The bioavailability in man of marketed brands of chlorpropamide

Summary A specific TLC assay procedure has been used to compare the bioavailability of three brands of chlorpropamide, Diabetasi, Diabinese, and Prodiaben. Serum concentrations of drug were determined at various times after administration of single oral doses to normal volunteers in a crossover study. Prodiaben gave significantly lower serum levels than the other two brands during the first 24 h after dosing.     

尼莫地平片的溶出度和生物利用度的相关性研究

分别用部颁试标、部颁正标和以人工肠液为溶出介质的浆法测得尼莫地平片的溶出度,分别与其体内的生物利用度进行相关性研究。结果表明,按部颁试标测定的溶出度与生物利用度呈无显著性负相关,按部颁正标测定的溶出度与生物利用度呈无显著性正相关,而若采用人工肠液为溶出介质,则所得溶出度与生物利用度呈显著的正相关,即采用人工肠液为溶出介质最为合理。     

扑热息痛直肠胶囊剂的溶出度和生物利用度研究

作者制备的扑热息痛直肠囊剂，可根据小儿体重分装成不同规格，便于临床实现个体化给药。本品与市售剂在家兔体内的达峰时分别为１．８７，１．６７ｈ；峰浓度及ＡＵＣ分别为５４．８６，４６．０９（ｍｇ／Ｌ）和１９８．９４，１８８．９４（ｍｇ．ｈ．Ｌ）。直肠胶囊剂用自行设计的“转筒膜法”测定，体外累积溶出百分率与体内吸收百分率间有显著相关性。     

Effects of aqueous solubility and dissolution characteristics on oral bioavailability of entacapone

Entacapone is a new catechol‐O‐methyltransferase (COMT) inhibitor used clinically in a triple combination therapy for Parkinson's disease (PD). The bioavailability of entacapone after oral administration is low and subject to large interindividual variation. The purpose of this study was to evaluate aqueous solubility/dissolution profiles of entacapone in vitro, and to evaluate their role in the poor oral bioavailability of entacapone in rats. The effect of the novel pharmaceutical excipient hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) on the aqueous solubility and dissolution of entacapone, and on entacapone bioavailability in rats, was also studied. The aqueous solubility of entacapone determined in this study is below 80 μg/ml at pH ≤5.0 and increases with increased pH. Due to its poor aqueous solubility, the dissolution of entacapone in an acidic environment is very slow. Complexation of entacapone with HP‐β‐CD (10% [w/v]) increases the aqueous solubility of entacapone 12‐fold and 85‐fold at pH 3.0 and at pH 5.0, respectively, and improves its bioavailability at the former pH about 2‐fold, compared to an entacapone suspension at that pH. The administration of entacapone as a pH 7.4 solution further increases the absolute bioavailability of entacapone, which is 1.8 and 3.3 times higher compared to the inclusion complex or suspension, respectively. In conclusion, it is possible to increase entacapone's bioavailability by improving its solubility and dissolution properties. However, the solubility and dissolution properties of entacapone do not fully explain its erratic bioavailability. Drug Dev. Res. 49:238–244, 2000. © 2000 Wiley‐Liss, Inc.     

Relative bioavailability of acetazolamide tablets

Plasma acetazolamide concentrations were determined enzymatically after administration of three tablet dosage forms and a reference solution to 12 human subjects in a crossover study. Two of the tablet products represented different lots from the same manufacturer. There were no significant differences in area under the plasma level-time curves among the four treatments. However, significant differences were found among tablets in terms of peak plasma concentration and time to reach peak concentration. These apparent differences in rate of absorption were correlated with in vitro dissolution data obtained in pH 1.5 dissolution medium.     

Plasma concentrations and relative bioavailability of naftidrofuryl from different salt forms

The relative bioavailability of the vasodilator naftidrofuryl from formulations containing its oxalate or citrate salt has been estimated using a specific HPLC assay, and a less specific fluorimetric assay, to measure plasma drug concentrations. The conclusions of the study were the same irrespective of the assay employed. The relative rate, but not the extent, of bioavailability of naftidrofuryl from the citrate salt (peak 1096 ng ml-1 at 0.76 h) was marginally greater (p = 0.003) than that from the oxalate salt (peak 922 ng ml-1 at 0.94 h). The degree of intersubject variability was similar after administration of either salt form. The mean half-life of naftidrofuryl was 1.8 h and its mean residence time was 2.5 h.     

