国产氨茶碱缓释片的人体药代动力学

本文采用荧光偏振免疫分析法测定了6例健康受试者口服单剂量国产氨茶减缓释片的血药浓度,并计算其药代动力学参数,结果表明:茶碱缓释片代谢为一室开放模型,其药动力学参数Tlag为0.53±0.29h,Ka为0.99±0.26h~(-1),Ke为0.0629±0.012h~(-1),Tmax为3.53±0.44h,t1/2为11.02±0.29h,Cmax为6.47±2.12μg/ml,AUC为122.6±38.1μg/ml.h,CL为1.03±0.22ml/min.kg。茶碱缓释片与普通氨茶碱片相比较,具有血药浓度下降缓慢,波动较小等特点,是一个较好茶碱剂型。     

氨溴索注射液对茶碱在家兔体内药动学的影响

目的 :研究氨溴索注射液对茶碱在家兔体内药动学的影响。方法 :采用自身对照法 ,用高效液相色谱法 (HPLC)测定合用氨溴索后 ,茶碱不同时间间隔血药浓度 ,采用 3P97程序进行模型判别及参数计算。结果 :合用氨溴索注射液后茶碱的t1/ 2 β由 (3.2± 0 .8)延长至 (4.0± 1.1)h(P <0 .0 5 ) ;AUC由 (75 .0± 2 2 .4 )增至 (98.2± 2 7.9)mg·h·L-1(P <0 .0 1) ;CL由 (0 .2 0± 0 .0 8)下降至 (0 .15± 0 .0 4 )L·h-1(P <0 .0 5 )。结论 :氨溴索注射液与茶碱在家兔体内合用可影响茶碱的t1/ 2 β、AUC、CL。     

环丙沙星对多索茶碱药物动力学的影响

目的 研究环丙沙星对多索茶碱在家兔体内的药物动力学的影响。方法 采用RP-HPLC法,测定10只家兔多剂量服用盐酸环丙沙星片前、后,口服多索茶碱的血药浓度,以3p87药动学软件按二室模型对数据进行处理并进行统计分析。结果 单用和合用环丙沙星后多索茶碱的Tmax分别为0.44±0,26 h、0.50±0.28 h,Cmax分别为4.93±2.75、5.72±3.04 μg·ml-1,T1/2β分别为7.36±2.96 h、9.35±3.38 h,AUC0→t分别为12.86±7.88、17.40±7.64μg·h·ml-1。 结论 两药联用时,环丙沙星对多索茶碱的Tmax和Cmax没有影响,对T1/2β和AUC0→t有影响,抑制了多索茶碱的代谢排泄。     

猪静脉注射青霉素G钾的药物动力学参数

本文对青霉素G钾在猪体内的药物动力学特征进行了分析,6头猪体重29.3±1.1kg(平均值±标准差),按每kg体重静脉注射单剂量青霉素G钾15000IU,给药后分别在0,5,10,15,30,45min及1,1.5,2,3h收集血样,采用微生物法测定血清青霉素G的浓度。以电子计算机程序处理血药浓度—时间数据,血药浓度随时间变化符合二室开放模型,所得主要动力学参数为:分布半衰期(t1/2α)0.14±0.03h;消除半衰期(t1/2β)0.70±0.21h;表观分布容积(Vd)0.696±0.141 l/kg;体清除率(Cls)11.67±1.02 ml/(kg·min);药时曲线下面积(AUC)21.57±1.93h·IU/ml,本文还根据单剂量给药参数推算给药方案,供兽医临床参考。     

