茶碱经微处理机程序输注迅速达到期望兔血浆稳态水平

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，体重及时间。输注速率（Ｋ）＝ＣｐｓｓＫ１０Ｖｃｗｔ｛１＋［（Ｋ２１－β）／β］ＥＸＰ（－Ｋ２１ｔ）｝，血药浓度预报式为Ｃ（ｔ）＝Ｃｐｓｓ（１－ｅ＾ａｔ），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Ｔ１２β＝６．０８ｈ，但输注后３０ｍｉｎ，血药浓度达期望     

茶碱经微处理机程序输注迅速达到期望兔血浆稳态水平(英文)

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)。     

普鲁卡因程序输注的实验研究

自制程序输液泵应用于普鲁卡因静脉输注。向程序输液泵输入犬普鲁卡因药代动力学参数（Ｖｃ，Ｋ１０，Ｋ２１，β），预期血药浓度，体重及输注时间。自动显示所需药液浓度和体积，配制药液后，启动输液泵自动输注。用高效液相色谱法测定血浆普鲁卡因浓度。结果：９５％的执行百分误小于±３０％，其绝对值的中位数仅９．７％。提示我们的程序输注是可取的。     

何谓“指数滴注”?临床上有何用途?

[答]:指数滴注(exponential infusion)指静脉滴注过程中,滴注速率是时间的指数衰减函数,即单位时间内进入体内的药量随时间作指数衰减。这种血管内途径给药方法的目的是根据体内药量的逐渐增加,使血药浓度在安全范围内尽快地达     

口服吗丁啉对氨茶碱血药浓度及药动学参数的影响

本文采用紫外分光光度法分别测定氨茶碱单用及合用吗丁啉后兔血清中茶碱浓度,结果表明,两药合用后吸收呈双峰,一峰较单服茶碱提前约2h,一峰推后约3h,血药峰浓度下降,维持有效血浓度的时间延长,波动相对减小,K.,K,T_(1/2),AUC 无显著性差异(P>0.05),T_(pk)有显著性差异(P<0.05),揭示两药合用时给药时间应调整,并同时监测血药浓度。     

克拉霉素对茶碱在兔体内药动学的影响

目的研究克拉霉素对茶碱在新西兰兔体内药动学的影响.方法采用自身对照法,用HPLC测定合用克拉霉素后,茶碱不同时间间隔血药浓度,经3P97程序进行模型判别及参数计算.结果合用克拉霉素注射液后茶碱的t1/3β由(3.24±0.76)h延长至(4.90±1.16)h(P＜0.01);AUC由(75.02±22.41)mg·h·L-1增至(98.18±27.91)mg·h·L-1(P＜0.01);CL由(0.20±0.08)L·h-1下降至(0.13±0.04)L·h-1(P＜0.05).结论克拉霉素注射液与茶碱在兔体内合用可影响茶碱的t1/3β,AUC,CL.     

血清中茶碱荧光偏振免疫测定试剂盒的研制

本文报道一种新的茶碱ＦＰＩＡ试制盒的研制工作，包括７－氨基丁基－茶碱－ＤＴＡＦ轭合物的设计合成，兔抗茶碱血清的制备、方法学考核及与进口同类试剂盒和紫外法作相关性研究等。实验结果表明，国产茶碱ＦＰＩＡ试剂盒的各项分析指标已能满足药物监测的要求，而且，在茶碱血清浓度监测和药代动力学研究中有较好的推广价值。     

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.     

注射用双黄连对兔体内茶碱药物动力学参数的影响

目的:探讨注射用双黄连对兔体内茶碱药物动力学参数的影响.方法:取家兔8只,采用自身对照法.首先静注氨茶碱注射液10 mg·kg-1,6 d后静注注射用双黄连196 mg·kg-1,qd,联用4 d,于第4天同时给予氨茶碱10 mg·kg-1,用TDx测定茶碱血清浓度,计算机拟合房室模型并计算药动学参数.结果:氨茶碱的药-时曲线符合一室模型.合用注射用双黄连前后,茶碱半衰期、消除速率常数、消除率、曲线下面积及表观分布容积均无显著变化(P＞0.05).结论:注射用双黄连对家兔体内氨茶碱药动学参数影响甚少,两药合用可能是安全的.     

氨茶碱血药浓度的监测

<正> 氨茶碱是一种有效的支气管扩张药。由于其治疗指数低,毒副作用大,个体差异也大。因此必须对其血药浓度进行监测,调整给药方案,实现个体化给药是很有必要的。 我们根据医院实际及临床具体情况,采用平均参数来监测茶碱血浓度,调整给药方案,即通过测定患者的茶碱最低稳态血浓度,     

