The bio-availability of beta-acetyldigoxine alone and combined with aluminum hydroxide and magnesium hydroxide (Alucol)

The bio-availability of Novodigal (beta-acetyldigoxine) alone and applied together with Alucol (aluminum hydroxide, magnesium hydroxide) was studied in six healthy probands. Bio-availability parameters were calculated from the areas under the plasma concentration curves and from the comparison of the blood levels after absorption during steady state. There was no significant difference between the bio-availability of beta-acetyldigoxine alone and that of the combination with Alucol. Thus, beta-acetyldigoxine combined with antacids of the aluminum hydroxide and magnesium hydroxide type can be applied in the same dosage as usual since no decrease of effect has to be apprehended.     

Evaluation of buffering capacity and acid neutralizing-pH time profile of antacids

The antacid properties of seven antacids listed in the hospital formulary of a medical center were evaluated with in vitro tests. These included not only the preliminary antacid test and acid-neutralizing capacity test as described in the United States Pharmacopeia (USP XXIII), but also a buffering pH profile test. The preliminary antacid test measured the final pH of a 10-mL solution of 0.5 N HCl 10 minutes after addition of the minimum recommended dose of an antacid, while the neutralizing capacity test measured the amount (mEq) of HCl neutralized by the minimum recommended dose in 15 minutes. The buffering pH profile recorded the pH time course of dynamic simulated gastric fluid neutralization by a dose of an antacid. In the preliminary antacid test, magnesium oxide showed the highest pH (9.52 +/- 0.14, mean +/- standard deviation, n = 3); aluminum phosphate gel yielded a final pH of 2.51 +/- 0.01, thus failing to meet the criteria of an antacid (pH > 3.5). In the acid-neutralizing capacity test, hydrotalcite had the highest neutralizing capacity (28.26 +/- 0.3 mEq), while sodium bicarbonate had the lowest (7.40 +/- 0.12 mEq). In the buffering pH profile test, aluminum-magnesium hydroxide suspensions and hydrotalcite tablets maintained a steady optimum pH (3-5) for around 1.5 hours. One tablet of calcium carbonate, sodium bicarbonate or magnesium oxide could not raise the gastric pH to above 3, but two tablets increased the pH excessively (5.3 to 8.6). The higher dose (two tablets) of aluminum hydroxide hexitol complex could not raise the pH to the optimal level. These findings demonstrate that there is disparity in the antacid effectiveness estimated by the neutralizing capacity test and the buffering pH profile test and suggest that the efficacy of an antacid cannot be accurately predicted from its acid-neutralizing capacity. The dose of antacids greatly influences the neutralizing pH profiles. Aluminum-magnesium compounds appear to provide steadier buffering than carbonate compounds or magnesium oxide.     

Ondansetron absorption in adults: effect of dosage form, food, and antacids

Ondansetron is a competitive serotonin 5-HT3 receptor blocker that has proved useful in the prevention of emesis due to cisplatin and other cancer chemotherapeutic agents. In a randomized, open-label, crossover study in 24 healthy male subjects, the relative bioavailability of a single 8-mg tablet was compared with that of an 8-mg solution using the two one-sided t-tests. The tablet and solution formulations were bioequivalent, as confirmed by similarities in mean Cmax (26.3 vs 27.7 ng/mL), Tmax (1.79 vs 1.70 h), and AUC (166.0 vs 167.3 ng.h/mL) values. In another randomized, open-label, crossover study in 12 healthy male subjects, the bioavailability of an 8-mg ondansetron tablet administered 5 min after a standard meal was slightly but significantly greater than in fasted subjects, as indicated by comparative mean AUC values [201.4 ng.h/mL (fed) vs 172.5 ng.h/mL (fasted)]. Coadministration of a magnesium hydroxide/aluminum hydroxide antacid did not affect the bioavailability of the ondansetron tablet.     