红霉素对苯巴比妥药物动力学的影响

目的　研究红霉素对苯巴比妥药物动力学的影响。方法　 6只家兔 ,分为 2组 ,一组灌服红霉素 5 0mg·kg-1·d-1,共 5d ,另一组给予同量的生理盐水 ,一周后两组家兔对换给药 ,于第 3次给药后 1h肌肉注射苯巴比妥钠注射液 6mg·kg-1,0 2 5、0 5、1、2、4、8、12、2 4、4 8、72h分别取耳静脉血 ,FPIA法测定苯巴比妥的血药浓度并进行药物动力学分析。结果　家兔肌肉注射苯巴比妥钠 6mg·kg-1后的主要药动学参数为Tmax=1 4 1± 0 4 1h ,Cmax=16 11± 1 2 5 μg·ml-1,CL/F =0 0 0 9± 0 0 0 0 2mg·min-1,AUC =6 6 1.5 2± 5 3.88μg·ml-1·h ,T1/ 2 (Ka) =0 2 0± 0 0 6 7h ,T1/ 2(Ke) =2 7 5 4± 2 35h ;伍用红霉素组为Tmax=1 97± 0 5 9h ,Cmax=17 4 0± 1 10 μg·ml-1,CL/F =0 0 0 6± 0 0 0 0 6mg·min-1,AUC =92 5 .82± 87.5 9μg·ml-1·h ,T1/ 2 Ka =0 .2 8± 0 .10h ,T1/ 2 (Ke) =35 .5 1± 2 .76h。说明红霉素能显著降低家兔体内苯巴比妥的清除速率 (P <0 0 5 ) ,使苯巴比妥的曲线下面积增大 (P <0 0 5 ) ,消除半衰期明显延长 (P <0 0 5 ) ;红霉素对家兔体内苯巴比妥的吸收过程无明显影响 (P >0 0 5 )。结论　临床合并使用红霉素和苯巴比妥时应及时监测苯巴比妥的血药浓度 ,防止     

甲磺酸帕珠沙星氯化钠注射液在健康人体的药代动力学

目的研究甲磺酸帕珠沙星氯化钠注射液在健康人体的药代动力学。方法8名健康受试者单次静脉滴注甲磺酸帕珠沙星300,600mg后,用高效液相色谱法测定体内帕珠沙星的血药浓度,用DAS统计软件进行数据处理。结果结果符合一级消除药代动力学的二室模型,300,600mg2个剂量组的药代动力学参数:Cmax分别为(7.38±0.85),(18.36±2.39)mg·L-1;AUC0-t分别为(31.34±5.67),79.20±18.43)mg·h·L-1;t1/2β分别为(1.63±0.31),(1.71±0.21)h;CL/F分别为(0.10±0.02),(0.08±0.01)L·kg·h-1,V/F分别为(0.23±0.03),(0.19±0.05)L·kg-1。24h尿药累积排泄率分别为(92.2±2.6)%和(93.2±3.0)%。结论甲磺酸帕珠沙星每日给药300mg,每日2次,可达到有效治疗浓度,在600mg内可安全耐受。     

地红霉素片的人体药代动力学及生物利用度研究

目的　考察国产与进口地红霉素片的药代动力学及生物等效性。方法　采用随机单剂二交叉试验设计,18名健康男性志愿者单剂口服国产与进口地红霉素片 75 0mg,微生物法测定地红霉素血浓度。对二种制剂的主要药代动力学参数进行方差分析、双向单侧t检验,评价试验制剂与参比制剂的生物等效性。结果　国产和进口地红霉素片主要药代动力学参数t1/2ke分别为 19 77± 4 5 1h和 18 5 7± 3 39h,Tpeak分别为 3 89± 0 76h和 3 83± 0 5 1h,Cmax分别为 1 6 12± 0 176 μg·ml-1和1 6 85± 0 10 8μg·ml-1,AUC0～ 96h分别为 11 4 0± 1 88μg·ml-1·h和 11 0 5± 1 84 μg·ml-1·h,AUC0～∞ 分别为 12 14± 2 11μg·ml-1·h和 11 6 6± 1 88μg·ml-1·h,国产地红霉素片相对生物利用度F为 10 3 79%± 10 5 2 %。结论　国产与进口地红霉素片为生物等效制剂。     

左氧氟沙星对多索茶碱在健康人体内药动学的影响

目的研究合用左氧氟沙星对健康受试者多索茶碱血药浓度和药动学的影响。方法对10名男性健康受试者采用自身对照交叉试验设计方法给药,用高效液相色谱(HPLC)法测定多索茶碱血药浓度,采用3P97软件进行数据处理,求出药动学参数。结果合用左氧氟沙星组(试验组)多索茶碱平均血药浓度在停药后0～6 h各时间点(除停药后15 min)与单用多索茶碱组(对照组)相比均无显著差异(P>0.05);对照组和试验组多索茶碱的t_(+β)分别为(1.20±s 0.08)、(1.40±0.25)h;AUC分别为(16±4)、(17±3)mg·h·L~(-1);CL分别为(35±6)、(35±10)L·h~(-1);t_(+α)分别为(0.052±0.013)、(0.33±0.27)h;V_d分别为(6.1±2.1)、(34±30)L。合用左氧氟沙星后多索茶碱的V_D和t_(+α)的增加有显著差异(P<0.05),其余药动学参数在2组间均无显著差异(P>0.05)。结论合用左氧氟沙星对多索茶碱的代谢动力学无影响,但可改变其分布动力学,增大t_(+α)和V_d,2药合用不会引起多索茶碱的体内蓄积,提示2药合用相对安全。     