Evaluation of infusion regimens for thiopentone as a primary anaesthetic agent

Summary Several multi-stage infusion regimens and a computer controlled exponentially decreasing infusion regimen were evaluated in twelve patients undergoing head and neck surgery or neurosurgery. Thiopentone dosage was based on the mean of pharmacokinetic parameter values from the literature and adjusted for each patient's lean body mass in order to rapidly achieve a predetermined plasma thiopentone concentration of 15 or 20 µg/ml in the period following the initial bolus dose to induce anaesthesia. Anaesthesia was satisfactory in all cases. Plasma thiopentone concentrations were maintained between 10–20 µg/ml during infusion in the five patients who received either a four or five stage infusion and in the six patients who received the exponential infusion, but not in the single patient who received a two-stage infusion. The mean recovery time was 111 min. The plasma concentrations of total and unbound thiopentone at awakening showed little intersubject variability, despite considerable differences in total dose and duration of infusion, suggesting the absence of acute tolerance to the drug. Plasma clearance of total thiopentone correlated strongly with calculated lean body mass and to a lesser extent with total body weight suggesting that lean body mass, in particular, should be an accurate predictor of thiopentone maintenance dose requirements. This study shows that it is feasible to use thiopentone as a primary anaesthetic agent during surgery by administering the drug either as an exponentially decreasing infusion or as an infusion comprising 4 or 5 stepwise decreasing rates.     

Pharmacokinetics of isosorbide dinitrate after intravenous infusion in human subjects

Plasma concentrations of isosorbide dinitrate have been measured after intravenous infusion of drug at a rate of 5·0 mg h^?1 for 150 min and after single equal oral doses of 12·5 mg of drug in solution to two normal human subjects. During the infusion, uneven plateau concentrations were approached after 30 min. The calculated average steady-state plasma levels were 258 ng ml^?1 and 514 ng ml^?1 in the two subjects respectively. The half-life of elimination of isosorbide dinitrate after termination of the infusion was 9–10 min. After oral doses, peak plasma levels of 26·6 ng ml^?1 and 12·7 ng ml^?1 occurred at 10 min and 20 min in the two subjects respectively. The terminal half-life of drug after the oral doses was much longer than the elimination half-life (about 10 min), and was associated with the absorption phase. Fairly good agreement was obtained between the observed concentrations and those predicted by a one-compartment open model. The systemic availability of isosorbide dinitrate after the oral doses was up to only 3 per cent of the equal doses infused, indicating that presystemic elimination processes accounted for very large proportions of the oral doses. The systemic clearances of drug after infusion of 0·32 1 min^?1 and 0·161 min^?1 were unexpectedly low for a drug of reported high liver extraction ratio.     

Rectal infusion of the model drug antipyrine with an osmotic delivery system

An osmotically-powered rectal drug delivery system, was used for the rectal infusion of the model drug antipyrine. The system, which is slightly larger than a normal suppository, has a nominal pumping rate of 43 μl h^{? 1} over at least 30 h. Four healthy volunteers kept two such systems in their rectum for a sum total of 98 h. Saliva and plasma concentrations were determined at regular intervals and in all cases a very constant steady-state saliva and plasma concentration was reached and maintained. Defecation and reinsertion of the drug delivery system did not cause any irregularities in the concentration profile. The system was very well tolerated by the volunteers.     

由静脉恒速滴注血药浓度计算双室模型药物动力学参数的微分法

目的：建立一种根据血药浓度的微分特征计算静脉滴注双室模型药物动力学参数的新方法。方法：通过微分方法分析双室模型药物静脉滴注给药的血药浓度达到稳态前的药物动力学特征，求出药物的中央室分布容积、双室模型药物在隔室间的转运速率常数，并据此计算快速配置速度常数和慢速配置速度常数等参数。结果：得到了双室模型药物的中央室分布容积V1，双室间的转运速率常数κ12、κ21、κ10，快速配置速度常数α和慢速配置速度常数β等主要药物动力学参数的计算方法。模拟计算结果表明，本法具有良好的准确性。结论：以恒速静脉滴注血药浓度的微分法计算双室模型药物的药动学参数，具有快速、样本少、血药浓度无须达稳态的优点。     

Relationships among duration of infusion,dose, dosing interval,and steady-state plasma concentrations during intermittent intravenous infusions: Studies with metronidazole

Relationships among duration of infusion (T), dose, dosing interval (), maximum and minimum plasma drug concentrations at steady state (C_max,ssand C_min,ss, respectively), and the duration of effective plasma concentrations (t_D) during multidose intermittent infusion regimens were studied by computer simulation using metronidazoie as a model drug. Pharmacokinetic parameter values for metronidazole were obtained from the literature and the minimum effective plasma concentration (MEC) was taken as 6.0 g/ ml. Increasing the infusion period of the dose reduces C_max,ss, but increases C_min,ss. If intermittent bolus injection of a given dose of drug results in effective plasma concentrations for the entire dosage interval (i.e., C_min,ss,bolus> MEC), then infusion of that dose over any period (T) will also result in effective concentrations for the entire dosage interval. However, if the dosage is such that C_min,ss,bolus < MEC, the relationships among duration of infusion, dose, dosage interval, and duration of effective plasma concentrations are complex. Therefore a nomogram was developed to allow selection of dose, dosing interval, and infusion period such that C_max,ss and C_min,ss could be maintained within a desired range.     

