加替沙星对慢性阻塞性肺疾病患者茶碱缓释片体内清除率的影响

目的研究加替沙星对慢性阻塞性肺疾病(COPD)患者茶碱缓释片体内清除率的影响。方法通过对临床慢性COPD患者联用加替沙星前后茶碱血药浓度的测定,获得相关药动学参数并作统计处理。结果联用加替沙星前后茶碱血药浓度升高,清除率有显著降低。结论加替沙星明显延缓茶碱在体内的代谢,临床上二者联用时应监测茶碱的血药浓度,以保证安全。     

司帕沙星对老年慢性阻塞性肺病患者茶碱缓释片药动学的影响

目的:研究司帕沙星对老年慢性阻塞性肺病(COPD)患者茶碱缓释片药动学的影响.方法:采用荧光偏振免疫法检测18例老年COPD患者联用司帕沙星前后茶碱各时点的血药浓度,用PKBP-N1程序求得药动学参数,并作统计学分析.结果:联用司帕沙星(200mg,qd)5 d后血药浓度较联用前均有升高(P＜0.01),药动学参数曲线下面积(AUC)及最大峰浓度(Cmax)差异有极显著性(P＜0.01).结论:司帕沙星以200 mg,qd给药对茶碱的药动学有显著性影响,临床联用时应监测茶碱血药浓度,防止茶碱因代谢减慢而引起中毒.     

洛美沙星对老年慢性阻塞性肺疾病患者茶碱血药浓度与药动学的影响

目的观察洛美沙星对老年慢性阻塞性肺疾病(COPD)患者茶碱血药浓度及药动学的影响。方法采用荧光偏振免疫法检测18例老年COPD患者联用洛美沙星(400 mg，q 12 h)前后茶碱各时点的血药浓度，用PKBP N1程序求得药动学参数并作统计学比较。结果联用洛美沙星5 d后茶碱血药浓度较联用前稍有升高(P＞005)，药动学参数除达峰时间(tmax)缩短差异有显著性(P＜005)，其余变化均差异无显著性(P＞005)。结论洛美沙星以400 mg，q 12 h给药对茶碱的药动学无明显的影响。     

健康人体内甲磺酸加替沙星对茶碱稳态药代动力学的影响

目的:研究甲磺酸加替沙星对健康人体内茶碱稳态药代动力学的影响。方法:采用HPLC法测定健康人体单独给药和合并甲磺酸加替沙星给药后茶碱的血药浓度,采用3P97药动学软件处理,选用非参数法计算药动学参数,Cmax和Tmax为实测值,AUC采用梯形法计算曲线下积分面积。主要药动学参数采用SPSS11.5软件进行统计分析。结果:单用和合用甲磺酸加替沙星后,茶碱的药动学参数Cmax、t1/2、CL、AUC0-12、AUC0-∞之间有显著性差异(P<0.01)。Cmax明显下降,t1/2明显减小,AUC0-12与AUC0-∞明显下降。结论:甲磺酸加替沙星对健康人体内茶碱稳态药动学有影响,两者合用可能降低茶碱疗效,提示两药合用应监测茶碱的血药浓度。     

非洛地平对中老年慢性阻塞性肺病患者茶碱控释片药动学的影响

目的:观察钙通道拮抗剂非洛地平对茶碱血药浓度及药动学参数的影响。方法:采用荧光偏振免疫法检测8例中老年慢性阻塞性肺炎患者在联用非洛地平前后茶碱各时点的血药浓度,并用PKBP-N1程序求得药动学参数,用配对T检验法作统计学分析。结果:联用非洛地平后茶碱血药浓度比单用药时消除明显减慢,但只有在给药后8.0h一个时间点,合并用药比单用茶碱时茶碱血药浓度升高有显著性(P<0.05),而且从药动学参数来看,联用非洛地平对茶碱的消t1/2β、Ke、Vd差异有显著性。AUC、Cm ax、tm ax、Ka、t1/2α均差异无显著性(P>0.05)。结论:合用非洛地平和茶碱,非洛地平能延缓茶碱在慢阻肺患者体内的消除,茶碱的血药浓度则一直在正常治疗浓度范围,但需要密切监测茶碱的血药浓度。     

加替沙星对家兔茶碱药动学的影响

目的 :观察注射用加替沙星对茶碱在家兔体内药动学的影响。方法 :采用荧光偏振免疫分析法 (FPIA)测定氨茶碱单用及与加替沙星合用后家兔体内茶碱血清浓度 ,并对 2组药动学参数进行统计学处理。结果 :单用氨茶碱及与加替沙星合用后的药 -时曲线符合 -室模型。加替沙星使茶碱的AUC、血药浓度显著增加 (P均 <0 0 5 ) ;表观分布容积显著下降 (P <0 0 5 ) ;清除率显著下降 (P <0 0 1) ;消除半衰期相应延长 ,消除速率常数减少 ,但无统计学意义 (P >0 0 5 )。结论 :在家兔体内 ,合用加替沙星对茶碱的消除药动学有显著抑制作用     