Effect of aluminum hydroxide/magnesium hydroxide antacid and bismuth subsalicylate on gastric pH in horses

OBJECTIVE: To assess the effect of aluminum hydroxide/magnesium hydroxide antacid and bismuth subsalicylate on gastric pH in clinically normal horses and to develop guidelines on the use of these agents for treatment of peptic ulcer disease in horses. DESIGN: Prospective, randomized, controlled trial. ANIMALS: 5 clinically normal adult horses with chronically implanted gastric cannulas. PROCEDURE: Each horse received all 5 treatments (30 g of aluminum hydroxide/15 g of magnesium hydroxide, 12 g of aluminum hydroxide/6 g of magnesium hydroxide, 10.5 g of bismuth subsalicylate, 26.25 g of bismuth subsalicylate, and 5% methylcellulose control) with only 1 experiment performed each day. Gastric pH was measured via a glass electrode inserted through the gastric cannula for 1 hour before treatment and continued for 2 hours after treatment. Food or water was not given to the horses during the experiment. Measurements of gastric pH obtained during posttreatment hours were compared with pretreatment gastric pH values. RESULTS: Only a dose of 30 g of aluminum hydroxide/ 15 g of magnesium hydroxide resulted in a significant increase in gastric pH over baseline or control values. Mean pH was 5.2 +/- 0.62 and 4.59 +/- 0.48 for posttreatment hours 1 and 2, respectively. CLINICAL IMPLICATIONS: Oral administration of 30 g of aluminum hydroxide/15 g of magnesium hydroxide to adult horses should result in a mean hourly gastric pH > or = 4.0 for at least 2 hours.     

Effect of antacid on bioavailability of a sustained-release theophylline preparation

The effect of coadministration of an antacid on bioavailability of a sustained-release theophylline tablet preparation (Theo-Dur) was studied by crossover comparison in five young, healthy, nonsmoking volunteers. Water 90 ml, or "high potency" aluminum-magnesium hydroxide antacid (Mylanta II) 10 ml and water 80 ml were administered concurrently with sustained-release theophylline 600 mg. Eleven blood samples were collected over the next 24 hours. Serum was analyzed with high pressure liquid chromatography technique to determine theophylline concentration. Peak serum concentration (Cmax) and time to peak concentration (tmax) were determined, and area under the 24-hour serum concentration-time curve (AUC) was calculated by the trapezoidal rule for each subject at each study interval. The Student's paired t-test was used to compare Cmax, tmax, and AUC for both treatments. A uniform difference was found between groups in Cmax. Cmax was higher in subjects when treated with the antacid (10.45 +/- 3.03 vs. 8.30 +/- 2.90 micrograms/ml, p less than 0.05) than when given theophylline alone. The mean tmax for the two treatments did not differ (10.4 +/- 1.67 h-combination vs. 10.8 +/- 1.1 h-theophylline, p greater than 0.05). Likewise, mean AUC was unchanged by the coadministration of antacid (140.65 +/- 41.6 micrograms/ml.h--combination vs. 155.13 +/- 46.6 micrograms/h--theophylline, p greater than 0.05). The use of a high-potency antacid product did not decrease the extent of theophylline absorption from this sustained-release product, but did increase Cmax and, presumably, rate of absorption. High-potency aluminum-magnesium antacids can probably be used in combination with this sustained-release theophylline tablet without detriment to therapy.     

Decreased bioavailability of digoxin due to antacids and kaolin-pectin

Employing a Latin-square design and single-dose studies of bioavailability in 10 normal human volunteers, we tested the hypothesis that antacids and kaolin-pectin might interfere with the bioavailability of orally administered digoxin. Cumulative six-day urinary digoxin excretion (expressed as the percentage of a 0.75-mg dose recovered) was: control, 40.1+/-3.0 (S.E.); aluminum hydroxide, 30.7+/-2.9; magnesium hydroxide, 27.1+/-2.4; magnesium trisilicate, 29.1+/-1.7; and kaolin-pectin 23.4+/-2.0. The differences in means were highly significant (F = 10.47, P less than 0.005). Further analysis (multiple comparison test) revealed that control differed significantly from each of the other treatments (alpha = 0.05), but there was no such difference between any of the other treatment groups. The decreased cumulative excretion produced by antacids and kaolin-pectin reflected a striking reduction in digoxin absorption associated with these compounds that was not related to alteration of gut transit time or to adsorption of digoxin to these gastrointestinal medications.     