Comparison of the bioavailability of two slow release preparations of disopyramide

Summary The bioavailability of two slow release preparations of disopyramide has been compared in a randomized cross-over trial of Rythmodan L. A. 250 mg b. d. and Dirytmin Durettes 300 mg b. d., given to 10 healthy volunteers. The plasma concentrations of disopyramide were measured on the 5th day of each treatment period.With both preparations, plasma concentrations were well sustained. The amount absorbed was slightly lower after Rythmodan L. A. than after Dirytmin Durettes, but the fluctuations over a dosing interval were significantly more pronounced for Dirytmin Durettes than for Rythmodan L. A.     

A new statistical procedure for testing equivalence in two-group comparative bioavailability trials

The clinical problem of testing for equivalence in comparative bioavailability trials is restated in terms of the proper statistical hypotheses. A simple t-test procedure for these hypotheses has been devloped that is more powerful than the methods based on usual (shortest) and symmetric confidence intervals. In this note, this new procedure is explained and an example is given, including the method for sample size determination.     

格列齐特片在健康人体内的相对生物利用度

目的研究格列齐特片在健康人体内的相对生物利用度 ,评价两种格列齐特片剂的生物等效性。方法10名健康受试者口服格列齐特受试片和参比片后 ,采用高效液相色谱法测定血药浓度 ,SCIENTIS程序拟合药代动力学参数 ,t检验比较组间差异 ,双单侧检验评价生物等效性。结果格列齐特血药浓度—时间曲线符合单室开放模型 ,受试片和参比片的达峰时间Tmax 分别为(4.272±0.631)h和(4.031±0.574)h ,达峰浓度C max 为(7.497±0.935)μg·ml -1和(7.408±1.171)μg·ml-1 ,曲线下面积AUC为(104.986±27.523)μg·h·ml-1 和(108.232±22.437)μg·h·ml-1,两组间均无显著性差异(P>0.05)。结论格列齐特受试片的相对生物利用度为96 679 % ,格列齐特受试片与参比片具有生物等效性。     

头孢拉定胶囊溶出度、体内生物利用度及其相关性研究

本文对不同厂家头孢拉定胶囊溶出度、体内生物利用度进行了比较试验,表明头孢拉定胶囊的处方、工艺、辅料、空胶囊对于头孢拉定溶出度、生物利用均有影响,体外溶出度与体内生物利用度有一定的相关性。     

固体分散法增加对乙酰氨基酚生物利用度的研究

用固体分散技术可显著增加难溶性药物对乙酰氨基酚的溶出速率，选择尿素为载体，将对乙酰氨基酚制成固体分散体，进而制成片剂和栓剂，与市售片和市售栓比较，溶出速率加快，生物利用度明显提高。     

不同载体对缬沙坦纳米骨架载药系统溶出行为和生物利用度影响的研究

目的 通过调节纳米骨架载药系统（NDDS）中载体类型和比例实现对缬沙坦体外溶出和体内生物利用度的调控。方法 以缬沙坦作为模型药物,分别选取酸性敏感材料Eudragit E100（E100）、碱性敏感材料Eudragit L100-55（L100-55）作为载体材料,介孔二氧化硅Sylysia 350（S350）、Aerosil 200（A200）作为纳米骨架,通过调节载体和骨架材料的类型和比例筛选出具有pH 1.2、6.8敏感释放行为的纳米骨架载体处方,考察缬沙坦在pH 1.2、6.8环境中释放和在大鼠体内的药动学行为特征。结果 筛选的pH 1.2敏感释放缬沙坦NDDS处方缬沙坦、S350、E100比例为1∶3∶1,pH 6.8敏感释放缬沙坦NDDS处方为缬沙坦、A200、L100-55比例为1∶1∶3。pH 6.8敏感释放处方可调控缬沙坦在肠道pH 6.8条件下特异性溶出;pH 1.2敏感释放处方在保持缬沙坦在pH 6.8高溶出特性的同时可特异性地提高胃部酸性条件下的药物释放。pH 1.2、6.8敏感释放缬沙坦NDDS均一定程度上改善了缬沙坦的生物利用度,其中pH 6.8敏感释放缬沙坦NDDS提高生物利用度的幅度更高,血药浓度变化比较平缓。结论 NDDS可以调控缬沙坦的体外溶出和生物利用度,有望应用于pH值敏感性难溶药物的递送。     