紫杉醇在卵巢癌化疗病人中的非线性药物动力学(英文)

目的:探讨紫杉醇在卵巢癌病人体内的药物动力学特点。方法:15名紫杉醇化疗病人3小时内输注剂量分别为135mg/m~2,175mg/m~2和235mg/m~2。输注过程中及输注后24小时采集病人血样。由非房室和房室模型评价药物动力学参数。结果:化疗病人符合二室模型,三组的T_((1/2)β)分别为(5.18±3.49,6.26±2.21和6.99±1.45)h,AUC(14.71±0.76,39.09±13.10和66.52±12.23)mg·h·L~(-1),Cl(14.29±0.74,7.52±2.15和6.25±1.93)L·h~(-1)。结论:紫杉醇具有非线性药物动力学特征,病人的代谢存在个体差异。     

对乙酰氨基酚咀嚼片相对生物利用度测定

2名健康受试者一次po两种对乙酰氨基酚咀嚼片后,用高效液相法测定ab的血药浓度。其血药农度和过程符合一室模型。国产对乙酰氨基酚咀嚼片A(tempra A)的药代动力学为:T1/2Ka=0.3806±0.2816h,T_(1/2)K_e=1.761±0.8930h,T_(max)=0.9023±0.4179h,C_(max)=7.0728±1.2264mg/L AUC=26.8579±10.7680μg·ml~(-1)·h~(-1)。tempra B的药代动力学为:T_(1╱2)Ka=0.2993±0.2584h,T_(1╱2)Ke=1.9720±0.470h,T_(max)=0.8322±0.5263h,C_(max)=6.7487±2.1925mg/L,AUC=25.0871±5.7059μg·m1~(-1)·h~(-1),国产对乙酰氨基酚痛咀嚼片与进口对乙酰氨基酚咀嚼片B(tempra B)的相对生物利用度为107.06％。提示两种对乙酰氨基酚咀嚼片的生物利用度相仿。     

Comparative effect of famotidine and cimetidine on the pharmacokinetics of theophylline in normal volunteers.

The comparative effect of famotidine or cimetidine on theophylline disposition was determined in healthy volunteers. Cimetidine, but not famotidine, caused a reduction in the rate of elimination of theophylline. The mean total body clearance of theophylline was reduced from 57.6 ml min-1 before cimetidine to 39.5 ml min-1 during cimetidine; and the half-life was prolonged from 8.7 h before cimetidine to 12 h during cimetidine. The volume of distribution and renal excretion of theophylline were not affected by either famotidine or cimetidine.     

Effects of equimolar doses of cimetidine and ranitidine on theophylline elimination

The disposition of theophylline was studied on four occasions in eight healthy adult males. The control mean theophylline half-life and clearance were 7·32 h and 0·86 ml min^?1kg^?1, respectively. After 5 days pretreatment with placebo the corresponding values of 7·01 and 0·88 were not significantly different, as were those of 7·43 and 0·85 after 5 days pretreatment with ranitidine (1·2g daily). Five days pretreatment with cimetidine (1·0g daily) resulted in a significant 44·4 per cent rise in the mean theophylline half-life and a 36·1 per cent fall in clearance. The fall in clearance correlated positively (r=0·9407) with the initial value. The volume of distribution did not change significantly throughout the study period. The fact that, at as large a dose as 1·2g daily, ranitidine did not impair theophylline metabolism suggests that similar results reported earlier with therapeutic doses of 300 mg daily cannot be ascribed to the lower dose of ranitidine employed. It is also suggested that the risk of theophylline toxicity consequent on cimetidine coadministration will be more likely in individuals with initial high theophylline clearance.     

