Relative efficacy of three different inhalers containing salbutamol in patients with asthma

Objective: To investigate the relative efficacy of three inhalers containing salbutamol: Turbuhaler (TBH), Rotahaler (RH) and Diskhaler (DH). Methods: A randomized, open, three-way crossover, cumulative dose response study was performed in 20 patients with asthma with mean forced expiratory volume in 1s (FEV₁) values of 60% of predicted (range 41–90%) and a 27% reversibility in FEV₁ (range 15–61%). Four doses of salbutamol were inhaled at 30-min intervals: 50 μg, 50 μg, 100 μg and 200 μg by TBH and 200 μg, 200 μg, 400 μg and 800 μg by both RH and DH. FEV₁ was measured at baseline and 25 min after each dose. Results: The increases in FEV₁ after the first doses (50 μg by TBH, 200 μg by RH and by DH) were not statistically significantly different (23.6%, 25.1% and 28%, respectively). Based on the parallel shift in the dose response curves, salbutamol TBH was calculated to be 2.4 times as potent as salbutamol RH (95% confidence interval 1.4–3.3) and 2.2 times as potent as salbutamol DH (90% CI 1.3–3.3). Additionally, during dosing with TBH, fewer patients experienced adverse events than during dosing with RH or DH. Conclusion: Turbuhaler is a twofold more efficient inhaler for salbutamol than Rotahaler or Diskhaler as measured by its bronchodilating effect. Received: 15 February 1996/Accepted in revised form: 16 February 1996     

Single dose and steady-state pharmacokinetics of 4 mg and 8 mg oral salbutamol controlled-release in patients with bronchial asthma

Summary Fifteen patients with asthma were given salbutamol controlled-release (SCR) 4 mg or 8 mg twice daily for seven days, in a randomised double-blind cross-over design. Plasma salbutamol levels were measured after the first and fifteenth doses for a 12 h period following drug ingestion.At steady-state the geometric mean values for C_max were 8.2 ng/ml for 4 mg, and 16.1 ng/ml for 8 mg. Median t_max values were 300 and 240 min respectively. The geometric mean AUC (0–12) were 4507 ng·min·ml^–1 and 8980 ng·min/ml. Peak to trough fluctuation ratios were 0.577 and 0.572.There were no significant differences between 4 mg or 8 mg formulations, for any of the parameters measured, after appropriate corrections for dose. The concentration-time profiles at steady-state showed little fluctuation in plasma salbutamol levels over the twelve hour dosing interval. These results show that 4 mg and 8 mg formulations of SCR provide smooth plasma profiles at steady-state with a twice daily dosing regime.Part of this paper has been presented in abstract form to the British Thoracic Society, Newcastle, July 1988     

沙丁胺醇联合布地奈德混悬液治疗小儿哮喘急性发作的效果观察

目的：探讨沙丁胺醇联合布地奈德混悬液治疗小儿哮喘急性发作的临床效果。方法将符合标准的116例哮喘急性发作患儿随机分成观察组和对照组,各58例,对照组采用常规方法治疗,观察组采用沙丁胺醇联合布地奈德混悬液治疗。结果治疗后,观察组肺部哮鸣音消失率为65.5%,高于对照组的46.6%（P<0.05）;观察组临床控制率与总有效率均高于对照组（P<0.05）。观察组咳嗽、喘憋、气促、肺部啰音消失时间均短于对照组（P<0.05）。结论沙丁胺醇联合布地奈德混悬液治疗小儿哮喘急性发作安全有效,副作用小,不易产生耐药性,值得临床推广应用。     

Efficacy and safety of single therapeutic and supratherapeutic doses of indacaterol versus salmeterol and salbutamol in patients with asthma

ABSTRACT

Objective: This study compared the bronchodilator efficacy and safety of indacaterol with placebo, salbutamol and salmeterol, in patients with persistent asthma, at single therapeutic and supratherapeutic doses.

