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。     

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。     

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。     

加替沙星对慢性阻塞性肺病患者茶碱缓释片药动学的影响

目的:研究加替沙星对慢性阻塞性肺病患者茶碱缓释片药动学影响。方法:慢性阻塞性肺病患者联用加替沙星前后采集血样,测定茶碱血浓度,拟合药动学参数。结果:联用加替沙星后,茶碱峰浓度、曲线下面积明显上升(P<0.01)。结论:加替沙星对茶碱药动学有显著性影响,临床上两者联用时应监测茶碱的血药浓度,以确保安全。     

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。     

葛根素注射液对多索茶碱在大鼠体内药动学的影响

目的研究葛根素对多索茶碱在大鼠体内药动学的影响。方法采用高效液相色谱（HPLC）法测定12只大鼠单独给药和联合葛根素给药后多索茶碱及其代谢产物茶碱的血浆浓度,采用DAS药动学软件对多索茶碱血浆浓度 时间数据进行非房室模型分析,求多索茶碱在大鼠体内的主要药动学参数,并进行统计分析。结果两组大鼠多索茶碱t1/2差异有统计学意义（P＜0.05）,合并用药组较单独用药组增加了6.65%;CL/F差异有统计学意义（P＜0.05）,合并用药组较单独用药组减少38.00%。单独给药组和合并给药组茶碱AUC（0 8）、Cmax、tmax差异无统计学意义（P＞0.05）,t1/2差异有统计学意义（P＜0.05）,合并用药组较单独用药组增加了35.29%;CL/F差异有统计学意义（P＜0.05）,合并用药组较单独用药组减少了35.29%。结论葛根素能抑制多索茶碱在大鼠体内代谢,且能延长多索茶碱代谢产物茶碱在体内的消除,两药同时使用应注意监测血茶碱浓度。     

氨溴索注射剂对多索茶碱在大鼠体内药动学的影响

目的研究氨溴索对多索茶碱（DP）在大鼠体内的药动学参数的影响。方法采用HPLE法测定16只大鼠单独给予DP和合并盐酸氨溴索给药后DP以及其代谢产物茶碱（TP）的血药浓度,用DAS药动学软件对DP血药浓度-时间数据采用非房室模型分析,求得DP在大鼠体内主要的药动学参数,并对其进行统计分析。结果2组大鼠DP药动学参数t1/2、AUC0→1、MRT0→7h、Vz/F、CL／F、tmax、ρmax差异均无统计学意义（P〉0．05）。但氨溴索与DP合并使用时,DP代谢产物TP的AUC0-7h2组差异具有统计学意义（P〈0．05）,合用组提高了38．77％。结论氨溴索对DP在大鼠体内动力学过程无影响,但有减缓DP的代谢产物TP代谢的趋势,两药同时使用时,应注意监测TP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。     

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.     

甲氟哌酸对茶碱在家兔体内药物动力学的影响

目的：在家兔体内观察甲氟哌酸对茶碱的药物动力学的影响。方法：动物分为２组，第１组静注茶碱１２ｍｇ·ｋｇ－１，第２组静注茶碱１２ｍｇ·ｋｇ－１和甲氟哌酸２０ｍｇ·ｋｇ－１，用高效液相法测定茶碱的血药浓度，计算机拟合房室模型并计算药物动力学参数。结果：茶碱的药时曲线符合二室模型，合用甲氟哌酸后，茶碱的药时曲线消除相血药浓度显著高于单用茶碱；茶碱的消除半衰期Ｔ１／２β和曲线下面积ＡＵＣ明显增大；机体清除率ＣＬ明显降低，两组之间有显著性或非常显著性差异。结论：甲氟哌酸能延缓茶碱在兔体内的清除，提示合并用药时应对茶碱进行临床给药监测。     

Inhibition of theophylline elimination in rabbits by verapamil

Single intravenous dose pharmacokinetics of theophylline in 10 rabbits were investigated before and after 5 days oral administration of verapamil in daily doses of 6 mg/kg. Verapamil caused a significant inhibition of theophylline elimination. Theophylline clearance was reduced from 126 to 98 ml/hr/kg (22.2%) whereas the steady state volume of distribution of the drug increased from 461 to 550 ml/kg (19.3%). The terminal half-life of theophylline increased from 2.7 to 4.0 hr (49.8%).     

