时辰药物动力学

所有生物均受昼夜及季节性节律的影响 ,节律性是生命活动的基本特征。早在 1 9世纪 ,提出一个药物的服药时间对其治疗作用很重要 ,但除皮质激素治疗外 ,很少被人注意 [1]。近 2 0 a很多研究证明 ,人体的许多生理功能如心输出量、胃酸的分泌、血浆蛋白量、肝药酶的活性、尿和胆汁的排泄等均存在明显的昼夜节律 (circadian rhythm) ,因而不同时间服药可能产生不同的吸收、分布、代谢和排泄过程 ,导致许多药物的一种或多种药物动力学参数的变化 [2 ,3]。这就形成了药物动力学的一个新分支“时辰药物动力学 (chronopharmacokinetics)”。时辰药…     

布洛芬颗粒剂在大鼠体内的时辰药物动力学

在各种生物节律中，体温的昼夜节律是发现得较早、研究得较为深入的一种。与睡眠一觉醒及其他一些生理节律相比，体温昼夜节律的周期和相位都较为稳定，所以常以体温及其昼夜节律作为机体机能状态、疾病状态、治疗效应等的时问生物学指标”。布洛芬是一种疗效确切、毒副作用小、安全性高的非甾体抗炎镇痛药，临床应用广泛。至今尚未见有关布洛芬的时间药理学研究报道。本文初步研究了布洛芬颗粒剂对大鼠正常体温降低作用、     

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     

普罗帕酮对氨茶碱药物动力学的影响

本实验采用自身对照法观察氨茶碱、氨茶碱和普罗帕酮（Propafenose,心律平）占用后血清茶碱浓度的变化，按一室模型公式求算茶碱的有关药动学参数．实验结果表明：两药合用，茶碱的肌体清除率降低25％、半衰期延长，清除速率减慢（P＜0．05）．而茶碱的吸收和分布没有明显变化（Ka、Auc，P＞0．05）。     

中毒剂量氨茶碱在大鼠的时辰药物代谢动力学

中毒剂量氨茶碱在大鼠的时辰药物代谢动力学曾照宏，郑青山，栾家杰，丁学庭，宋寅生（皖南医学院弋矶山医院临床药学研究室，芜湖２４１００１）２０只大鼠在标准的明暗周期（明期：暗期＝１２：１２ｈ）下饲养１ｗｋ，自由进食进水，并随机分为２组。９：００组于上午９...     

复方雷尼替丁分散片在Beagle犬体内的时辰药物动力学

目的对Beagle犬早、晚服用复方雷尼替丁分散片后,探讨其血药浓度及药物动力学参数的时辰变化规律,为制定给药方案提供参考。方法采用RP-HPLC法,测定6只Beagle犬于早、晚分别给予复方雷尼替丁分散片后不同时间的血药浓度,将计算得到的药物动力学参数进行统计分析。结果雷尼替丁血药浓度在Beagle犬体内存在明显的节律性,早上给药组的药时曲线下面积(AUC)和达峰浓度(ρmax)均高于晚上给药组(P<0.05),其他药物动力学参数没有显著性差异(P>0.05)。结论雷尼替丁在Beagle犬体内血药浓度随着昼夜更替呈现节律性变化。     

左旋氧氟沙星对氨茶碱药物动力学的影响

采用荧光偏振免疫分析法(FPIA),在7名志愿者身上,对氨茶碱单用及与左旋氧氟沙星合用后,血中氨茶碱浓度的变化进行观测.结果表明,合用左旋氯氟沙星后氨茶碱消除速率常数k降低13.6%,清除率CL下降15.6%,半衰期T_1/2延长16.5%(P<0.05),但对峰浓度C_(max)、曲线线下面积AUC,表观分布容积V_d无显著影响(P相似文献   