Research design and methods: This was a randomised, open-label crossover study in adult subjects with asthma (forced expiratory volume in 1 second [FEV₁] ≥?60% predicted). In part A, patients (n = 20) received single doses of indacaterol 200?µg, salbutamol 200?µg, salmeterol 50?µg and placebo. In part B, patients (n = 19) received single doses of indacaterol 1000?µg, salbutamol 1000?µg, salmeterol 250?µg and placebo.

Main outcomes measures; Results: For the primary endpoint, FEV₁ area under the effect curve during 0–24?h, indacaterol 200?µg was statistically superior to placebo and salbutamol. Indacaterol 200?µg FEV₁ was higher than placebo (5?min to 24?h), salbutamol 200?µg (4–24?h), and salmeterol 50?µg (5 and 15?min and 22 and 24?h). Few adverse events were reported; all were mild or moderate in severity. Initial changes were observed in glucose, potassium, heart rate and QTc interval, but all values remained within normal ranges. Values matched placebo levels after a shorter time for indacaterol 1000?µg than for salmeterol 250?µg.

Conclusions: In this single-dose, open-label study, indacaterol 200?µg provided effective 24‐h bronchodilation, with a longer duration than salmeterol 50?µg and a good overall safety profile. The sustained bronchodilation of indacaterol 1000?µg was not associated with sustained systemic adverse effects.     

Subsensitivity of beta-adrenoceptor responses in asthmatic patients taking regular low dose inhaled salbutamol

Summary Tremor (Tr), chronotropic (HR) and metabolic (K, Glu) responses to cumulative doses of inhaled salbutamol (100 g to 4000 g) were compared in an age and sex matched group of 7 normal (N) and asthmatic (A) subjects.Comparison of regression lines between groups showed differences in HR and K. This was also reflected in attenuation of maximum responses in group A, for HR and K.These results show subsensitivity of chronotropic and hypokalaemic responses in patients with asthma, which may reflect tachyphylaxis from the effects of long term inhaled salbutamol therapy.     

Pharmacokinetics,efficacy and adverse effects of sublingual salbutamol in Patients with asthma

Summary Administration of drugs by the sublingual route provides rapid systemic absorption and avoids first-pass metabolism. The purpose of the present study was to assess the pharmacokinetics, efficacy and adverse effects of standard salbutamol tablets given by this route to patients with asthma. Seven asthmatic patients were given either sublingual salbutamol tablet 2 mg (SL), swallowed tablet 2 mg (O), metered dose inhaler 200 µg (MDI) or placebo (PL), in a randomized single-blind cross-over design. Airways responses (FEV₁, FVC, PEFR), finger tremor (Tr), heart rate (HR), plasma potassium (K) and plasma salbutamol were measured over a 6 h period following drug administration.There were highly significant changes in FEV₁ with MDI, O and SL routes compared with PL, although the response to MDI was greater and more rapid than with O or SL. There were similar findings for FVC and PEFR responses. There were no adverse effects with MDI, whereas both 0 and SL produced significant tremor responses. There were no differences between O and SL for any of the pharmacodynamic parameters. In addition, pharmacokinetic profiles for O and SL were also similar apart from an initial delay in absorption with SL. There were however, no significant differences in any of the pharmacokinetic parameters, between O and SL.This suggests that buccal absorption of salbutamol was negligible, and that systemic absorption occurred after swallowing of the dissolved sublingual tablet. These results show that sublingual administration of salbutamol tablet has no clinical benefit over the oral route.     

Pharmacokinetics of controlled-release verapamil in healthy volunteers and patients with hypertension or angina