酮替芬、西咪替丁及红霉素对茶硷药动学影响的实验研究

研究酮替芬、西咪替丁及红霉素对家兔体内茶碱代谢的影响,结果表明:酮替芬可加快茶碱代谢,使茶碱的血清半衰期t1/2由2.74±0.75h缩短至2.33±0.56h,缩短14.96%;消除速率常数Ke由0.27±0.075/h增至0.32±0.066/h,增加20%.清除率由0.15±0.036增至0.18±0.047L/kg·h~(-1)。西咪替丁可抑制茶碱的代谢,使茶碱t1/2由2.06±0.33h延长至2.61±0.45h,延长26.69%,Ke由0.34±0.04/h减小至0.27±0.04/h下降20.59％,Cl由0.21±0.03降低至0.16±0.03L/kg·h~(-1),下降23.81%。红霉素亦可减慢茶碱代谢速率,使茶碱的t1/2由2.39±0.43h延长至3.54±0.89h,延长48.12%;Ke由0.30±0.06/h减小至0.21±0.07/h.降低30%,Cl由0.15±0.03下降至0.12±0.03L/kg·h~(-1),降低20%。     

加替沙星滴眼液在兔眼房水中的药动学

目的探讨加替沙星滴眼液单次滴兔眼后在房水中的药动学特征。方法24只新西兰家兔,局部滴入加替沙星滴眼液50μL,以高效液相色谱法测定兔眼房水中加替沙星的药物浓度,用DAS1.0软件计算药动学参数。结果给药后0.5～6 h,加替沙星在兔眼房水中的c_(max)为(0.31±s 0.06)mg·L~(-1),消除半衰期为(3.4±0.7)h,AUC_(0～6h)为(0.70±0.22)mg·h·L~(-1),AUC_(0～∞)为(0.7±0.3)mg·h·L~(-1)。空白房水不干扰加替沙星的含量测定。结论加替沙星滴眼液单次滴兔眼后在眼房水中具有良好的药动学特征和组织通诱性。     

Comparative Pharmacokinetics of Theophylline in Rabbits and in Humans with Hyperlipidemia

The study was carried out on male rabbits divided into two groups: a control and an experimental one, fed on a high-fat diet. Humans were also ascribed into two groups: control and those affected with primary, mixed form of hyperlipidemia. The animals and humans were given theophylline intravenously as a single dose. Blood was sampled after 5, 10, 15, 30 and 45 min and 1, 2, 4, 6, 8, 12 and 24 h following theophylline administration. FPIA method was used to determine blood serum concentrations of theophylline. Considerable alterations of theophylline pharmacokinetics in humans suffering from mixed form of hyperlipidemia were observed. Marked decrease in area under the concentration–time curve (AUC), diminished volume of distribution, increased total body clearance, and shortened elimination half-life were observed. On the contrary, in rabbits with alimentary induced lipid metabolism disturbancest_1/2of theophylline was practically unchanged and AUC only slightly increased. In conclusion: (1) hyperlipidemia affects the pharmacokinetics of theophylline in human beings, (2) rabbit model with dietetary induced lipid metabolic disturbances is not a suitable subject for estimation of pharmacokinetics of xanthine derivatives.     

The effects of atropine on pharmacokinetics of theophylline in rabbits.

The effects of atropine on serum concentrations and pharmacokinetics of theophylline were studied in six rabbits (2.07 +/- 0.11 kg). Theophylline serum concentration was determined by ultraviolet spectrophotometry. After i.v. administration of aminophylline 12.5 mg/kg, i.m. atropine 1 mg/kg decreased significantly the maximal serum concentration of theophylline from 23.6 +/- 1.1 to 19.6 +/- 1.1 mg/l, and increased that of theophylline at the time of 6 and 8 hours after injection. After i.v. aminophylline administration without or with atropine, the pharmacokinetic parameters of theophylline calculated using a one compartment open model were: K (elimination rate constant) = 0.23 +/- 0.03, 0.19 +/- 0.02/h; t1/2 (half life) = 3.04 +/- 0.40, 3.66 +/- 0.40 h; Cl (clearance) = 0.26 +/- 0.04, 0.23 +/- 0.03 l/kg/h, respectively (P less than 0.01). But there was no significant variation in modification of volume of distribution (Vd). The results suggested that there is a significant drug interaction between atropine and theophylline.     

No influence of doxycycline on theophylline pharmacokinetics

The influence of the antibiotic drug doxycycline on steady-state pharmacokinetics of theophylline was studied in nine healthy adults by comparing the pharmacokinetic parameters measured during a 9-day course of theophylline alone and during comedication with doxycycline. Theophylline plasma concentrations were measured by means of high performance liquid chromatography analysis. Trough theophylline plasma concentrations were measured on days 1-8. On day 9 of each of the two periods of drug administration, a plasma concentration-time curve was evaluated. No influence of doxycycline on absorption, elimination, and volume of distribution of theophylline was found. Mean steady-state plasma concentrations were not significantly different during the two treatments. It is concluded that the drugs can be given concomitantly without any dosage adjustment of theophylline.