硝苯地平对兔体内茶碱药物动力学的影响

为探讨硝苯地平耐氨茶碱的药代动力学的影响，采用反相高效浓相色谱法测定健康家兔静注氨茶碱注射液(12．5mg／kg)后和加服硝苯地平(20mg／kg)3无后静注氨茶碱注射液的茶碱浓度。结果表明，后的茶碱浓度(14.52±3.70mg／L)，较单用氨茶碱的血药浓度(27．43±7．61mg／L)明显下降。AUC减小，Vc增大(P<0．05)。比较两组其它药动学参数差异无显意义(P>0.05)．结论；硝苯地平对氨茶碱药动学性质未产生显影响，合并用药不需要调整氨茶碱剂量。     

酮康唑对家兔体内茶碱血药浓度及药动学参数的影响

目的观察酮康唑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分析法测定氨茶碱单用及与酮康唑合用后家兔体内茶碱血清浓度 ,并对两组药动学参数进行统计学处理。结果酮康唑可使氨茶碱血药浓度明显降低 ;合并用药组Vd为4.70±1.48L,AUC为51.94±25.51mg/(L·h) ,对照组Vd为1.39±0.61L,AUC为75.74±11.29mg/(L·h) ,两组相比有显著差异(P<0.01和P<0.05),其余药动学参数无显著变化。结论两药合用时应调整氨茶碱的给药量 ,并注意监测其血药浓度     

用药动学参数制订氨茶碱的给药方案

目的:通过文献报道的药动学参数(群体均值)设计氨茶碱的给药方案。方法:介绍口服维持剂量、静脉滴注维持剂量的滴速及静脉滴注负荷剂量的计算法;介绍药动学参数法与常规法和实测血药浓度法给药相比较的实例。结果:不同病理、生理状况需不同的剂量,不宜为每次1片,tid。结论:建议不能实测血药浓度的医院均采用药动学参数法制订氨茶碱的给药方案。     

地尔硫卓对兔体内茶碱药物动力学参数的影响

本文采用荧光偏振免疫分析法（ＦＰＩＡ）对单用氨茶碱及氨茶碱与地尔硫合用后，家兔体内茶碱血清药物浓度进行了测定，并对两组药动学参数进行了统计学处理，结果表明，地尔硫略使氨茶碱血药浓度升高，ＡＵＣ合并用药组与对照组有显著差异（Ｐ＜０．０５），其余药动学参数无显著变化。     

地尔硫Zhon对兔体内茶碱药物动力学参数的影响

本文采用荧光偏振免疫分析法（ＦＰＬＡ）对单用氨茶碱及氨茶碱与地尔硫Ｚｈｏｎ合用后，家兔体内茶碱血清药物浓度进行了测定，并对两组药动学参数进行了统计学处理，结果表明，地尔硫Ｚｈｏｎ略使氨茶碱血药浓度升高，ＡＵＣ合并用药组与对照组有显著差异（Ｐ〈０．０５），蓁药动学参数无显著变化。     

酮康唑对家兔体内茶碱血药浓度及药动学参数的影响

目的：观察酮康唑对茶碱血药浓度及药动学参数的影响。方法：采用荧光偏振免疫分析法测定氨茶碱单用及与酮康唑合用后家兔体内茶碱血清浓度，并对两组药动学参数进行统计学处理。结果：酮康唑可使氨茶碱血药浓度明显降低；合并用药组Vd为4．70±1．48L，AUC为51．94±25．51mg/(L·h），对照组Vd为1．39±0．61L，AUC为75．74±11．29mg/(L·h），两组相比有显差异（P＜0．01和P＜0．05），其余药动学参数无显变化。结论：两药合用时应调整氨茶碱的给药量，并注意监测其血药浓度。     

氨茶碱的临床用药实例分析

目的监测氨茶碱的血药浓度,合理使用氨茶碱。方法通过上报的氨茶碱不良反应报告,对氨茶碱血药浓度与疗效的关系进行分析。结果 9例应用氨茶碱患者分别合并应用喹诺酮类抗生素、H2受体阻断剂、抗心律失常药,血药浓度均高于氨茶碱的有效浓度20μg/mL,发生不良反应。结论临床使用氨茶碱应进行血药浓度监测,并结合患者的生理、病理、药动学、药物相互作用及临床疗效,保证个体化给药。     

克拉霉素对兔体内稳态时氨茶碱药代动力学的影响

目的：观察6只新西兰白兔灌服克拉霉素前后对稳态时氨茶碱血药浓度及药代动力学参数的影响。方法：采用荧光偏振免疫分析法测定氨茶碱血药浓度，实验为两组：Ⅰ期d1-4为单独灌服氨茶碱至稳态，Ⅱ期为d5-10，合用克拉霉素与氨茶碱，每次给药剂量氨茶碱为30mg.kg^-1，克拉霉素为50mg/kg^-1，对两组药物动力学参数进行统计分析。结果：两组各药动学参数比较均无显性差异。结论：氨茶碱与克拉霉素合并应用不需要调整氨茶碱的用量。     