Plasma concentrations and bioavailability of isosorbide dinitrate and pindolol from a combination formulation

The plasma concentrations and bioavailability of sustained-release isosorbide denigrate and standard-release pindolol have been compared after administration of these drugs in combination and alone. Bioavailability parameters of isosorbide dinitrate and pindolol obtained after administration of the drugs in combination were not significantly different (P>0.05) to those obtained after administration of either drug alone. Two peaks of mean concentrations of isosorbide dinitrate occurred in plasma after administration of 30 mg of this drug in combination with 7.5 mg pindolol (4.4 ng ml^?1 at 1 h and 4.5ng ml^?1 at 5h), or alone (5.9ngml^?1 at 2h and 5.7ng ml^?1 at 5h). In each case, plasma concentrations of isosorbide dinitrate were maintained during at least 8 h, whereas the drug was not detected in plasma at 2.5 h after administration of a standardrelease formulation. The peaks of mean concentrations of pindolol were 39.7ng ml^?1 at l.5h after administration of 7.5 mg drug in combination with isosorbide dinitrate and 38.0 ng ml^?1 at 1 h after administration of the drug alone. Concentrations of pindolol in plasma declined with a half-life of 3 h.     

阿普洛韦片在人体内的相对生物利用度和生物等效性

目的;比较两种阿昔洛韦片剂的相对生物利用度及生物等效性.方法:8例男性健康受试者自身交叉对照、草剂量Po阿昔洛韦受试片或参比片各400mg.采用HPLC法测定血浆阿昔洛韦浓度、单室模型拟合药物动力学参数,数据经对数转换后进行双单侧检验评价生物等效性.结果:阿昔洛韦受试片和参比片的t_max、c_max、AUC相比较,P均>0.05,阿昔洛韦受试片的相对生物利用度为(104.49土18.06)%.结论:阿昔洛韦受试片和参比片生物等效.     

提高难溶性药物尼群地平溶出率和口服生物利用度的研究

目的通过制剂手段提高难溶性药物尼群地平的体外溶出率和家犬体内的相对生物利用度。方法用共研磨法制备研磨混合物,并用差热分析法、X射线衍射法、显微镜法鉴别药物在共研磨混合物中的存在状态,在此基础上采用直接压片法制备口腔速崩片,测定体外溶出速率,所有试验均以物理混合物为参照进行比较;用HPLC法测定3只健康家犬分别口服尼群地平口腔速崩片(受试制剂)、市售普通片(参比制剂)后不同时间血浆中尼群地平的浓度,计算药物代谢动力学参数及相对生物利用度。结果共研磨混合物中尼群地平的粒径远小于物理混合物,并以微晶状态存在;以共研磨混合物制备的口腔速崩片的溶出速度和程度均大于以物理混合物制备的口腔速崩片;在家犬体内受试制剂和参比制剂的tmax分别为1.5 h和4.25 h,ρmax分别为176.54μg.L-1和111.12μg.L-1,AUC0-t分别为903.78μg.h.L-1和651.99μg.h.L-1,AUC0-∞分别为1 030.46μg.h.L-1和903.68μg.h.L-1,受试制剂的相对生物利用度为138.5%;受试制剂的体内吸收和体外溶出速率均高于参比制剂。结论通过制备共研磨混合物和口腔速崩片的方法,提高了尼群地平的体外溶出度和家犬体内的相对生物利用度。     

