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排序方式: 共有724条查询结果,搜索用时 15 毫秒
61.
Teunissen Michael W. E. Brorens Irinka O. N. De Langen H. Joke Geerlings Anne M. Breimer Douwe D. 《Pharmaceutical research》1986,3(3):156-161
Two model substrates for oxidative hepatic enzyme activity, viz. antipyrine (A) and theophylline (T), were given simultaneously to rats by iv administration. Blood concentrations of A and T were measured by a high-performance liquid chromatographic (HPLC) method. Urinary excretions of A, T, and the major metabolites arising from A—4-hydroxyantipyrine (OHA), norantipyrine (NORA), 3-hydroxymethylantipyrine (HMA), and 4,4-dihydroxyantipyrine (DOHA)—and from T—1-methyluric acid (1-MU) and 1,3-dimethyluric acid (1,3-DMU)—were also determined by HPLC. It was found that the pharmacokinetic parameters obtained after the simultaneous administration of A and T at relatively low dose levels (A, 5.0 mg; and T, 1.3 mg) were not different from those obtained after the separate administration of A or T at the same dose level. In order to investigate whether the metabolic pathways of A and T are mediated by the same or closely related forms of the cytochrome P-450 system, metabolic clearances of A (CLA,M) and T (CLT,M) and the clearances for production of their various metabolites, obtained in untreated rats and in rats pretreated with 3-methylcholanthrene (MC) or with MC followed by 9-hydroxyellipticine (E), were correlated. These two compounds are a selective cytochrome P-448 inducer and inhibitor, respectively. Strong correlations were found between CLT,M and the clearances for production of OHA, NORA, and DOHA but not HMA. The best correlation, however, was observed between CLT,M and CLOHA, not only when all data points were taken into account (r = 0.99), but also in separate pretreatment groups (r ranging from 0.87 to 0.92). Moreover, the slopes of these correlation lines varied only slightly among groups, while the intercepts were not significantly different from zero. In the separate pretreatment groups, the correlation coefficients for the correlations between CLT,M and the clearance for production of the other metabolites of A were considerably lower, while the slopes of the correlation lines varied substantially. Clearances for production of the metabolites of T were strongly correlated with each other (r = 0.99) and with CLOHA (r = 0.95). It can be concluded that theophylline metabolism and formation of OHA are mediated by the same or very similar forms of cytochrome P-450, whereas formation of the other major metabolites of A is not or only partly. The study of the various pathways of metabolism after simultaneous administration of drugs is a powerful tool in the study of correlations in drug metabolism in vivo. 相似文献
62.
反相高效液相色谱法同时测定人血清中茶碱和多索茶碱的浓度 总被引:1,自引:0,他引:1
目的 建立反相高效液相色谱法同时测定人血清中茶碱和多索茶碱浓度的分析方法.方法 血清样品加入咖啡因为内标,三氯醋酸沉淀蛋白,采用Ultimate XB-C18(250 mm× 4.6mm,5μm)色谱柱分离,流动相为甲醇:水=30∶70,流速为1.0mL/min,检测波长为273 nm,柱温为30℃.结果 荼碱在0.97~48.40mg/L范围内,线性关系良好,r=0.9999;多索茶碱在1.10~54.80 mg/L范围内,线性关系良好,r=0.9998.日内精密度和日间精密度良好,荼碱、多索茶碱的低、中、高3种浓度方法回收率分别为6.01%、2.25%、0.86%和5.71%、2.02%、1.07%.结论 该法操作简便,结果准确可靠,可满足临床快速监测的需要. 相似文献
63.
T. Kokufu N. Ihara N. Sugioka H. Koyama T. Ohta S. Mori K. Nakajima 《European journal of clinical pharmacology》1995,48(5):391-395
The effect of the new substituted benzimidazole proton pump inhibitor, lansoprazole, on pharmacokinetics and metabolism of theophylline has been studied in healthy adults given oral lansoprazole 30 mg once daily for 11 days. On Days 4 and 11 of 300 mg aminophylline was simultaneously administered orally and blood samples for theophylline analysis were taken over 24 h. Urine samples were collected for up to 24 h and were assayed for theophylline and its major metabolites 1,3-dimethyluric acid (1,3-DMU), 1-methyluric acid (1-MU) and 3-methylxanthine (3-MX). The pharmacokinetic parameters of theophylline were determined, and the urinary recovery of unchanged theophylline and its major metabolites were calculated.After administration of lansoprazole for 4 days, no significant alteration in the terminal elimination half-life (t
1/2) or the mean residence time (MRT) was detected. However, there was a significant decrease of about 13% in the area under the plasma concentration-time curve (AUC) and a significant increase of about 19% in the apparent clearance (CLapp). Lansoprazole treatment for 11 days caused a significant decrease of approximately 12% in t
1/2 and about 10% in the MRT of theophylline, although neither AUC nor CLapp showed a significant alteration. The excretion of 3-MX in the urine was significantly increased by about 20% after lansoprazole treatment for 4 and 11 days, although there was no significant alteration in the excretion of unchanged theophylline, 1,3-DMU or 1-MU.The results indicate that repeated administration of lansoprazole to humans induces the hepatic microsomal P-450-dependent drug oxidation system that mediates N-1-demethylation of theophylline, consequently increasing its metabolism. 相似文献
64.