头孢他啶对大鼠体内氨茶碱药动学的影响

目的通过检测茶碱在大鼠体内的血药浓度，分析头孢他啶对氨茶碱药动学参数的影响。方法12只大鼠随机分为两组，每组6只，给药前禁食12 h，对照组每只动物分别给予氨茶碱18 mg·kg^-1，灌胃1次。实验组给予氨茶碱18 mg·kg^-1，ig，并肌内注射头孢他啶100 mg·kg^-1，分别在给药前及给药后0.08，0.50，1.00，2.00，4.00，6.00，8.00，12.00 h采血0.3～0.5 mL，置不抗凝离心试管内，离心(10 000 r·min^-1)，取血清60 μL，用全自动荧光偏振免疫分析仪测茶碱血药浓度。结果茶碱以一室药动学模型消除，头孢他啶与氨茶碱合用与单用氨茶碱比较，药动学参数无明显变化。结论头孢他啶在大鼠体内对氨茶碱药动学无显著影响。     

尼群地平对兔体内茶碱的药动学影响

目的：研究氨茶碱与尼群地平合用时是否需调整其剂量。方法：建立以β－羟基茶碱为内标而检测血清茶碱的高效液相色谱法,８只大白兔于第１、７天单次静注氨茶碱１２．５ｍｇ．ｋｇ＾－１,第２～７天灌服尼群地平１０ｍｇ．ｋｇ＾－１,ｂｉｄ。用氨茶碱后各时间点静脉采血,测定茶碱血药浓度,用３Ｐ８７药动学软件计算参数,用ｔ检验进行统计,结果：单用氨茶碱与合用尼群地平的药时点静脉采血,测定茶碱血药浓度,用３Ｐ８７药动     

利巴韦林对兔体内氨茶碱药物动力学的影响

本文用紫外分光光度法测定了单用氨茶碱及合用利巴韦林后兔血清的茶碱浓度，结果表明：合用利巴韦林较单用氨茶碱Ｋ值增大，Ｔ１／２减小，ＣＬ增加，但经统计学处理无显著性差异（Ｐ＞０．０５），说明利巴韦林对兔体内氨茶碱的药物动力学无显著影响，两药可以合并使用     

氧氟沙星对人体内氨茶碱药物动力学的影响

本文采用荧光偏振免疫法测定8名健康志愿者单用氨茶碱和联合应用氧氟沙星后血药浓度的变化。结果表明,氧氟沙星对氮茶碱药动学参数有影响。其单用和联合应用氮茶碱的各药动学参数:半衰期T_(1/2)分别为7.79和10.14,峰浓度C_(max)分别为4.64和5.37,曲线下面积AUC 分别为56.37和100.5。经统计学处理有显著意义(P<0.05)。     

纳洛酮、氨茶碱对早产儿原发性呼吸暂停的疗效比较

目的：评估纳洛酮与氨茶碱两组方案治疗早产儿原发性呼吸暂停的疗效差异。方法：42例患儿随机分成纳洛酮治疗组20例、氨茶碱治疗组22例。结果：用药1h、1～24h、24～72h，两组治疗效果在统计学上有显著差异，72h后无统计差异。结论：用药72h内纳洛酮效果优于氨茶碱。     

Influence of simvastatin at high dose and nifedipine on hemodynamic parameters in rabbits

Recent findings in vitro have shown that statins could reduce cardiomyocyte viability. The correlation between statin cardiotoxicity, assessed in vitro, and cardiac efficiency, investigated in vivo has not been estimated so far. The aim of the present experiment was to establish the impact of high-dose simvastatin on the hemodynamic parameters, especially on myocardium efficiency, after continuous infusion of dopamine. Moreover, hemodynamic interaction between simvastatin and nifedipine, metabolized by the same izoenzyme CYP3A4 was examined. The experiments were performed on twenty seven New Zealand white rabbits. The animals were divided into four groups receiving: 0.2% methylcellulose (MC) (control group), nifedipine, simvastatin or simvastatin + nifedipine, for 14 days (p.o.). The following hemodynamic parameters were estimated: cardiac output index (COI), heart rate (HR), systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP) and total peripheral resistance index (TPRI). The registration of hemodynamic parameters was performed by Doppler method (Hugo Sachs Electronic Haemodyn). Dopamine did not cause a statistically significant increase in COI in rabbits receiving simvastatin alone or concomitantly with nifedipine. Nifedipine significantly lowered COI, BP and HR in rabbits if given simultaneously with simvastatin. In conclusion, administration of nifedipine may elicit detrimental impact on statin therapy, resulting in the worsening of cardiac performance. This may suggest another mechanism of drug-drug interaction than the one based on CYP3A4 inhibition.     