非洛地平对茶碱控释片在慢性阻塞性肺疾病患者体内药动学的影响

目的观察非洛地平对茶碱控释片在慢性阻塞性肺疾病患者体内血药浓度与药动学的影响。方法采用高效液相色谱法测定合用非洛地平前后不同时间茶碱的血药浓度，采用3P87程序判别模型并计算参数。结果联用非洛地平后茶碱血药浓度比单用茶碱时消除明显减慢，但只有在给药后8.0 h合并用药比单用茶碱时茶碱血药浓度高，且差异有显著性（P＜0.05）。联用非洛地平对茶碱的消除半衰期(t1/2β)、消除速率常数(Ke)、表观分布容积（Vd）均有显著影响（均P＜0.05），AUC、Cmax、tmax、ka、t1/2α等无明显变化。结论联合使用非洛地平和茶碱时，非洛地平能延缓茶碱在慢性阻塞性肺疾病患者体内的消除，但茶碱的血药浓度能保持在正常治疗浓度范围。长期联用非洛地平和茶碱控释片需要密切监测茶碱的血药浓度。     

兔体内加替沙星对多索茶碱药动学的影响

目的研究兔体内加替沙星对多索茶碱药动学影响。方法16只大耳白兔按随机分为多索茶碱单用组和多索茶碱与加替沙星合用组,用高效液相色谱法(HPLC)分别测定多索茶碱的血药浓度,以3P97药动学软件对药-时数据进行处理,并进行统计分析。结果单用组和合用组多索茶碱的主要药动学参数分别为Cmax:(30.95±8.28)μg/ml,(31.25±6.23)μg/ml(P>0.05);t1/2β:(1.83±0.037)h,(1.89±0.042)h(P>0.05);AUC:(67.20±2.05)μg/ml,(69.20±2.58)μg/ml(P>0.05)。结论兔体内两药合用时加替沙星对多索茶碱的药动学无显著影响。     

加替沙星对老年慢性阻塞性肺病患者茶碱群体药代动力学的影响分析

目的探讨加替沙星对老年慢性阻塞性肺疾病患者茶碱群体药代动力学的影响。方法应用非线性混合效应模型(NONMEM)程序对所选16例老年慢性阻塞性肺疾病患者进行研究,分析前瞻性收集现口服茶碱缓释片、再联用加替沙星的16例老年慢性阻塞性肺疾病患者256份茶碱血药浓度样本。采用一级吸收一房室开放的模型进行实验患者的群体数据采集,估算所选患者的吸收速率常数(ka)、体内清除率(CL/F)、分布溶剂(V)及滞后时间(ALAG)的个体事件变异用指数模型,患者个体自身的变异数据采用加法模型进行计算。结果根据实验数据可知,单独服用茶碱缓释片与两种药物综合使用时,CL/F相比下降;了13.55%,其他数据无明显变化,两组数据对比差异具有统计学意义(P <0.05)。结论本研究针对老年慢性阻塞性肺疾病患者茶碱群体进行加替沙星结合治疗,可以有效提高药物在患者体内利用度,并保持药物在患者体内维持安全水平。     

司帕沙星及洛美沙星对老年慢性阻塞性肺病患者茶碱缓释片药动学的影响

目的　研究司帕沙星及洛美沙星对老年慢性阻塞性肺病(COPD)患者茶碱缓释片药动学的影响。方法　36例老年COPD患者口服茶碱缓释片10 0mg ,q8h×9d ,d 4起Ⅰ组18例合用司帕沙星片2 0 0mg ,qd ;Ⅱ组18例合用洛美沙星胶囊4 0 0mg ,q12h。于d 4、10采集血样,采用荧光偏振免疫法检测茶碱的血药浓度,用PKBP N1程序求得药动学参数。结果　合用司帕沙星后茶碱血药浓度较合用前明显升高(P <0 .0 1) ,AUC及cmax差异有高度统计学意义(P <0 .0 1) ;而合用洛美沙星后其血药浓度较合用前稍有升高(P >0 .0 5 ) ,药动学参数除tmax有统计学意义(P <0 .0 5 )外,其余的变化均无统计学意义。结论　司帕沙星对茶碱的药动学有显著性影响,而洛美沙星对茶碱的药动学情况基本上无明显的影响。     