对乙酰氨基酚栓剂人体相对生物利用度和生物等效性

目的:研究进口试验制剂与国产对乙酰氨基酚栓剂(参比制剂)的相对生物利用度和生物等效性.方法:采用HPLC法测定18例健康男性志愿者单次交叉直肠给予参比制剂2粒(300mg)及试验制剂2粒(250mg)后的血药浓度,经CRFB软件处理,计算其药动学参数和相对生物利用度,评价两制剂的生物等效性.结果:试验制剂和参比制剂的t1/2分别为(3.94±1.54)和(3.81±1.24)h;Tmax分别为(1.56±0.57)和(1.58±0.43)h;平均滞留时间MRT0～tn分别为(5.67±1.44)和(5.40±1.28)h;Cmax分别为(1.73±0.38)和(1.61±0.34)μg·mL-1;AUC0～tn分别为(8.01±2.20)和(7.54±1.82)μg·h·mL-1.试验品与参比品的相对生物利用度为(109.07±27.92)%,经统计学处理,试验品AUC0～t的90%置信区间为97.20%～115.85%,Cmax的90%置信区间为98.64%～116.97%.结论:两制剂生物等效.     

司帕沙星片剂在健康人体的药动学和相对生物利用度

目的建立测定血浆中司帕沙星的HPLC内标法并研究司帕沙星片的相对生物利用度及生物等效性。方法 20名健康志愿者分两组,随机、交叉口服受试制剂与参比制剂的司帕沙星片0.4 g,HPLC法测定血药浓度,计算药动学参数及生物等效性评价。结果受试制剂与参比制剂血浆中司帕沙星的tmax为(4.68±0.44)和(4.55±0.51)h;Cmax为(1 560.4±243.9)和(1 584.1±273.9)ng/ml;t1/2为(20.92±4.85)和(19.81±3.75)h;用梯形法计算AUC0-t为(43 325±12 174)和(44 139±11 815)ng.h/ml;AUC0-∞为(45 452±12 884)和(45 999±12 629)ng.h/ml。以AUC0-t计算,受试制剂的平均相对生物利用度为(97.9±5.8)%。结论两制剂具有生物等效性。     

Effect of antacids on aspirin dissolution and bioavailability

The in vitrodissolution profile, in vitroand in vivobuffering characteristics, and single-dose bioavailability of various buffered aspirin tablet formulations were studied. Buffering agents,such as magnesium and aluminum hydroxides (formulations B and C) or magnesium carbonate and aluminum glycinate (formulation D), significantly increased the rate of aspirin dissolution from solid dosage forms as compared to an unbuffered tablet (formulation A). The extent of aspirin absorption was equivalent with all formulations;however, the faster rate of dissolution (t₅₀ and t₉₀)with buffered formulations resulted in earlier and higher peak concentration of salicylate compared to that with unbuffered formulation, following a two-tablet dose in the fasting state. A comparison of the in vivobuffer capacity of a four-tablet dose of formulations B and D was performed in the postcibal state at the time of maximal meal-induced acid secretion, using a radiotelemetry procedure for determination of pH. Formulation B prolonged the interval of elevation of intragastric pH > 3 for 32 min as compared to 12 min for D.     

乳腺康口服液相对生物利用度及生物等效性研究

目的:评价乳腺康口服液和注射液在家兔体内生物等效性。方法:采用紫外分光光度法测定血药浓度。结果:乳腺康口服液和注射液的Tmax分别为(3.8065±1.009)h和(1.0809±0.59)h,Cmax为(0.5333±0.03)和(0.5328±0.16)mg/ml,AUC为(3.1095±0.9)和(2.8938±0.14)mg/ml,t1/2为(3.1035±1.0143)和(2.8720±0.93)h,乳腺康口服液相对生物利用度为106.1%。结论:经统计学分析,乳腺康口服液和注射液具有生物等效性。     

药物制剂人体生物利用度研究的若干问题

为获得较为理想、可靠的人体试验研究结果介绍药物制剂人体生物利用度研究中涉及到的一些具体实际问题，包括受试者的选择、试验条件均衡性的控制、药物动力学分析、生物利用度计算和生物等效性评价等．