标准加入-电感耦合等离子体原子发射光谱法测定锑铍芯块中铁镁锰铅铝

在锑铍芯块中,锑的质量分数为80%左右,铍的质量分数为20%左右。铍的存在会干扰电感耦合等离子体原子发射光谱法(ICP-AES)测定铁、镁、锰、铅、铝,另外锑的水解也会影响测定。试验使用盐酸、硝酸和酒石酸处理样品,选择Fe 240.488nm、Mg 285.213nm、Mn 259.373nm、Pb 182.205nm、Al 308.215nm作为分析谱线,采用标准加入法(MSA)绘制校准曲线可消除铍、锑基体效应的影响,酒石酸也可完全抑制锑的水解,使用ICP-AES测定铁、镁、锰、铅、铝,从而建立了锑铍芯块中铁、镁、锰、铅、铝等杂质元素的分析方法。各元素在10~400μg/g范围内,校准曲线的线性相关系数均大于0.9998;方法中各元素的检出限为0.48~3.6μg/g。实验方法用于测定2个铍锑芯块样品中铁、铅、镁、锰、铝,结果的相对标准偏差(RSD,n=11)为1.1%~4.9%。按照实验方法和其他方法(铁、铅、镁、锰采用原子吸收光谱法,铝使用分光光度法)测定2个锑铍芯块样品中铁、铅、镁、锰、铝,测定结果相一致。     

标准加入-电感耦合等离子体原子发射光谱法测定锑铍芯块中铁镁锰铅铝

在锑铍芯块中,锑的质量分数为80%左右,铍的质量分数为20%左右。铍的存在会干扰电感耦合等离子体原子发射光谱法(ICP-AES)测定铁、镁、锰、铅、铝,另外锑的水解也会影响测定。试验使用盐酸、硝酸和酒石酸处理样品,选择Fe 240.488nm、Mg 285.213nm、Mn 259.373nm、Pb 182.205nm、Al 308.215nm作为分析谱线,采用标准加入法(MSA)绘制校准曲线可消除铍、锑基体效应的影响,酒石酸也可完全抑制锑的水解,使用ICP-AES测定铁、镁、锰、铅、铝,从而建立了锑铍芯块中铁、镁、锰、铅、铝等杂质元素的分析方法。各元素在10~400μg/g范围内,校准曲线的线性相关系数均大于0.9998;方法中各元素的检出限为0.48~3.6μg/g。实验方法用于测定2个铍锑芯块样品中铁、铅、镁、锰、铝,结果的相对标准偏差(RSD,n=11)为1.1%~4.9%。按照实验方法和其他方法(铁、铅、镁、锰采用原子吸收光谱法,铝使用分光光度法)测定2个锑铍芯块样品中铁、铅、镁、锰、铝,测定结果相一致。     

Cerivastatin

Cerivastatin is a synthetic HMG-CoA reductase inhibitor with high liver selectivity, which lowers plasma cholesterol levels by inhibiting endogenous cholesterol synthesis. In vitro, the affinity of cerivastatin for HMG-CoA reductase was higher than that of lovastatin, simvastatin and pravastatin. This higher enzyme affinity was reflected in vivo, with a lower ED50 (dose causing 50% inhibition) for cerivastatin in rats and beagle dogs compared with lovastatin. Cerivastatin 0.2 mg/day significantly reduced low density lipoprotein (LDL)-cholesterol, total cholesterol and triglyceride levels, and increased high density lipoprotein (HDL)-cholesterol levels, in patients with type IIa hypercholesterolaemia. Available data indicate that cerivastatin has a tolerability profile similar to that of other HMG-CoA reductase inhibitors. No drug interactions were observed when cerivastatin was coadministered with digoxin, warfarin, cimetidine or the antacid magnesium/aluminium hydroxide.     