左氟沙星对健康志愿者和慢性阻塞性肺病患者茶碱药物动力学的影响

目的:研究左氟沙星(LVFX)对人体茶碱药物动力学的影响.方法:应用均相酶免疫法.通过测定8名健康志愿者、6名慢性阻塞性肺病患者合用LVFX片前后po氨茶碱片的血药浓度,对合用LVFX前后茶碱药物动力学进行对比.结果:合用LVFX前后除患者组茶碱t_(max)有延长(P<0.01)外,两受试组的K、V_d/F、C_(max)、AUC(0-1)及健康志愿者组的t_(max)均无显著差异(P>0.05).结论:LVFX不影响人体茶碱的分布和清除,临床上可与氨茶碱安全合用.     

Kinetic interaction between theophylline and a newly developed anti-allergic drug,pemirolast potassium

The effect of a newly developed anti-allergic drug, pemirolast potassium (TBX), on the pharmacokinetics and metabolism of theophylline was investigated under steady-state conditions in seven healthy male volunteers. A sustained-release theophylline formulation (100 mg twice daily at 12 h intervals) was given as monotherapy and coadministered with TBX (10 mg twice daily at 12 h). Plasma concentration-time curves and the urinary excretion of theophylline and its major metabolites after administration of theophylline alone and after coadministration with TBX were compared.No significant adverse effects from this study were observed. There were no significant differences in the total body clearance, renal clearance and maximum concentration of theophylline between the two treatments, although coadministration of TBX significantly delayed the time to reach maximum concentration of theophylline. In the case of urinary excretion, no significant changes in the fraction of urinary excretion of theophylline and its metabolites were observed. These results indicate that TBX has little or no effect on the pharmacokinetics and metabolism of theophylline and suggest that TBX is safe for asthma patients receiving theophylline therapy for treatment of chronic obstructive airway diseases.     

茶碱在老年慢性阻塞性肺疾病患者中的群体药动学

目的：建立茶碱在老年慢性阻塞性肺疾病患者中的群体药动学（PPK）模型,并获取药动学参数,为临床制定个体化给药方案提供参考。方法：收集2014年4—12月某院诊断为慢性阻塞性肺疾病应用茶碱治疗的68例老年患者的血药浓度监测数据及临床资料,运用非线性混合效应模型法（NONMEN）定量分析性别、年龄、体质量及肝肾功能等因素对药动学参数的影响,最终建立PPK模型。采用拟合优度、自举法和可视化检验对最终模型的性能进行内部验证。结果：茶碱的药动学符合一室模型,最终模型公式为：CL=θ_CL×（WT/63）^θWT×exp（η_CL）,V=θ_V×exp（η_V）,其中的协变量为体质量,模型CL和V的群体典型值分别为0.849 L·h^-1,13.7 L。拟合优度、自举法和可视化检验的评价结果表明最终模型稳定,预测结果可靠。结论：建立的PPK模型能较好地描述茶碱在老年慢性阻塞性肺疾病患者中的药动学特点,患者体质量对参数CL有显著性影响。     

茶碱治疗慢性阻塞性肺病急性加重期的疗效

目的：观察茶碱在老年慢性阻塞性肺病（COPD）急性加重期的临床疗效,了解有效治疗的茶碱血药浓度.方法：选择老年COPD急性加重期患者60例,随机分为治疗组和对照组各30例,治疗组给予多索茶碱0.3 g,ivd,qd＋茶碱缓释片0.1g,po,bid＋地塞米松5 mg,ivd,qd;对照组给予特布他林0.5 mg雾化吸入q8h＋地塞米松5 mg,ivd,qd.治疗组于用药后2 d、5d、10 d清晨6时测定荼碱浓度.比较两组的患者住院时间、治疗费用、临床疗效、治疗前后肺功能、血气分析的变化及不良反应.结果：两组患者的肺功能和血气分析在治疗后均有明显改善（P＜0.01）,两组住院时间、治疗效果、实验室指标的改善无统计学差异（P＞0.05）,但治疗组的治疗费用低于对照组（P＜0.05）,不良反应的发生例数较对照组少,其中心血管系统不良反应的发生率有统计学意义.所有检测的茶碱血药浓度均小于20 μg·ml-1,其中仅8份标本血药浓度在10～20 μg·ml-1的治疗窗内.结论：茶碱在老年COPD急性加重期治疗中具有较好的临床应用价值,安全性高,值得推广.     

