利多卡因和苯甲醇对人体肌注青霉素的药动学及生物利用度的影响

临床肌注青霉素常以注射用水作稀释溶媒,由于注射部位产生难以忍受的疼痛和硬块,目前多以2％苯甲醇代替注射用水使用。苯甲醇虽有一定的止痛作用,但引起注射部位产生硬结。1983年以来,我院使用0.25％利多卡因代替苯甲醇和注射用水作青霉素肌注溶媒,使用表明这种溶媒具无疼痛,不使局部产生硬块,病人乐于接受等优点。近来已有0.25％利多卡因作青霉素无痛溶媒的报道,体外实验证明利多卡因、苯甲醇对青霉素抑菌作用和注射用水无差别,对薄层层析试验影响也无差异,而刺激性和溶血作用以利多卡因为优。呼吁以0.25％利多卡因代替苯甲醇作无痛溶媒使用。但两者对青霉素肌注后的药动学及生物利用度影响如何这一临床评价却未见报道,本文将报道这一研究结果。     

氨苄青霉素的剂型和生物利用度研究

利用紫外分光光度法测定志愿者投药后尿中氨苄青霉素浓度,同时采用隔室模型和矩分析两种方法评价了氨苄青霉素的药物动力学和生物利用度。结果表明氨苄青霉素无水物和三水合物生物利用度无显著性差异;国产氨苄青霉素酞酯与母体比较,生物利用度提高不明显;各种口服制剂(胶囊,片剂和糖浆剂)尿中回收给药量百分率均无显著性差异;直肠给药吸收很快,但生物利用度低于口服给药,静滴给药80%以上以原型由尿中排出。     

八个牌号的氨苄青霉素胶囊的生物科用度比较

作者鉴于某些药学组织曾提出氨苄青霉素作为口服制剂存在不同的生物利用度问题,而在苏丹境内氨苄青霉素胶囊使用广泛,且市售的牌号甚多,故收集了八种牌号的氟苄青霉素胶囊(500mg),经健康志愿受试者口服,用化学方法测定尿药排泄量来比较其生物利用度。     

国产青霉素V钾胶囊剂的药代动力学和生物利用度

本文用青霉素V钾胶囊剂与进口青霉素V钾片剂进行人体药代动力学和生物利用度研究.选择12名健康男性志愿者,采用自身交叉对照试验方法,分别单剂量一次口服青霉素V钾500mg,青霉素V钾血药浓度用微生物法测定,以枯草芽孢杆菌(63501)作为检定菌.青霉素V钾血药浓度--时间数据用3p87程序进行自动拟合并求算药代动力学参数,用NDST程序对AUC、Tmax和Cmax的实测值作生物等效性检验.结果:口服青霉素V钾片剂和胶囊剂两种制剂后青霉素V钾药代动力学参数分别为:T1/2:31.27±11.12min,27.57±6.46min(P>0.05);Cmax:9.14±3.07mg·L-1,9.69±2.66mg·L-1(P>0.05).青霉素V钾的相对生物利用度为97.99%±13.44%.结论:青霉素V钾的AUC、Tmax和Cmax经配对t检验、双单侧t检验、方差分析表明国产青霉素V钾胶囊剂与进口青霉素V钾片剂为等效制剂.     

国产青霉素V钾颗粒剂的药动学及相对生物利用度

目的观察健康志愿者口服青霉素V钾颗粒剂的药动学及相对生物利用度。方法12名健康志愿者随机交叉口服等剂量青霉素V钾颗粒剂及青霉素V钾片剂(参比药),并用微生物法测定青霉素V钾的血药浓度。结果单剂量空腹口服500mg受试药与参比药后T     

青霉素V钾片在健康人体内的药动学和生物等效性

建立了LC-MS/MS法测定人血浆中青霉素V钾的浓度,并研究了20名健康志愿者单剂量随机交叉口服青霉素V钾片0.5g后的药动学和相对生物利用度。青霉素V钾受试制剂与参比制剂的主要药动学参数分别为AUC0-7h(9.61±3.94)和(9.69±4.52)μg·h·ml-1,AUC0-∞(9.72±3.96)和(9.79±4.51)μg·h·ml-1,cmax(8.36±4.14)和(8.47±4.47)μg/ml,tmax(0.53±0.15)和(0.54±0.14)h。受试制剂相对于参比制剂的生物利用度为99.3%,两制剂具有生物等效性。     

青霉素V钾健康人体药物动力学及相对生物利用度

以美国进口的青霉素 V钾片为标准参比制剂 ,研究国产青霉素 V钾片和胶囊在健康人体药物动力学及相对生物利用度。按 3制剂、3周期的 3× 3拉丁方试验设计 ,9名健康男性受试者 ,分别口服进口及国产青霉素 V钾 15 0 0 mg,采用微生物法测定血药浓度 ,用 3P87软件经微机处理药 -时数据。结果证明 ,进口及国产青霉素 V钾的体内过程均符合二房室模型 ,与标准参比制剂相比 ,两种被试制剂的 AUC、Cmax、Tmax均无显著差异 ,相对生物利用度分别为 10 2 .5 1± 11.0 9% (84.6 1%～ 114.49% )与 92 .5 0± 8.47% (82 .88%～10 6 .6 3% )。结论 :国产青霉素 V钾片和胶囊均具有生物等效性。     