Bioavailability of morphine after administration of a new bioadhesive buccal tablet

A new bioadhesive buccal morphine tablet was developed for controlled release delivery of drug and improved bioavailability compared with oral controlled release tablet. In order to characterize the pharmacokinetic properties of this bioadhesive buccal formulation, a bioavailability study was performed in 12 healthy volunteers who received: a 30 mg oral controlled release tablet (A); a 20 mg aqueous solution retained in the mouth for 10 min (B); and the 60 mg bioadhesive buccal tablet placed between the lower gum and lip for 6 h (C). The mean amount of morphine absorbed from the solution was very low, only 2 mg of the 20 mg dose. After administration of forms A and C, plasma levels exhibit typical sustained release concentration-time curves. The mean amount of drug recovered from the residual bioadhesive buccal tablet after 6 h indicated that approximately 50% of the dose was released from the bioadhesive buccal tablet. The relative bioavailability of the buccal tablet (corrected for residual unabsorbed dose) compared with the controlled-release tablet was 98% based on the morphine AUC values. Good correlations between the AUC and the Cmax of the bioadhesive tablet for the drug and metabolite plotted versus the amount of morphine absorbed were found.     

EDTA滴定法测定稀土矿石中氧化钙

根据稀土矿石的特性,以氢氧化钠、过氧化钠、碳酸钠熔融分解试样,经过强碱分离铝、硅、氟、磷等杂质元素,氨水分离铁等元素后,用EDTA滴定法测定稀土矿石中氧化钙含量。试验发现经过强碱分离后硅、氟、磷等元素不影响钙的测定结果。讨论了少量铝、钡、锰元素的干扰情况及其干扰消除方法：用三乙醇胺和硫酸钾掩蔽剩余少量Al、Ba等干扰元素,盐酸羟铵掩蔽锰的干扰,加入硫酸镁来改善滴定终点的颜色变化;并实验得出空白值对不同称样量的贡献值也不一样,因为必须做空白实验。在pH>13的氢氧化钾介质中,以钙指示剂为指示剂,EDTA标准溶液滴定稀土矿石中氧化钙,测定值与ICP AES法值相一致,RSD在08%～43%之间。     

EDTA络合滴定法测定稀土镁中间合金中镁

研究了分别采用草酸和氢氧化铵沉淀分离稀土镁中间合金中的稀土,EDTA络合滴定法快速测定电解稀土镁中间合金中镁的两种方法。分析对比了两种方法的适用范围,结果表明,草酸分离稀土方法简便快速,但草酸用量需控制在理论用量的1.2～1.7倍,且合金中铁含量要求小于0.5%;氢氧化铵分离稀土方法分析流程比前者长,但可将主要干扰杂质铁分离完全,终点敏锐。两种方法均已应用于实际产品检测中,测定结果的相对标准偏差为0.69%～1.23%,回收率在97.2%～102.5%之间。     

碱熔-共沉淀富集分离-电感耦合等离子体原子发射光谱法测定钒钛磁铁矿中痕量钪

用过氧化钠-氢氧化钠混合熔剂在750℃的马弗炉中将钒钛磁铁矿试样熔融,再用沸热的三乙醇胺(1+9)浸取熔块,使铁、钛、铝与三乙醇胺络合进入溶液,钒也以含氧酸盐形式进入溶液,向溶液中加入3 mL 10 g/L氯化镁溶液生成氢氧化镁沉淀,溶液中痕量钪则与氢氧化镁共沉淀从而与基体溶液中其他元素分离.过滤沉淀后,采用沸热的盐酸...     