Theophylineisoneofthemostwidelyuseddrugsintreatingchronicobstructivepulmonarydisease(COPD).However,thetraditionaltheorythatth... 相似文献
65.
目的建立高效液相色谱法测定复方妥英麻黄茶碱胶囊中苯妥英钠的含量。方法采用Diamonsil钻石C18(150 mm×4.6 mm,5μm)色谱柱,以甲醇-水(50∶50)为流动相,检测波长为215 nm,流速为1.0ml/min,柱温设置为室温。结果 3批复方妥英麻黄茶碱胶囊及片剂的标示量为97.88%(20121202)、99.56%(20121203)、96.41%(20121204),102.9%(片剂)。结论本方法简便,结果准确可靠,可用于该制剂质量控制的有效方法。 相似文献
66.
Robert A. Upton Jean-Francois Thiercelin John K. Moore Sidney Riegelman 《Journal of pharmacokinetics and pharmacodynamics》1982,10(2):135-146
Bioavailability studies are commonly undertaken, and most, because they involve subjects taking repeated doses of a drug, contain information on intraindividual variability in pharmacokinetics. However, because in such studies bioavailability itself is unknown, it is difficult to resolve which pharmacokinetic parameters vary within individuals. A mathematical model is presented which permits estimation of variability in clearance and in volume of distribution. When applied to pooled data arising from five theophylline bioavailability studies, this model has given statistical evidence that clearance of theophylline is inherently more variable within individuals (coefficient of variation, 13%) than volume of distribution (8%). As a result, use of the measurement AUC · rather than AUCas a more precise index of bioavailability is justified in studies where is measured with reasonable precision. The model could be applied to estimation of withinbatch within-person variability in bioavailability.Deceased, April 4th, 1981. 相似文献
67.
68.
自制二室模型药物程序输液泵。向控制器输入兔茶碱药物动力学参数,期望血浆稳态浓度(C_(pss)),体重及时间。输注速率(K_t)=C_(pss)K_(10)V_cwt{1 [(K_(21)-β)/β]EXP(-K_(21)t)},血药浓度预报式为C_((t))=C_(pss)(1-e~(-αt)),依据显示配药液,自动输注。比色法测定血药浓度。96%的执行百分误小于±30%,其绝对值的中位数为8.3%。虽然T_2~1β=6.08h,但输注后30min(5T_2~1α),血药浓度达期望C_(pss)。 相似文献
69.
Anne E. Dixon David M. Shade Rubin I. Cohen Gwen S. Skloot Janet T. Holbrook Lewis J. Smith John J. Lima Hooman Allayee Charles G. Irvin Robert A. Wise 《The Journal of asthma》2006,43(7):553-558
Obesity is a risk factor for being diagnosed with asthma, but there is conflicting evidence on whether obesity is a risk factor for lung function abnormalities characteristic of asthma. We studied a cohort of 488 subjects, 47% of whom were obese. Obese and non-obese subjects with asthma had similar airflow limitation and bronchodilator responsiveness, but obese participants had increased sleep disturbance and gastroesophageal reflux disease, higher cytokine levels, and a trend towards increased exacerbations when treated with theophylline. Obese and non-obese asthmatics have similar lung function abnormalities, but comorbidities and altered responses to medications may significantly affect asthma control in obese people. 相似文献
70.
Yusuke Tanigawara Ikuko Yano Kazuo Kawakatsu Koichi Nishimura Masato Yasuhara Ryohei Hori 《Journal of pharmacokinetics and pharmacodynamics》1994,22(1):59-71
The present paper reports theoretical equations for the predictive performance of the Bayesian forecasting method. The precision
of parameter estimates and predicted concentrations for an individual was described by general equations with the aid of a
variance-covariance matrix of parameter estimates that involved the Bayes theorem. The equations were applied to assess the
predictive performance of the one-point Bayesian method in association with blood sampling time, the population parameters,
and the pharmacostatistical model. The simulation study showed that the prediction error in parameter estimates essentially
depended upon the sampling time but the magnitude of dependency was affected by the size of inter-and intraindividual variances.
With a smaller value of interindividual variance, the dependency on sampling time was less apparent. Effects of sampling time
were further examined using clinical data obtained from 20 patients taking theophylline, and the results were in good agreement
with the theoretical consideration. The present general equations are useful to investigate the sampling strategy as well
as structural and variance modeling on the predictive performance of the Bayesian method. 相似文献