Influence of intravenous infusion duration on the tissue drug concentration profile

The influence of intravenous infusion duration of a single dose of drug on the time course of drug concentration in the peripheral compartment of the classical two-compartment pharmacokinetic model was studied by computer simulation. The aim was to illustrate the general relationships among infusion duration T,dose, minimum effective concentration MEC at the effector (tissue) site, maximum tissue drug concentration C_2,max,and the duration of effective tissue concentrations t_{D.tiss for those drugs where there is an equilibration delay between concentration at the effector site and plasma. Simulations of} C_2,max vs. Tfor meperidine, sulfamethoxazole, ampicillin, and metronidazole showed that, although maximum plasma concentration may decrease markedly with increasing T, C_2,max decreased only slightly with increasing T.Simulations of the influence of Ton the duration of effective plasma concentrations t_D and t_{D,tiss of metronidazole showed that for a given} T, t_{D,tiss may be greater than or less than} t_D,depending on the dose, and that it is possible to obtain effective concentrations in the tissue compartment even though the infusion duration is too long to achieve effective concentrations in plasma. It was found that, depending on the dose, it was possible to cause an increase in t_{D,tiss compared with bolus administration by increasing the infusion duration of the dose. It was also found that increasing} Tcould cause opposite changes in t_D and t_{D,tiss (compared with bolus administration, respectively), e.g., an increase in} t_D and a decrease in t_{D,tiss or vice versa, depending on the dose. It should thus be possible to make precise predictions of the influence of} Ton drug concentration at the effector site for individual drugs by incorporating effect compartment modeling into the analysis.     

Plasma Concentration Clamping in the Rat Using a Computer-Controlled Infusion Pump

We have developed a computer-controlled infusion pump to achieve rapidly and then maintain stable plasma thiopental concentrations in rats. Initially we derived the parameters of a triexponential pharma-cokinetic model for thiopental, administered as a brief infusion to 10 rats, using nonlinear regression and standard pharmacokinetic equations. These parameters were incorporated into the pharmacokinetic model of a computer-controlled infusion pump. In a second group of animals this device was used to maintain three consecutive target thiopental concentrations ranging from 5 to 100 µg/ml in a stepwise fashion. Arterial blood gases were kept normal through controlled ventilation when necessary. The plasma thiopental concentrations in this second group of animals were generally higher than the target concentrations. The bias in pump performance (median prediction error) was +25%, and the inaccuracy (median absolute prediction error) was 26%. We fit the parameters of a three-compartment model to the plasma thiopental concentrations observed in the second group of animals. This produced a second set of thiopental pharmacokinetic parameters with the unique characteristic of having been derived from a computer controlled infusion study. These parameters were tested prospectively with a computer-controlled infusion pump in a third group of animals. This second set of thiopental pharmacokinetic parameters performed better, with a median prediction error of 0% and a median absolute prediction error of 15%. This study shows that it is possible to achieve rapidly and maintain steady plasma thiopental concentrations in the rat. Our results suggest that it is feasible to derive robust pharmacokinetic parameters from unusual drug dosing approaches, such as employed by a computer-controlled infusion pump. The ability rapidly to clamp plasma drug concentrations at desired targets in small laboratory animals will facilitate research into the relationship of plasma and tissue concentration to drug effect.     

The effect of infusion time on the time course of drug concentration in blood

We have studied by digital computer simulation the relationships among the rate of intravenous infusion of the dose of a drug, the pharmacokinetic parameters of the drug, the maximum blood drug concentration achieved (C_max) and the interval (T_Eff) during which the blood concentration of the drug is maintained above a selected minimum effective concentration (C_Eff) for the case of single dose administration of a drug with monoexponential pharmacokinetics. It was found that increasing the time during which the dose of the drug is infused results in a much smaller decrease in the maximum blood concentration attained. The interval, T_Eff, was found to be a function of the ratios infusion time/ drug elimination half-life and zero-time intercept (C₀)/ C_ff The simulations showed that T_Eff varies nonlinearly with increasing infusion time. However, the nature of the relationship between T_Eff and infusion time depends very much on the value of C₀/C_Eff. At low values of C₀/C_Eff, T_Eff decreased almost linearly with increasing infusion time, but at higher values of C₀/ C_Eff, T_Eff increased for a time with increasing infusion time. From these simulations, it should be possible to predict whether therapeutically effective blood concentrations of a drug may be achieved with the use of a slower infusion in situations where clinical considerations necessitate that the infusion time of the dose be increased.     

Pharmacokinetic approach for reconstruction of predetermined plasma insulin profiles by continuous subcutaneous insulin infusion in depancreatized dogs

A preprogrammable insulin delivery system which can provide the flexibility of varying plasma insulin concentration in a physiological manner has been developed. This system involves a program of continuous subcutaneous infusion of insulin at variable rates to reproduce arbitrarily selected plasma insulin concentration-time profiles. The desired insulin infusion rate profile was calculated from the desired insulin pattern using pharmacokinetic parameters experimentally determined by measurement of immunoreactive plasma insulin following a subcutaneous bolus dose to depancreatized dogs.