顺铂在家兔体内的时间药动学

目的　研究顺铂在家兔体内药代动力学的时间节律特征。方法　实验动物饲养在标准环境中,分别于昼夜不同时辰一次给药,以原子吸收光谱法测定给药后不同时刻血中铂浓度,并将通过３ Ｐ８７ 程序计算所得的主要药动学参数按平均余弦法进行处理。结果和结论　顺铂的主要药动学参数呈一定昼夜变化,其中消除相半衰期（ Ｔ１２ β） 、表观分布容积（ Ｖｄ） 、曲线下面积（ Ａ Ｕ Ｃ） 、清除率（ Ｃ Ｌ） 等波动较大,峰、谷值之间具显著或非常显著差异。上述各参数昼夜节律峰值期分别在０２ ：１３ 、０４ ：４５ 、００ ：３７ 和１３ ：１０     

Chronopharmacokinetics and calcium in the prevention of gentamicin-induced nephrotoxicity in rabbits

The study used 36 New Zealand white rabbits organized into three groups of 12 animals each. Group I received gentamicin; Group II received joint administration of gentamicin and calcium chloride and Group III received gentamicin, calcium chloride and verapamil. All the drugs were administered over 16 day periods. Groups I and II were divided in two subgroups, one subgroup receiving the treatment in winter and the other in summer. The results obtained for Group I indicate that there is an influence of the seasonal period on the gentamicin elimination and/or distribution. Mean plasma levels of the antibiotic at steady-state as well as the amounts of gentamicin accumulated in renal tissue are higher in winter than in summer. On the other hand, when calcium was administrated with the antibiotic, no significant circannual variations were observed in the renal toxicity of gentamicin. Under our study conditions the presence of calcium diminishes gentamicin plasma levels and the amount accumulated in kidney. Calcium, probably, generated a diminution in renal damage and consequently gentamicin renal excretion increases. The differences between Group II and Group III are due to the effect of verapamil. This agent blocks the calcium channels reducing the calcium protective effect on the nephrotoxicity of gentamicin. © 1998 John Wiley & Sons, Ltd.     

Chronopharmacokinetics of doxorubicin in patients with breast cancer

Summary The chronopharmacokinetics of doxorubicin (DOX) has been studied in 18 patients suffering from breast cancer. They received combined chemotherapy, including DOX (50 mg/m² as an iv bolus), given at two different times (09.00 h or 21.00 h). The two randomized courses of the protocol were given to each patient at a four week interval.The total body clearance (CL) of DOX was significantly decreased when the drug was administered at 21.00 h, resulting in a longer elimination half-life and an increase in AUC. The renal clearance of DOX did not differ at the different times of administration, and it appears that the decrease in CL was related to a change in hepatic blood flow. The volume of distribution of the drug was not changed.     

渗透压微泵恒速给药丙戊酸在小鼠体内的时间药物动力学

以渗透压微泵植入小鼠皮下恒速给予丙戊酸钠，在达到理论稳态浓度时间后，血浆药浓呈昼夜变化，白昼高于夜间，峰值位于明期末。药动学研究揭示丙戊酸血药浓度的昼夜差异可能与其清除率及分布容积的昼夜变化有关。     

罗红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只新西兰白兔灌服罗红霉素前后对氨茶碱稳态血药浓度及药代动力学的影响。方法　实验分二期 :Ⅰ期为d 1～ 4单独灌服氨茶碱至稳态 ;Ⅱ期为d 5～ 10合用罗红霉素与氨茶碱 ,血药浓度采用HPLC法测定。结果　各期测得氨茶碱药代动力学参数 ,与Ⅰ期比较 ,Ⅱ期的AUC、CL/Fs、Ka、Ke、T1/ 2 (ka) 、Tmax差异有显著性 (P <0 0 5 ,P <0 0 1) ,而Cmax、V/Fc、T1/ 2 (ke) 在两期间差异均无显著性(P >0 0 5 )。结论　长期合用罗红霉素和氨茶碱 ,罗红霉素能延缓氨茶碱在兔体内稳态时的吸收和消除 ,提示合并用药时应对氨茶碱进行临床给药监测。     