AIMS: To study the dose-ranging population pharmacokinetics of controlled release verapamil in healthy subjects and patients with angina or hypertension. To characterize the pharmacodynamics of controlled-release verapamil in patients with hypertension. METHODS: Dose-ranging studies were conducted in healthy volunteers and patients with hypertension and angina. Subjects received doses of 120, 180, 360, or 540 mg racemic verapamil as an osmotic controlled-release formulation. A population pharmacokinetic model involving zero-order release of verapamil into the gastrointestinal tract with first-order absorption and elimination was used to describe the steady-state plasma concentration profile for R- and S-verapamil. A population sigmoid E(max) pharmacodynamic model was used to describe the effect of R- and S-verapamil on mean arterial blood pressure. RESULTS: S-verapamil had an approximate 4-fold greater apparent clearance than R-verapamil in both healthy volunteers and patients. The apparent plasma clearance of R- and S-verapamil in healthy volunteers decreased over the dose range of 120-540 mg. A similar dose-dependent decrease in apparent plasma clearance was also noted in patients. None of the patient demographic variables examined (age, total body weight, lean body weight, body mass index, and height) explained the variability in verapamil pharmacokinetics. The pharmacodynamic model describing the relationship between verapamil plasma concentration and mean arterial blood pressure indicated that the S-verapamil had a 3.6-fold lower estimated EC(50) compared to R-verapamil. CONCLUSIONS: The results from this dose-ranging pharmacokinetic investigation in healthy volunteers and patients are consistent with previous reports in healthy subjects. S-verapamil is cleared more rapidly than R-verapamil and the estimated EC(50) for S-verapamil was 3.6-fold lower than for R-verapamil. Estimated EC(50) values for R- and S-verapamil decreased with increasing age and decreasing weight.     

Comparison of the efficacy,tolerability and patient acceptability of once-daily bambuterol tablets against twice-daily controlled release salbutamol in nocturnal asthma

The aim of the study was to compare the efficacy, tolerability and patient acceptability of bambuterol (Bambec^®) against controlled release (CR) salbutamol (Volmax^®) in the treatment of nocturnal asthma.One hundred and fifty two asthmatic patients aged 17–78 years, using 800 g/day of an inhaled steroid, with nocturnal asthma symptoms, openly received three weeks of bambuterol 20 mg nocte and three weeks of salbutamol CR 8 mg b.i.d. in a randomised, cross over sequence.Both bambuterol and salbutamol CR treatment produced a significant 63% decrease in the severity of baseline nocturnal asthma symptoms. This improved control of nocturnal asthma was reflected by significant improvements in baseline lung function. Both the severity and number of days of tremor during the first week of treatment was significantly lower with bambuterol than with salbutamol CR. Patients considered bambuterol to cause less shakiness and treatment preference was bambuterol 49%, salbutamol CR 36%, no preference 15%. The predominant reason for patient treatment preference was control of asthma symptoms, however a significant sub-group of patients (27%) chose bambuterol because of fewer adverse effects compared to 11% chosing salbutamol CR. Fifty six percent of patients preferred taking their medication once-daily and 7% preferred twice-daily.This study shows that both bambuterol and salbutamol CR are equally effective treatments for nocturnal asthma in patients already receiving inhaled steroid. The most important factor in terms of patient treatment acceptability appears to be control of symptoms. Sub-groups of patients may chose bambuterol due to its better adverse effect profile and once-daily regimen.     

沙丁胺醇联合布地奈德对咳嗽变异性哮喘的治疗

目的观察沙丁胺醇联合布地奈德对咳嗽变异性哮喘疗效。方法纳入CVA患儿64例为观察对象,随机分为观察组和对照组各32例。两组均给予布地奈德气雾剂吸入,布地奈德2～7岁：200μg,2次/d;7岁以上：400μg,2次/d。咳嗽停止后续用至疗程满3个月改为200μg1次/d,维持3个月。同时,观察组给予沙丁胺醇气雾剂,每次1喷,3次/d。咳嗽消失后停药;对照组口服氯雷他定,体重＆gt;30kg：10mg,1次/d。体重≤30kg：5mg,1次/d。两组计入观察的疗程均为前3个月,峰流速仪测量最高呼气流速。结果①两组患者咳嗽消失率均为100%,观察组咳嗽消失时间为平均（9.75±4.90）d,对照组（13.83±6.19）d,两组比较有显著性差异（P〈0.05）;②治疗后两组PEF值均有显著增加（P〈0.05）,观察组晨、晚间PEF与观察组比较差异无显著性（P〈0.05）。结论吸入型速效β2受体激动剂可快速有效缓解CVA患者咳嗽症状。     