电感耦合等离子体原子发射光谱法测定二硼化钛增强铸铝复合材料中钛硼硅镁锌铁

采用氢氧化钠溶解样品,硝酸酸化,电感耦合等离子体原子发射光谱法(ICP-AES)测定二硼化钛增强铸铝复合材料中钛、硼、硅、镁、锌、铁。分别采用逐级稀释法、标准溶液系列使用基体匹配和无基体匹配这两种方法,考查铝的基体效应。结果表明,样品质量浓度在50～500 μg/mL范围内,铝基体对测定基本无影响。仪器选定的实验条件下,以无基体匹配的标准溶液系列绘制校准曲线,待测元素的线性方程相关系数均大于0.999 6。方法中各元素的检出限在0.000 9%～0.010%之间。将方法应用于TiB₂/AlSi复合材料实际样品中钛、硼、硅、镁、锌、铁的测定,结果的相对标准偏差(RSD,n=11)均小于3%,回收率在94%～113%之间;按照实验方法测定两个铸铝标准样品中硅、镁、锌和铁,测定值与认定值一致。     

电感耦合等离子体原子发射光谱法测定萤石中硅铝铁钾镁钛

样品采用氢氧化钠在锆坩埚中熔融后、再使用硼酸溶液浸取和硝酸酸化,使用电感耦合等离子体原子发射光谱法(ICP-AES)测定硅、铝、铁、钾、镁、钛,从而建立了萤石中硅、铝、铁、钾、镁、钛的测定方法。试验探讨了基体效应的影响,认为溶液中大量存在的钠(4.37~4.83mg/mL)对钾的信号强度稍有影响,但其影响程度小于2.4%,而对其他元素的影响可以忽略;钙(120~200μg/mL)、硼(56.8~85.2μg/mL)和锆(小于4.0μg/mL)对各元素的测定没有显著的影响。试验还考察了酸度的影响,结果表明溶液中一定酸度范围的硝酸对各元素的测定基本没有影响。在选定的工作条件下,各元素的校准曲线呈线性,线性相关系数r为0.999 9~1.000 0,方法检出限为3~105μg/g。方法的测定范围能覆盖所有萤石牌号中硅、铝、铁、钾、镁、钛等元素的测定。按照实验方法测定萤石标准样品YSB 14791-02、GBW07252、GSB 08-1348-2001、Fluorspar 2712中硅、铝、铁、钾、镁、钛,结果的相对标准偏差(RSD,n=5)为0.10%~9.5%,并与认定值相吻合。     

用铝灰制备氢氧化铝的试验研究

作为铝业废渣，铝灰中含有20％～50％的铝。利用铝灰生产氢氧化铝并进而生产高纯聚合氯化铝，能够有效利用资源，消除环境污染。通过试验，提出了用铝灰制备氢氧化铝的工艺流程，并以铝灰中铝的溶出率和氢氧化铝中氧化铝质量分数2个指标，对碱溶法制备氢氧化铝工艺中的影响因素进行了讨论。结果表明，延长反应时间，加大碱的投入量，可以提高铝的溶出率以及成品氢氧化铝中氧化铝的质量分数。     

Fractionation of normal human bone marrow on albumin gradients

An investigation involving seven successive was undertaken on several groups of 10 to 14 volunteers, in order to evaluate any drug interaction between the three active components of Optalidon, namely amidopyrine (A), butalbital (B), and caffeine (C). Each component was investigated after oral administration, alone and in combination either with one of the others (i.e. A+B, B+C, C+A) or with both of the others in Optalidon (A+B+C). The plasma concentration and urinary excretion were recorded for each component as a function of time. For amidopyrine, two metabolites, amino-4-antipyrine and acetamino-4-antipyrine, were also measured in the urine. Based on a pharmacokinetic model, the following conclusions can be drawn: a) There is no change in bioavailability due to the combination of the three components in Optalidon in respect to their single administration. Within each study, there is no significant difference between the elimination rate constants, areas under the plasma concentration/time curve and percentage excreted in urine for the three components administered alone or in any combination with the other components of Optalidon. b) Concerning the absorption half-life, there is no change for amidopyrine. Only caffeine and butalbital show a statistically significant interaction in respect to this parameter and, as a consequence, differences in the time and value of the maximal plasma concentration in Optalidon. However, these differences are scarcely of anyl clinical relevance.     