N—酰基氨基酸增进鼠直肠对氨苄青霉素钠的吸收

氨苄青霉素钠以口服给药治疗感染性疾病,早就用于临床。然而,据报道它的生物利用度,在人体内仅达30～50%,其原因乃是其脂溶性低的缘故。最近,应用辅助药物改善吸收不良药物的生物利用度,特别是在直肠给药中,应用辅助药物引起了人们的极大兴趣。据报道,水杨酸酯、烯胺衍生物、羧酸衍生物、胆汁     

慢心利及类似口服抗心律失常药

治疗心律失常尤其是室性心律失常,对于避免突然死亡非常重要。一般首选利多卡因。但是口服的利多卡因从肠道吸收后,它经门静脉通过肝脏时在进入全身循环前大部分已发生代谢,其生物利用度非常低(低于30%),消除半衰期也较短(1～2小时)。故只限于短期静脉给药。因此希望出现能口服而副作用少的抗心律失常药。而慢心利是与利多卡因有同样电生理特点的口服抗心律失常药。     

氨苄青霉素的无水及三水合物的生物利用度的比较

氨苄青霉素有两种晶型,即无水化物及三水化物。它们具有不同的性质,如前者水溶性较大,溶解速率较高。本文以纯氨苄青霉素无水化物及三水化物的相同处方进行人体生物利用度的重新评价。10例健康男性受试者,年龄21～25岁,体重110～     

First-pass elimination of lidocaine in the rabbit after peroral and rectal route of administration

Lidocaine shows pronounced first-pass metabolism upon peroral administration in man (about 30 per cent peroral bioavailability). Since the rectal bioavailability is about 65 per cent in man it is assumed that some drug is directly absorbed into systemic circulation by-passing the liver. In rats peroral bioavailability is about 8 per cent whereas rectal bioavailability is about 100 per cent. This indicates that the rat is not a suitable model to study rectal lidocaine dosage forms. The purpose of this study was to investigate lidocaine disposition and bioavailability in rabbits after peroral and rectal administration. The peroral bioavailability in rabbits was found to be about 6 per cent and the rectal bioavailability is about 33 per cent. The results indicate that the rabbit is a suitable model for the study of systemic absorption of rectal lidocaine dosage forms.     

Comparison of the bioavailability of dexibuprofen administered alone or as part of racemic ibuprofen

Two bioavailability studies of S(+)-ibuprofen (dexibuprofen) were conducted in healthy volunteers to define the relationship between the bioavailability of the drug after administration of dexibuprofen alone or as part of ibuprofen racemate. Enantioselective plasma drug analysis was used throughout. In the first study, the bioavailability of dexibuprofen from a 400 mg tablet formulation was compared with that from 400 mg in aqueous solution.The tablet formulation did not influence the bioavailability of the drug and dexibuprofen was well absorbed from the gastro-intestinal tract.The second study was divided into three identical parts. Bioavailability of dexibuprofen 200, 400 and 600 mg was compared with its bioavailability from ibuprofen racemate 400, 800 and 1200 mg.The second study showed that the mean relative bioavailability of dexibuprofen to ibuprofen racemate was 0.66, thus enabling the estimation of clinically useful dexibuprofen doses from the usual doses of the racemate. The 95% confidence interval limits did not include 0.5, leading to the conclusion that administering half of the racemate dose would not provide patients with an adequate amount of therapeutically active drug.     

In vitro physiologically based extraction test (PBET) and bioaccessibility of arsenic and lead from various mine waste materials

In vivo models show that the bioavailability of soil contaminants varies between site and type of matrix. Studies demonstrated that assuming 100% bioavailability of arsenic (As) and lead (Pb) from soils and mine waste materials overestimates the risk associated with human exposure. In in vitro systems, the simulated bioavailability of a contaminant is referred to as the "bioaccessibility" and is used as an alternative quantitative indicator for in vivo derived bioavailability estimates. The general concept of the in vitro extraction test is to predict the bioavailability of inorganic substances from solid matrices by simulating the gastrointestinal tract (GIT) environment. The aims of this study were to: (1) investigate the bioaccessibility of As and Pb from various mine wastes, including tailings, heap leach, and waste rock, using a physiologically based extraction test (PBET); (2) validate the bioaccessibility values from PBET with in vivo bioavailability values measured using animal models; and (3) correlate PBET results with the bioavailability values measured from alternative in vivo models (rats and cattle, from Bruce, 2004). Significant correlation was observed between bioaccessibility values from PBET, and bioavailability values generated for both rats and cattle, demonstrating the potential to utilize PBET as a relatively inexpensive alternative to in vivo models for bioavailability assessment.     

