeks study, when comparing the effects of the treatments on FEV₁ FVC, PEF or the histamine PC₂₀. Asthma severity, symptom score and inhaled bronchodilator use showed the same results after both treatments. It is concluded that inhalations of budesonide and beclomethasone dipropionate in high doses are equally potent in the treatment of severe asthma. There is no significant influence on the adrenal function and no significant side effects during a period equal to that of the present study.     

Evaluating the impact of a service fee on patient compliance

This paper addresses an evaluation of an administrative decision to change the manner in which services were paid for at a Student Health Center (SHC). The impact of the change in payment was observed through monitoring the number of scheduled appointments at the SHC which the patient failed to attend, reschedule, or cancel. The impact was assessed through a comparison of the weekly no-show rates from the year prior to the change in payment practices through the year following the change. A time-series statistical package was used to analyze the no-show data. Collateral measures on the number of students attending the university, staff opinions, and usage of the SHC by different student groups were collected. Evaluations of the impact of administrative decisions on health-related behavior were discussed, in addition to a discussion of the usefulness of time-series models for this type of evaluation.     

Influence of food on the intravenous and oral dose kinetics of propranolol in the dog

The intravenous and oral dose kinetics of propranolol were studied in the dog both in a fasted state and immediately after a meal consisting of 100 g of cooked beef liver. Fifty Ci of³H-propranolol was administered intravenously simultaneously with a 40-mg oral dose of unlabeled propranolol. Plasma³H-propranolol was measured by specific extraction and liquid scintillation spectrometry, and unlabeled plasma propranolol was determined by gas chromatography-mass spectrometry. Feeding significantly reduced (25%) the elimination half-life and increased (52%) the systemic clearance of intravenous propranolol. The increase in the systemic clearance of propranolol after feeding was mostly due to an increase (60%) in apparent hepatic blood flow, which appeared to remain elevated for 5–7 hr. The meal had no influence on the apparent volume of distribution or plasma binding. Feeding did not affect the area under the concentration-time curve of oral propranolol, but significantly delayed the rate of oral propranolol absorption, shifting the time to reach peak plasma levels from 60 to 158 min. The results of this study suggest that feeding alters the disposition of propranolol in the dog by producing a sustained increase in hepatic blood flow.This work was supported by National Institute of Health grants GM 07534, GM 20387, and HL 29566.     

提高稀释液浓度测定硫酸卡那霉素含量

目的：探讨按中国药典（2000年版）抗生素微生物检定法测定硫酸卡那霉素含量的最后稀释液浓度范围；方法：应用ZY－300IV型抗生素抑菌圈面积测量分析仪，测定硫酸卡那霉素抑菌圈面积与对数剂量的线性关系范围；结果：测定硫酸卡那霉素含量时，最后稀释液浓度范围在5.5-20.4IU/ml内对数剂量与抑菌圈面积呈直线关系。