Evaluation of plasma and urinary salbutamol levels in COPD

Objective: To evaluate the use of trough plasma salbutamol and overnight urinary salbutamol excretion in the assessment of nebulised salbutamol delivery in patients with chronic obstructive pulmonary disease (COPD). Methods: Twenty in-patients with COPD receiving nebulised salbutamol, age 69.7 years, FEV₁ 38.1% predicted, were studied on two consecutive days, receiving four 2.5 mg doses of nebulised salbutamol on day 1 and four 5 mg doses of nebulised salbutamol on day 2, the first dose at 8.00 h the last dose at 22.00 h. Salbutamol delivery was assessed after the last dose by trough plasma salbutamol 8.00 h and overnight urinary excretion of salbutamol (22.00–8.00 h). Results: Levels of urinary salbutamol were detectable in all 20 patients at both doses, whereas for plasma salbutamol detectable levels were only found in 16/20 cases at the 2.5 mg dose and in all cases at the 5 mg dose. For overnight urinary salbutamol (μg⋅10 h⁻¹  n = 20) the results were 141 for 2.5 mg and 249 for 5 mg. The dose ratio for urinary salbutamol between 2.5 mg and 5 mg doses was 1.83. Results for plasma salbutamol (ng/ml, n = 16) were 1.58 at 2.5 mg and 2.43 at 5 mg: dose ratio (geometric mean) 1.49. Conclusion: Overnight urinary salbutamol provides a simple and effective measure of nebulised salbutamol delivery in patients with COPD, which would be suitable for studying nebuliser performance and compliance. Received: 14 March 1996/Accepted in revised form: 14 May 1996     

Comparison between oral procaterol and salbutamol in patients with bronchial asthma

The efficacy of procaterol, a new beta 2-selective sympathomimetic drug, was compared with that of salbutamol and placebo in a double-dummy crossover study in 20 asthmatic patients. Procaterol (0.1 mg orally) was given twice daily and salbutamol (4 mg orally) 3-times a day. The study was made up of four consecutive 4-day treatment periods including two periods of plain placebo. A significant direct bronchodilating effect of both procaterol and salbutamol could be seen in PEF values, measured 4-times a day, compared with the effect of placebo (p less than 0.01 for both). Procaterol was slightly superior to salbutamol. The afternoon and evening PEF values during the procaterol period did not differ from the values during the placebo period. In symptom scores, there was significantly more tremor during the procaterol period than during the placebo period (p less than 0.01). Both procaterol and salbutamol produced more palpitation than placebo (p less than 0.05). The study shows that oral procaterol is a potent bronchodilator. The doses of procaterol and salbutamol were not equivalent. Procaterol with the dose used in the study was more potent. Despite this, the duration of the bronchodilator effect of procaterol on a twice daily dosage did not seem to be long enough in all patients.     

Pharmacokinetics of oral betaine in healthy subjects and patients with homocystinuria