Digoxin tablets--a review of the bioavailability problems.

A review is presented of the more significant aspects of recent bioavailability studies on digoxin tablets that have led to the identification of variations among commercially available tablets and of the correlation of the methods commonly used in such bioavailability evaluations. Pharmacopeial requirements for tablet-to-tablet uniformity of content do not automatically yield uniformity of bioavailability. In vitro dissolution rate of digoxin tablets generally has been shown to correlate with in vivo bioavailability, and this has led to new governmental and pharmacopeial requirements for digoxin tablets. However, some recent reports have shown that in vitro dissolution rate may not always correlate well with bioavailability. The relevance and significance of digoxin tablet bioavailability to clinical effects and therapeutics are briefly discussed.     

Evaluation of a novel method to estimate absolute bioavailability of drugs from oral data

The goal of this investigation was to evaluate the performance of a novel method allowing estimation of absolute bioavailability from oral data only. In contrast to the traditional method, which compares areas under the drug concentration time curves after oral and intravenous administration in subjects with normal renal function, the novel method uses total and renal clearance values following oral administration from subjects with varying renal functions to estimate bioavailability. The novel method can also provide estimates for nonrenal clearance.Published data on total clearance and renal clearance of drugs obtained from subjects with variable renal functions were collected, the novel method applied, estimates of bioavailability and nonrenal clearance obtained and compared with reported estimates by the traditional methods. In addition computations were performed to assess various factors that could possibly affect the reliability of the novel method. The results indicated that the novel method provides accurate estimates for bioavailability of drugs meeting the prerequisites: linear kinetics, predominant renal excretion in normals, absence of metabolic polymorphism and independence of bioavailability and nonrenal clearance from renal function. The average (standard deviation) of the prediction error and bias of the bioavailability estimates by the novel method was 7.8 (6.0) and -1.4 (9.8)%, respectively. The estimates for nonrenal clearance by the novel method were less accurate. The computations confirmed that the estimates by the novel method are sensitive to renal-function dependent changes in nonrenal clearance and bioavailability and also depend on the extent of renal excretion of a drug. In conclusion, the novel method's main use is to diagnose absence or presence of changes in bioavailability and non-renal clearance of drugs in populations with varying renal function.     

Dissolution systems for chloramphenicol tablet bioavailability.

The relationship between chloramphenicol (I) tablet bioavailability and in vitro dissolution rates was examined. The effect of solid food on the I tablet and powder bioavailability was also studied. Five tablets of I were selected for bioavailability testing on the basis of the dissolution rates of 18 I tablets (250 mg) determined by several methods. Compound I, 500 mg, was administered orally to five subjects, following overnight fasting, according to a crossover design. The bioavailability parameters were obtained from urinary I excretion. Among the five formulations studied, only one tablet (F) showed significantly poorer bioavailability. The dissolution rates at pH 1.2 did not give the same rank order as the bioavailability. The dissolution rate of Tablet F showed remarkable pH dependency. The dissolution rates at pH 4 showed good correlation with in vivo bioavailability data. The bioavailability of I powder was not affected by solid food. Tablet F, which had poor bioavailability in the fasting state, showed good bioavailability when administered just after the standard breakfast.     

Factors affecting the bioavailability of phenytoin

The bioavailability of seven phenytoin (DPH) formulations, five brands of tablets and two suspensions, was measured in a cross-over study with six healthy volunteers. Single doses of 600 mg of DPH were used and the bioavailability was determined as the area under the serum DPH concentration-time curve (AUC). Highly significant differences between the bioavailability of various products were found. The highest bioavailability was obtained with suspension prepared from the micronized raw material of DPH and the lowest bioavailability (26% of that of the former suspension) with the tablets having the largest particle size of DPH. The in vitro dissolution rate of the products in borate buffer at pH 9 showed a significant (p less than 0.01; r=0.93) correlation with the in vivo bioavailability of the DPH products. In addition to the particle size, several other formulation factors are important for dissolution rate and absorption characteristics of DPH products. The properly performed measurement of the in vitro dissolution rate can be used as a preliminary screening test in predicting the bioavailability of DPH products.     

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。     

Bioavailability of propranolol following oral and transdermal administration in rabbits

The systemic bioavailability of propranolol was evaluated following oral and transdermal administration in rabbits. Using a four-way crossover study, the bioavailability of propranolol following oral administration was determined to be 12.3 +/- 5.9%, indicating that propranolol is subject to extensive hepatic first-pass metabolism in rabbits. Transdermal delivery of propranolol, via an adhesive delivery device, resulted in a bioavailability of 74.8 +/- 10.1%, indicating that the transdermal delivery of propranolol can significantly increase systemic bioavailability over oral administration. Skin irritation studies indicated that neither propranolol nor the adhesive used in the device caused any appreciable skin irritation.