Pharmacokinetics of nifedipine after a single oral dose in patients with disorders of cerebral circulation

The pharmacokinetics of nifedipine was studied in 44 patients with disorders of cerebral circulation. A significant variability of the pharmacokinetic parameters in different patients was revealed. According to the results of the cluster-analysis, the main types (classes) of nifedipine pharmacokinetics were established and the possibility of regarding the patient examined as having this or that type during the measurement of the blood nifedipine concentration 2, 3 and 4 hours after administration of the drug was shown. The relationship between the type of nifedipine pharmacokinetics and its antiaggregatory effect was established.     

Effects of acute administration of nifedipine on glomerular filtration rate and urinary excretion of sodium and uric acid in patients with mild-moderate essential hypertension

A prospective study was conducted in 25 patients with essential hypertension to study the effects of sublingual administration of nifedipine on some renal functions. Glomerular filtration rate was estimated by radioisotope clearance techniques using Tc-99m diethylene triamine pentaacetic acid (DTPA). The change in urinary excretion of sodium and uric acid were also monitored. A basal estimation of these parameters was followed by repeat studies after lowering the blood pressure to normotensive levels by sublingual administration of nifedipine. It was observed that acute administration of nifedipine does not produce a significant change in the glomerular filtration rate, but causes marked and significant natriuresis and uricosuria.     

Effects of nifedipine on renin release and renal function in anesthetized dogs

The effects of nifedipine, classed as a calcium entry blocker, on urinary excretion and renin release were investigated in anesthetized dogs. Nifedipine was infused into one renal artery for three consecutive 10-min periods, at incremental rates of 0.3, 1, and 3 micrograms/min. Intrarenal infusion of nifedipine (3 micrograms/min) produced marked increases in urine flow rate (by 200%) and in urinary sodium (by 210%) and potassium (by 40%) excretion rates of the infused kidney without changes in mean systemic blood pressure, heart rate, glomerular filtration rate, and filtration fraction. Urinary osmolarity was slightly decreased by the drug, but this change was not statistically significant. There were no consistent changes in these parameters for the contralateral noninfused kidney. Renin secretion rate was increased to three times the preinfusion level during infusion of the highest nifedipine dose. The blood flow to the infused kidney was increased, and ipsilateral renal vascular resistance was simultaneously decreased upon nifedipine infusion. These results suggest that a nonhypotensive dose of nifedipine causes an increase in renin secretion and that this drug has a striking effect on the reabsorption of sodium and water by the renal tubules.     

Evaluation of the method for nifedipine administration for a rapid onset of clinical effect: a clinical study in normal volunteers

Nifedipine is frequently used for patients who require an immediate reduction of blood pressure elevated temporarily by various administration techniques including sublingual route without administrating intravenous infusion of vasodilator. A cross-over clinical study was conducted to investigate the optimal administration method of nifedipine for rapid management of hypertension. Four method of administering 10 mg nifedipine (the capsule was bitten and swallowed, sublingually with a hole in it or the contents administered orally or intranasally with a syringe) were evaluated with regarded efficacy, safety, and usefulness in 6 normal volunteers. Systolic and diastolic blood pressures were correlated with the nifedipine serum concentration in each method. Nifedipine pharmacokinetic parameters differed among the 4 administration methods. Nifedipine was absorbed rapidly by not only intestinal mucosa but also the nasal or oral mucosa. The pharmacological effect of intranasal or sublingual administration was superior. However, mint oil which is present in nifedipine capsules stimulates nasal mucosa when administered intranasally. For clinical usage, nifedipine capsules in which a hole is made with a needle, administered sublingually, can be effectively and safely used for rapid management of systemic hypertension.     

BRL 34915, a novel antihypertensive agent: comparison of effects on blood pressure and other haemodynamic parameters with those of nifedipine in animal models

The effects of BRL 34915, (+/-) 6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidyl)-2H-b enzo [b]-pyran-3-ol, on blood pressure and other haemodynamic parameters in animals have been investigated in comparison with those of nifedipine. In conscious spontaneously hypertensive rats and renal hypertensive cats and dogs the oral doses of BRL 34915 lowering blood pressure are 10 to 30 times lower than those of nifedipine. Tachycardia evoked by BRL 34915 tends to be less than that produced by nifedipine in the cat and of similar magnitude in the dog. The antihypertensive response to BRL 34915 in these models is reproducible on repeat once daily dosing without rebound hypertension on cessation of dosing. In studies using electromagnetic flow probes to measure regional blood flow in anaesthetised cats the intravenous administration of BRL 34915, unlike that of nifedipine, markedly increases renal blood flow yet BRL 34915 lacks the marked effect of nifedipine on femoral blood flow. BRL 34915, a compound structurally unrelated to existing cardiovascular drugs, is a potent new antihypertensive agent having an interesting profile of activity that renders this compound of clinical interest.