AIMS: Large oral doses of betaine have proved effective in lowering plasma homocysteine in severe hyperhomocysteinaemia. The pharmacokinetic characteristics and metabolism of betaine in humans have not been assessed and drug monitoring for betaine therapy is not available. We studied the pharmacokinetics of betaine and its metabolite dimethylglycine (DMG) in healthy subjects and in three patients with homocystinuria. METHODS: Twelve male volunteers underwent an open-label study. After one single administration of 50 mg betaine kg-1 body weight and during continuous intake of twice daily 50 mg kg-1 body weight, serial blood samples and 24 h urines were collected to determine betaine and DMG plasma concentrations and urinary excretion, respectively. Patients were evaluated after one single dose of betaine. RESULTS: We found rapid absorption (t(1/2),abs 00.28 h, s.d. 0.17) and distribution (t(1/2), lambda1 00.59 h, s.d. 0.22) of betaine. A Cmax of 0.94 mmol l-1 (s.d. 0.19) was reached after tmax 00.90 h (s.d. 0.33). The elimination half life t(1/2), z was 14.38 h (s.d. 7.17). After repeated dosage, t(1/2), lambda1 (01.77 h, s.d. 0.75) and t(1/2), z (41.17 h, s.d. 13.50) increased significantly (95% CI 0.73, 01.64 h and 19.90, 33.70 h, respectively), whereas absorption remained unchanged. DMG concentrations increased significantly after betaine administration and accumulation occurred to the same extent as with betaine. Renal clearance was low and urinary excretion of betaine was equivalent to 4% of the ingested dose. Distribution and elimination kinetics in homocystinuric patients appeared to be accelerated. CONCLUSIONS: Betaine plasma concentrations change rapidly after ingestion. Elimination half-life increased during continuous dosing over 5 days. Betaine is mainly eliminated by metabolism. More pharmacokinetic and pharmacodynamic studies in hyperhomocysteinaemic patients are needed to refine the current treatment with betaine.     

硝苯地平控释胶囊在Beagle犬体内的药动学研究

目的评价自制硝苯地平(NF)控释胶囊在Beagle犬体内的药动学,并对其体内外相关性进行研究。方法 6只健康Beagle犬随机分成2组,分别单剂量服用实验制剂(硝苯地平控释胶囊)和参比制剂(拜新同渗透泵片)各30 mg,一周后交叉给药。采用HPLC法,以尼群地平(NT)为内标测定犬给药后不同时间的血药浓度,用以估算药动学参数和相对生物利用度。结果实验制剂与参比制剂的主要药动学参数分别为:Cmax(21.79±8.11)、(21.99±3.97)ng·mL-1;tmax(8.32±1.51)、(9.31±1.02)h;AUC0^t(337.42±84.44)、(348.65±56.25)ng·h·mL-1;t1/2(9.27±1.75)、(8.96±1.73)h;相对生物利用度为(96.8±7.34)%;体内外相关性r=0.944。结论自制硝苯地平控释胶囊具有明显的控释特性,体内外相关性良好。     

布地奈德联合沙丁胺醇雾化吸入治疗小儿支气管哮喘的临床效果观察

目的探讨布地奈德联合沙丁胺醇雾化吸入治疗小儿支气管哮喘的临床效果。方法将84例支气管哮喘的患儿随机分为治疗组与对照组,每组各42例。治疗组给予布地奈德联合沙丁胺醇雾化吸入进行治疗,对照组给予单纯的沙丁胺醇雾化吸人进行治疗,比较两组的临床疗效。结果治疗组的总有效率为83．33％,明显高于对照组的52．38％（P〈0．05）。结论布地奈德联合沙丁胺醇雾化吸人治疗小儿支气管哮喘疗效确切,不良反应少,值得临床推广应用。     

异丙托溴铵联合沙丁胺醇治疗小儿哮喘的效果观察

目的 观察异丙托溴铵联合沙丁胺醇治疗小儿哮喘的效果.方法 随机选取本院收治的5～14岁哮喘患儿156例,将其随机分成两组,其中,对照组80例采用基础治疗和雾化吸入沙丁胺醇治疗,其余76例患儿在上述治疗的基础上联合使用异丙托溴铵进行雾化治疗,并标记为观察组.0.5％沙丁胺醇以微量气泵的方式吸入,每次吸入量为0.02 ml/kg,观察组患儿同时将0.025％的异丙托溴铵溶液0.5 ml与0.9％的氯化钠溶液混合,并以微型气泵吸入,5 ml/次,2次/d,比较两组治疗效果.结果 观察组患儿的显效率为31.6％ （24/76）,明显高于对照组的12.5％ （10/80） （P＜0.05）;观察组的总有效率为89.5％（64/76）,明显高于对照组的70.0％ （56/80）（P＜0.05）;治疗后观察组患儿肺功能明显改善,哮喘发作频率降低,日间、夜间评分情况优于对照组（P＜0.05）.结论 联合应用沙丁胺醇和异丙托溴铵能明显降低小儿哮喘的发作频率,提升患儿的生活质量.     