The interaction between chronic oral slow-release theophylline and single-dose intravenous erythromycin

1. Eight volunteers were each given 300mg of erythromycin lactobionate by i.v. infusion over 15 min in the presence and absence of chronic dosing with slow-release theophylline.

2. Pharmacokinetic profiles were obtained for theophylline in the presence and absence of erythromycin and for erythromycin in the presence and absence of theophylline.

3. A very small, clinically unimportant, but statistically significant increase occurred in mean (± S.E.M.) serum theophylline concentration from 4.9 ± 0.3 mg/1 to 5.2±0.3 mg/1 in the presence of erythromycin (P = < 0.01). The theophylline pharmacokinetic parameters did not change significantly.

4. The only changes in erythromycin pharmacokinetics were an increase in the renal excretion (0–12h) from 5.5±4.0 mg to 11.2±6.0 mg (P < 0.03) and an increase in renal clearance (0–2h) from 9.0±6.0 ml/min to 21.6±15 ml/min (P < 0.05) in the presence of theophylline.     

依卡倍特二钠颗粒在健康人体中的单次给药药代动力学研究

目的研究中国健康志愿者单剂量口服2.0、4.0g依卡倍特二钠颗粒后的药代动力学行为,并评价药代动力学参数在2.0～4.0g范围内剂量相关性。方法 10名健康志愿者,随机交叉试验,分别单剂量口服依卡倍特二钠颗粒2.0、4.0g;测定给药后36h内的血药浓度。结果单剂量口服2.0、4.0g依卡倍特二钠颗粒后,依卡倍特的t1/2分别为(11±5)h和(9±4)h,达峰浓度(Cmax)分别为(4 998±982)ng/mL和(11 699±4 143)ng/mL,AUC0～t分别为(43 863±10 341)ng.h-1.mL-1和(92 492±30 915)ng.h-1.mL-1,AUC0～∞分别为(48 611±15 029)ng.h-1.mL-1和(99 628±35 993)ng.h-1.mL-1。结论在2.0～4.0g剂量范围内依卡倍特呈线性药代动力学,Cmax、AUC的升高与剂量成正比。     

Effect of cimetidine on the pharmacokinetics of theophylline

1. The effect of the therapeutic doses of cimetidine (400 mg/twice daily) on theophylline metabolism in Jordanian volunteers was studied. 2. The administration of the above therapeutic cimetidine dose did not alter theophylline clearance and elimination half-life. 3. Cimetidine administration also failed to alter the elimination of theophylline metabolites in urine.     

The effects of erythromycin on the absorption and disposition kinetics of theophylline

Summary The effects of erythromycin on the kinetics of theophylline were investigated in eight female patients with documented asthma in a crossover study. Theophylline pharmacokinetics were determined at steady state before and after one-week treatment with erythromycin stearate 250 mg given four times a day. Multiple serum samples were collected for 12 h after an aminophylline dose in the two drug treatment phases and assayed by high performance liquid chromatography. The resultant serum theophylline concentration-time data were analyzed by weighted, nonlinear regression analysis to obtain various pharmacokinetic parameters. In this study, the elimination half-live increased from 7.8±1.7 h on the control day to 9.5±1.4 h following treatment with the antibiotic (p<0.02). The estimated apparent volume of distribution for theophylline (V/F) was also observed to increase from 0.42±0.09 l/kg before treatment with erythromycin to 0.53±0.15 l/kg after antibiotic treatment (0.05<p<0.10). In this study, no difference was demonstrated in the apparent clearance rate (Cl_app), apparent first-order absorption rate constant (k_a), maximum serum drug concentration (C_max), time of maximum drug concentration (T_max) or absorption lag time (t_lag) for theophylline before and after treatment with erythromycin. With no apparent alteration in theophylline clearance following erythromycin coadministration, the decrease in the first-order elimination rate constant suggested that the apparent volume of distribution of theophylline is increased in the presence of erythromycin. It is concluded that patients maintained on theophylline derivatives should be closely monitored when erythromycin is coadministered.     