Dose-dependent kinetics of theophylline in adults with pulmonary diseases

The incidence of dose-dependent pharmacokinetics of theophylline was retrospectively investigated in adults with pulmonary disease receiving continuous aminophylline infusions. Twenty-one of 180 successive admissions to medical intensive care units with a diagnosis of chronic obstructive pulmonary disease, asthma, or respiratory failure met the criteria of two steady-state serum theophylline concentrations on two different doses. Of these, 14 patients continued to smoke, whereas 7 had never smoked or had stopped greater than 1 year prior to admission. No statistical difference existed between the mean systemic clearances of theophylline at the two different doses, using either total body weight or ideal body weight. Only 1 of the 21 patients met the criteria for dose dependency of a greater than or equal to 50% reduction in clearance with dosage increase. Six of eight subjects with decreased clearance on the higher dose were nonsmokers. In contrast, all nine with augmented clearance following dosage increase were smokers. Four were considered to have proportional changes. In general, nonsmoking patients tended to have greater changes in serum theophylline concentration than in dosage. Conversely, smoking patients demonstrated smaller changes in concentration. The relationship of smoking status and dose-dependent theophylline elimination is discussed.     

稳态时加替沙星对茶碱在家兔体内药动学的影响

目的 :研究稳态时加替沙星对茶碱在家兔体内药动学的影响。方法 :采用自身对照法 ,HPLC法平行监测合用药前后茶碱的血药浓度 ,通过PKBP N1软件拟合茶碱的药动学参数 ,并做统计学比较。结果 :合并用药前后茶碱的血药浓度AUC差异有显著性 (P <0 .0 5 ) ,合用后茶碱的血药浓度显著提高 ,峰时Tmax提前 ,吸收速率Ka 变大 ,消除半衰期T1 / 2 β相应延长 ,消除率相应减少。结论 :加替沙星能延缓茶碱在体内的代谢 ,提示合并用药时应对茶碱进行血药浓度监测 ,防止因茶碱代谢减慢而引起蓄积中毒。     

Influence of sulbactam plus ampicillin on theophylline clearance

The effect of sulbactam/ampicillin (500 mg/1000 mg) every 12 hours taken for seven days on the steady-state pharmacokinetics of theophylline was studied among 12 patients suffering from chronic obstructive pulmonary disease. Theophylline concentrations were measured serially for 12 h by the method of polarized immunofluorescence (Abbott TDx system). No influence of sulbactam/ampicillin was detectable on the theophylline half-life, clearance or volume of distribution. It was concluded that both drugs could be administered concomitantly without any dosage adjustment of theophylline.     

The effect of respiratory disorders on clinical pharmacokinetic variables

Respiratory disorders induce several pathophysiological changes involving gas exchange and acid-base balance, regional haemodynamics, and alterations of the alveolocapillary membrane. The consequences for the absorption, distribution and elimination of drugs are evaluated. Drug absorption after inhalation is not significantly impaired in patients. With drugs administered by this route, an average of 10% of the dose reaches the lungs. It is not completely clear whether changes in pulmonary endothelium in respiratory failure enhance lung absorption. The effects of changes in blood pH on plasma protein binding and volume of distribution are discussed, but relevant data are not available to explain the distribution changes observed in acutely ill patients. Lung diffusion of some antimicrobial agents is enhanced in patients with pulmonary infections. Decreased cardiac output and hepatic blood flow in patients under mechanical ventilation cause an increase in the plasma concentration of drugs with a high hepatic extraction ratio, such as lidocaine (lignocaine). On a theoretical basis, hypoxia should lead to decreased biotransformation of drugs with a low hepatic extraction ratio, but in vivo data with phenazone (antipyrine) or theophylline are conflicting. The effects of disease on the lung clearance of drugs are discussed but clinically relevant data are lacking. The pharmacokinetics of drugs in patients with asthma or chronic obstructive pulmonary disease are reviewed. Stable asthma and chronic obstructive pulmonary disease do not appear to affect the disposition of theophylline or beta 2-agonists such as salbutamol (albuterol) or terbutaline. Important variations in theophylline pharmacokinetics have been reported in critically ill patients, the causes of which are more likely to be linked to the poor condition of the patients than to a direct effect of hypoxia or hypercapnia. Little is known regarding the pharmacokinetics of cromoglycate, ipratropium, corticoids or antimicrobial agents in pulmonary disease. In patients under mechanical ventilation, the half-life of midazolam, a new benzodiazepine used as a sedative, has been found to be lengthened but the underlying mechanism is not well understood. Pulmonary absorption of pentamidine was found to be increased in patients under mechanical ventilation. Pharmacokinetic impairment does occur in patients with severe pulmonary disease but more work is needed to understand the exact mechanisms and to propose proper dosage regimens.