Bronchoprotective and bronchodilator effects of single doses of (S)-salbutamol, (R)-salbutamol and racemic salbutamol in patients with bronchial asthma

Objectives: The drug salbutamol is used as a 50: 50 racemic mixture of its two enantiomers, (R)- and (S)-salbutamol. Previous studies suggest that the (R)-enantiomer is active, and the (S)-enantiomer is either inert or may be responsible for adverse effects. The aim of the study was to measure the protection given against methacholine (MCh) and adenosine monophosphate (AMP) by (R)-, (S)- and rac-salbutamol and their bronchodilator effects. Methods: A double-blind, placebo-controlled, four-way cross-over study was performed in subjects with mild to moderate asthma. There were three groups: AMP₃₀ (n = 10), MCh₃₀ (n = 13) and MCh₁₈₀ (n = 10). The groups received AMP or MCh challenges at either 30 min or 180 min after each of four pretreatments: 100 μg (S)-salbutamol, 100 μg (R)- salbutamol, 200 μg rac-salbutamol or placebo (normal saline), each administered via nebuliser. Spirometry was measured at 30, 60, 90, 120, 150 and 180 min in the MCh₁₈₀ group. Results: (R)- and rac-salbutamol showed equivalent bronchoprotective effects at 30 min. PC₂₀AMP increased by 3.22 (1.86) and 3.41 (2.15) doubling doses (P < 0.001) and PC₂₀MCh increased by 2.86 (1.09) and 2.75 (0.89) (P < 0.001) respectively. (S)-salbutamol caused no equivalent effect. There was no significant effect at 180 min. No hyper-responsiveness occurred after treatment with (S)-salbutamol. The mean increase in forced expiratory volume in 1 s (FEV₁) was 12.4% (6.8%) with (R)- and 12.0% (7.7%) with rac-salbutamol at 90 min. No significant change in FEV₁ occurred with (S)-salbutamol. Conclusions: These results confirm other recent findings that the bronchoprotective and bronchodilator effects of salbutamol are attributable to its (R)-enantiomer. No adverse effects were noted after single doses of (S)-salbutamol. Received: 23 September 1998 / Accepted in revised form: 12 February 1999     

硫酸沙丁胺醇口腔崩解片的制备及质量评价

目的：优选硫酸沙丁胺醇口崩片直压工艺,并测定其含量。方法：采用因子设计优选口崩片直压工艺,以直压甘露醇（pearlitol 200 DC）（X1）、交联聚维酮（PVPP）（X2）、微粉硅胶（silicon dioxide）（X3）、硬脂酸镁（MS）（X4）为自变量,以直压粉末的休止角（angle of repose）（Y1）、片子硬度（Hardness）（Y2）以及崩解时限（Disintegration）（Y3）为变量建立方程,最终确定直压工艺;采用反相高效液相色谱法测定样品含量。结果：X1、X3显著影响Y1,方程为Y1=35．8375—0．03125X1＋0．4X3-0．0425X1X3;X4显著影响Y2,方程为Y2=5．73875—0．54125X4;X2、X4显著影响Y3,方程为Y3=75—1．975X2＋20．375X4,通过等值线确定最佳处方,并且最佳处方的理论预测值在真实值波动范围内;硫酸沙丁胺醇在4～200ug／ml范围内线性良好,回收率为99．6％,RSD值为0．62％（n=9）。结论：硫酸沙丁胺醇直压工艺简便可行,建立的反相高效液相色谱法可用于硫酸沙丁胺醇口崩片的含量测定。     