Etintidine-theophylline interaction study in humans

Etintidine HCl is a potent H2-blocker. The effect of clinical doses of etintidine on the disposition of theophylline was investigated in 10 male volunteers. This was a double-blind, two-way crossover study. Each subject received etintidine (400 mg) or placebo twice a day with meals for 4 days on two occasions (separated by 4 days). On each occasion, the subjects were fasted overnight on Day 3 and were given an oral dose of theophylline elixir (5 mg/kg) 30 min following the administration of the morning dose of etintidine or placebo on Day 4. Blood samples were collected prior to and up to 24 h following the administration of theophylline. Plasma theophylline levels were analysed by HPLC. Theophylline was rapidly absorbed following oral administration of the theophylline elixir to both the placebo and etintidine treatment groups. Comparison of the pharmacokinetic parameters of theophylline between the etintidine and the placebo groups indicates that while etintidine did not significantly (p greater than 0.05) affect the apparent Cmax (11.1 vs 10.0 micrograms ml-1) and Tmax (1.7 vs 1.4 h) values of theophylline, etintidine significantly reduced the oral clearance (0.0200 vs 0.0564 l kg-1 h-1, p = 0.000006) and prolonged the elimination half-life (16.8 vs 6.0 h) of theophylline. The data indicate that etintidine, like cimetidine, extended the elimination of theophylline in humans.     

Effect of Tamoxifen on the Pharmacokinetics of Theophylline in Rats

The effect of tamoxifen on the pharmacokinetics of theophylline was investigated in male Sprague–Dawley rats. The oral administration of tamoxifen at a dose equal to 40 mg kg^?1 48 h before the intravenous injection of theophylline 10 mg kg^?1, significantly (P < 005) increased the clearance of theophylline by 39%, with no apparent effect on the volume of distribution. As a consequence, the elimination half-life of theophylline was significantly (P < 005) shortened in the tamoxifen-treated rats (3.56 ± 0.39 h vs 5.25 ± 0.48 h) as well as its mean residence time (5.04 ± 0.60 h vs 7.50 ± 0.75 h). Although these data cannot be directly extrapolated to the clinical situation, they provide experimental support to suggest that more attention should be paid to the potential risk of pharmacokinetic interactions in the presence of tamoxifen.     

Bioavailability and Pharmacokinetics of Sublingual Oxytocin in Male Volunteers

The aim of this investigation was to assess the bioavailability and pharmacokinetics of oxytocin in six male subjects after a sublingual dose of 400 int. units (684 μg) and after an intravenous dose of 1 int. unit (1·71 μg). After intravenous administration, the pharmacokinetic profile could be described with a two-compartment model. The distribution half-life was 0·049 ± 0·016 h, the elimination half-life was 0·33 ± 0·23 h, the total body clearance was 67·1 ± 13·4 Lh^?1 and the volume of distribution was 33·2 ± 28·1 L. After sublingual administration, a poor bioavailability with a 10-fold variation between 0·007 and 0·07% was observed. The pharmacokinetic profile could be described with a one-compartment model. The lag time was subject-dependent and ranged between 0·12 and 0·30 h (40% CV). The absorption half-life was 0·45 ± 0·29 h, and the apparent elimination half-life 0·69 ± 0·26 h. This study showed a very poor and interindividual variability in bioavailability. The sublingual route of administration with its ‘long’ lag time and ‘long’ absorption half-life would not seem a reliable route for accurate high dosing for immediate prevention of post-partum haemorrhage.     

双黄连对氨茶碱药动学的影响

目的 :研究双黄连对氨茶碱在人体内药动学的影响。方法 :采用高效液相色谱法测定8名健康志愿者多剂量服用双黄连口服液前、后氨茶碱的血药浓度 ,以3p97药动学软件按一室模型对数据进行处理 ,并对结果进行统计学分析。结果 :单用氨茶碱和合用双黄连后氨茶碱的Tmax 分别为 (1 66±0 56)、(1 59±0 78)h ,Cmax 分别为 (6 23±1 31)、(6 10±0 94) μg/ml ,T1/2 分别为(5 76±1 11)、(6 09±1 63)h ,CL分别为 (47 72±5 12)、(50 98±10 85)ml/(kg·h) ,Vd分别为 (369 18±40 15)、(430 37±48 33)ml/kg,AUC0→∞分别为 (84 56±14 43)、(89 27±26 35) μg/(h·ml)。结论 :双黄连明显增加氨茶碱的Vd ,对Tmax、Cmax、T1/2、CL和AUC0→∞没有影响