熔融制样-波长色散X射线荧光光谱法测定石灰石中主次成分

石灰石属碳酸盐矿物,灼烧减量大。已有系列化学分析方法用于石灰石的分析,但这些化学分析方法操作步骤繁杂,化学试剂用量大,分析周期长。实验建立了波长色散X射线荧光光谱法测定石灰石中CaO、MgO、SiO₂、Fe₂O₃、Al₂O₃含量的方法。以测量灼烧减量后的灼烧基试样作为试料,Li₂B₄O₇为熔剂,50 g/L NH₄I溶液为脱模剂,稀释比为1∶10,于1 050 ℃熔融成试料片,以石灰石标准物质作为标准试料制作校准曲线。各待测组分校准曲线的相关系数在0.993 1~0.999 7之间;精密度考察发现,各组分测定结果的相对标准偏差(RSD,n=11)在0.13%~2.1%之间;标准物质的测定值与认定值的偏差在0~0.39%之间。实验方法最大限度地降低了灼烧基试料吸收空气中水分和CO₂对测定结果的影响。     

Pharmacokinetic and bioequivalence study of two gemfibrozil preparations

A comparative pharmacokinetic study has been performed in 19 healthy male volunteers in a single-dose, randomized, two way cross-over design with two preparations of gemfibrozil (CAS 25812-30-0) capsules each of them containing 300 mg active ingredient. The test preparation was Innogem 300 mg capsule. The plasma concentration of gemfibrozil was determined by a validated HPLC-UV analytical method. The statistical comparison of individual pharmacokinetic parameters (AUC0-16, AUC0-oc Cmax, tmax) of the two capsule preparations was performed by three-way analysis of variance (ANOVA), Wilcoxon's, Westlake's, Schuirmann's and Hanck-Anderson's method as well as by the calculation of confidence intervals on the ratio of test/reference. The relative bioavailability of the test preparation with respect to the reference preparation in terms of the AUC0-oc was 104.06 +/- 21.61%. No statistically significant difference was found between the pharmacokinetic parameters, calculated from plasma concentration-time curves, indicating that the two preparations were bioequivalent.     

The in-vitro adsorption of some antirheumatics on antacids

The adsorption of sodium salicylate, salicylamide, acetylsalicylic acid, paracetamol, mefenamic acid, flufenamic acid, phenylbutazone, oxyphenbutazone, phenazone, aminophenazone, indometacin and methiazinic acid on some antacids was studied. The antacids used were magnesium trisilicate, magnesium oxide, aluminium hydroxide, bismuth oxycarbonate, calcium carbonate and kaolin. Magnesium oxide, followed by aluminium hydroxide and bismuth oxycarbonate showed a fairly high adsorptive capacity for salicylates, mefenamic acid, flufenamic acid, methiazinic acid, indometacin and to a lesser extent for phenylbutazone and oxyphenbutazone. On the other hand, magnesium trisilicate exhibited a tendency to adsorb phenazone, aminophenazone, indometacin and methiazinic acid. Kaolin was found to be a good adsorbent for anthranilic acid derivatives, indometacin and methiazinic acid. Calcium carbonate showed a weak adsorptive capacity for all drugs tested. The adsorption of phenylbutazone and salicylates on magnesium oxide, aluminium hydroxide and/or bismuth oxycarbonate obeyed the Freundlich adsorption isotherm. Elution study showed that salicylates and anthranilic acid derivatives were tenaciously held by magnesium oxide while magnesium trisilicate showed an intermediate retention power for phenazone and aminophenazone. Sodium hydrogen carbonate solution gave, in general, a higher eluting power than hydrochloric acid solution. A marked reduction in the apparent partition coefficients of all drugs tested was observed in the presence of magnesium trisilicate or aluminium hydroxide. Careful in vitro and in vivo testing of drug availability is advisable prior to the concomitant administration of antirheumatics with antacids or other adsorbents.