吸入布地奈德／福莫特罗和布地奈德／沙丁胺醇对哮喘急性发作儿童支气管扩张的效果探讨

目的比较吸入布地奈德（100μg）／福莫特罗（6μg）、布地奈德（100μg）／沙丁胺醇（100μg）组合在5—15岁儿童哮喘发作期对支气管扩张的效果。方法采用双盲随机对照试验,研究组给予使用布地奈德100μg＋福莫特罗6μg组合压力式定量气雾装置吸入（MDI）,对照组给予布地奈德100μg＋沙丁胺醇100μg组合MDI。所有的儿童接受三次剂量的药物,给药间隔时间在20分钟以内。分析比较FEV1（％预计值）以及修正的肺指标值（MPIS）,研究两组在1、5、15、30、60分钟后的药效。结果干预后两组之间1、5、15、30、60分钟FEV1（％预计值）的比较差异无统计学意义（P〉0．05）。而对照组、研究组自身的（FEV1％预计值）绝对变化值,从基线到60分钟的差值为（12．2±2．5）以及（9．4±2．0）,两组比较差异有统计学意义（t=3．50,P〈0．05）。在两组基线相比,1、5、15、30、50分钟,从基线FEV1百分比变化也相似。呼气峰流速（PEFR）,百分比预测PEFR,用力呼气流速50（FEF50）和百分比预测FEF50,在两组相似研究过程中不同时间点也相似。其他肺功能参数两组之间比较差异无统计学意义。结论沙丁胺醇或福莫特罗,在二定吸入剂量的作用下,对轻度哮喘急性发作期5～15岁之间的儿童,有类似的支气管扩张作用。     

扎鲁司特联合沙丁胺醇治疗儿童支气管哮喘的临床研究

目的 观察扎鲁司特联合沙丁胺醇治疗儿童支气管哮喘的临床疗效。方法 选取2013年4月—2014年10月中国海洋石油南海西部医院收治的支气管哮喘患儿105例,随机分为对照组(51例)和治疗组(54例)。对照组将0.5 mL吸入用硫酸沙丁胺醇溶液用生理盐水稀释至2.5 mL,氧气驱动雾化吸入,氧流量为6～8 L/min,吸入时间为3～5 min/次,3次/d。治疗组在对照组的基础上口服扎鲁司特片,1片/次,2次/d。两组均连续治疗15 d。观察两组的临床疗效,同时比较两组患儿治疗前后的外周血肿瘤坏死因子(TNF-α)、白介素6(IL-6)、免疫球蛋白E(IgE)、一秒用力呼气容积(FEV₁)/用力肺活量(FVC)、呼气峰流量(PEF)的变化。结果 治疗后,对照组和治疗组的总有效率分别为72.55%、92.59%,两组比较差异有统计学意义(P <0.05)。治疗后,两组患儿TNF-α、IL-6、IgE水平均较治疗前显著降低,FEV₁/FVC、PEF显著升高,同组治疗前后差异有统计学意义(P <0.05);且治疗组这些观察指标的改善程度优于对照组,两组比较差异具有统计学意义(P <0.05)。结论 扎鲁司特联合沙丁胺醇治疗儿童支气管哮喘具有较好的临床疗效,可抑制炎症因子的表达,改善患儿肺功能,具有一定的临床推广应用价值。     

Pharmacokinetics of budesonide in children with asthma

Summary The pharmacokinetics of the glucocorticoid budesonide was studied in 6 children with asthma after i.v. injection of 0.5 mg and oral inhalation of 1 mg as an aerosol. Budesonide is a 1:1 mixture of the epimers 22 S and 22 R, which were assayed separately by HPLC combined with RIA. All pharmacokinetic parameters of the epimers differed except the half-life of about 1.5 h. It was significantly shorter than that reported in adults. Plasma clearance averaged 103 l · h^–1 for epimer 22 R and 74 l · h^–1 for epimer 22 S; calculated per kg body weight these values were about 50% higher than in adults. The difference was about 40% when calculated per m² of body surface area. Since budesonide is a high-clearance drug, the data indicate higher liver blood flow · kg^–1 body weight and m² of body surface area in children. The systemic availability of the aerosol was approximately 30% of nominal dose, i.e. the same as in adults. The high clearance and short half-life of budesonide in children are advantageous in reducing the risk of possible systemic side-effects of prophylactic treatment of asthma in childhood.