Individualized aminophylline therapy in patients with obstructive airway disease: Oral dosage prediction from an intravenous test dose

Summary Theophylline disposition after an intravenous test dose of aminophylline was determined in 83 subjects: 7 patients with and 58 without congestive heart failure (CHF), and 18 healthy controls. Based on the pharmacokinetics of theophylline in the individual, the oral dosage of aminophylline was scheduled to attain steady-state trough theophylline concentrations (C_pred) near the therapeutic margin. Significant differences in theophylline clearance with a relatively constant volume of distribution were observed between various groups divided by age, smoking habit and CHF; the significantly different (p<0.001) mean clearance values were: 0.042±0.0161/h/kg (mean ± SD) in patients without CHF (n=58) as opposed to 0.016±0.001 l/h/kg in patients with CHF(n=7), 0.038±0.013 l/h/kg in non-smokers (n=59) versus 0.054±0.015 l/h/kg in smoking subjects (n=17), and 0.030±0.010 l/h/kg in elderly (>60 years) non-smoking patients (n=7) versus 0.057±0.017 l/h/kg in smoking patients (n=5) aged 40 to 59 years. No gender-related difference was detected in theophylline disposition. For all subjects together (n=83), there was no significant correlation between age and clearance (r=-0.111, p>0.1). The multivariate analysis indicated that the overall variability in theophylline clearance was affected first by the smoking habit (t=4.960; p<0.001) and second by CHF (t=-3.052; p<0.001), but not by age (t=1.140) or by sex (t=0.069). 78% of the patients who did not have CHF required a daily dose of aminophylline of 600 to 900 mg, whereas a dose of 300 to 450 mg was the rule in patients with CHF. The measured steady-state minimum concentration (C_meas) ranged from 5.4 to 14.6 µg/ml (9.0±2.2 µg/ml: mean ± SD) which was in good agreement with the C_pred (5.6 to 13.6, 9.0±1.6 µg/ml) in all patients (n=60) who received the oral dose of aminophylline calculated from the test dose. The overall prediction error was -0.08±1.83 µg/ml (–1.42±19.90%); only 3 of 60 measurements were found to be outside±2 SD. It is concluded that using a test dose to individualize aminophylline therapy is likely to remain the most reliable means to assure the maximum therapeutic benefit in patients with airway obstruction.A preliminary account of this study was presented at the Eighth International Congress of Pharmacology, Tokyo, July 19–24, 1981     

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。     

气相色谱法测定氨茶碱及其制剂中乙二胺的含量

目的:建立氨茶碱及其制剂中乙二胺的含量测定方法。方法:采用气相色谱法,用DB-624毛细管气相色谱柱(30 m×0.53 mm,3.0μm),程序升温(120℃保持7 min,以80℃.min-1上升至250℃,保持5 min),进样口温度180℃,检测器为FID,检测器温度250℃,内标为甲基异丙基酮。结果:乙二胺的线性范围为0.1193～0.5964 mg.mL-1(r=0.9995),理论板数大于10000,各相邻峰分离度均大于1.8,精密度、回收率的RSD均小于2.0%。结论:方法简单、准确,灵敏度高,重复性好,适用于氨茶碱及其制剂中乙二胺含量的测定。     

氨茶碱注射液在4种输液中的稳定性考察

本实验选择４种输液与氨茶碱注射液进行配伍。模拟临床使用浓度，分别在２５℃、３７℃时观察配伍药液从０～２４ｈ的外观性状、ｐＨ值、紫外光谱的改变及经时含量变化情况，经果表明：氨茶碱与０．９％氯化钠注射液配伍稳定，２４ｈ内外观、ｐＨ值、紫外光谱及含量基本不变，配伍静滴可行；与葡萄糖氯化钠、５％葡萄糖、１０％葡萄糖注射液配伍药液ｐＨ值略有下降、１２ｈ以后色泽有所加深，但２４ｈ内紫外光谱及含量基本未变，配伍静滴宜掌握在１２ｈ内用完，以上两种温度下结果基本一致。