Comparative evaluation of methacycline hydrochloride capsules and tablets according to their dissolubility and rate of solution]

Desintegration and dissolution of capsules and tablets of methacycline hydrochloride were studied. The study on solubility of methacycline hydrochliride capsules filled with methacycline granulate or powder according to the same formula showed that the rate of the antibiotic liberation from the capsules filled with the powder decreased during storage while that from the capsules filled with the granulate did not change. Investigation of the effect of the mass packing value in a drop on the antibiotic liberation from the capsules showed that an increase in the packing coefficient above 1.38 resulted in a marked decrease in the rate of methacycline liberation from the capsules filled with the granulate. No correlation between desintegration and dissolution of methacycline capsules and tablets was found.     

Dicloxacillin: its chemotherapeutic action and experimental kinetic characteristics]

Activity against 50 clinical staphylococcal strains, chemotherapeutic efficiency, absorption and distribution of dicloxacillin in animals were studied in comparison with oxacillin. It was found that dicloxacillin was superior to oxacillin with respect to a number of their properties. The antibiotic was characterized by a higher antistaphylococcal activity, especially with respect to methicillin resistant strains. It was more effective in treatment of staphylococcal pneumonia and septicopiemia of albino mice. The drug was better absorpted when used orally and was detected in the blood in therapeutic concentrations for long periods of time. The antibacterial titer of the blood serum after dicloxacillin administration was 4 times higher than that of oxacillin.     

Differentiation of the degree of bioavailability of peroral drug forms of tetracycline hydrochloride in experiments on laboratory animals]

Difference in the levels of bioavailability of 4 types of tetracycline hydrochloride tablets was shown on rabbits and guinea pigs. The rates of the antibiotic absorption into the blood of the laboratory animals and volunteers were the same. Relation between the rate of disintegration of various types of tablets of tetracycline hydrochloride and the antibiotic blood levels in the rabbits after administration of the same tablets was found.     

Erythromycin pharmacokinetics in children after rectal and oral administration

Pharmacokinetics of erythromycin base was studied clinically in children not older than 14 years treated with new children dosage forms of the antibiotic i. e. 0.1 and 0.25 g enteric coated tablets and 0.06 and 0.125 g suppositories. It was noted that the new dosage forms were characterized by higher availability which was 2.5-3 times higher than that after using the erythromycin base tablets without the coating. Systematic increasing of erythromycin availability after the use of the rectal suppositories was observed with increasing of the children age. Absolute absorption in newborns, sucklings and children over 1 year amounted to 28, 36 and 54 per cent respectively.     

辛伐他汀自微乳化胶囊的体内评价

目的:研究辛伐他汀(SV)自微乳化胶囊在比格犬体内的药代动力学。方法:采用HPLC法测定比格犬血浆药物浓度,与市售片比较,考察SV自微乳化胶囊的体内药代动力学。结果:药代动力学测定结果表明:与市售片比较,自微乳化胶囊血药浓度达峰时间提前、最高血药浓度增大,Tmax=1.41h,Cmax=46.22ng.mL-1,而市售片的Tmax=2.65h,Cmax=12.43ng.mL-1;AUC0-∞为市售片剂的227.5%。结论:自微乳化胶囊可以显著提高SV的体内吸收。     

Characteristics of determining the microbial contamination of penicillin series antibiotic powders and tablets]

Optimal conditions for determination of microbial contamination of drugs were studied on artificially contaminated powders and tablets of phenoxymethylpenicillin, ampicillin, oxacillin and dicloxacillin. The method of membrane filtration was the best for determination of the microbial contamination of the powders. However, it was not possible to wash out completely the antibiotic from the membrane filter. To prevent this it was necessary to add penicillinase into the nutrient medium onto which the filter was put for providing the microbial growth. For determination of microbial contamination of tablets direct plating of 3 per cent suspension of the tablet mass onto the surface of the nutrient medium with penicillinase was the best.     

Bioavailability of tetracycline hydrochloride capsules (an in vivo study)]

Blood absorption of tetracycline hydrochloride of various dispersity levels from capsules containing tetracycline alone or in combination with additives, such as magnesium carbonate and calcium salts was studied on humans. It was found that higher dispersity levels of tetracycline hydrochloride powder in capsules was not accompanied by increased blood absorption of the antibiotic. Addition of magnesium carbonate and calcium salts to the antibiotic in the process of capsulation markedly retarded the blood absorption. Clear correlation between the antibiotic dissolution rate in vitro and intensity of its blood absorption in volunteers was shown.     

单方中药马蹄香散剂和几种微生态制剂中氨基酸和微量元素含量的测定和比较

目的 测定马蹄香和微生态制剂中氨基酸和微量元素的含量,深入认识马蹄香和微生态制剂的特点.方法 应用国家标准GB/T 5009.124-2003高效液相法和应用日本岛津公司ICPS-1000Ⅱ型等离子体发射光谱仪测定马蹄香和微生态制剂中氨基酸和微量元素含量.结果 氨基酸含量在乳酸菌素片＞亿活＞马蹄香＞金双歧＞贝飞达＞思连康＞合生原＞妈咪爱.谷氨酸在所有制剂中含量均高,天冬氨酸在多数制剂中含量也高.而胱氨酸在所有制剂中含量均低或未能测出.元素钙、磷、镁和硫含量在马蹄香＞乳酸菌素片＞亿活＞思连康＞金双歧＞妈咪爱＞贝飞达＞合生原.马蹄香中微量元素含量较丰富.结论 马蹄香和不同的微生态制剂所含的氨基酸和微量元素各有特点,这对不同制剂的微量营养素的认识有特殊意义.     

Oesophageal transit of six commonly used tablets and capsules.

The oesophageal transit of six commonly used tablets and capsules containing barium sulphate was evaluated radiologically using fluoroscopy in 121 healthy volunteers. To determine the influence of the subject''s position and the amount of water taken each subject swallowed three preparations while recumbent and standing and with 25 ml or 100 ml of water. Failure of swallowing (defined as oesophageal transit taking more than 90 seconds) occurred in 22% of 726 swallowings, but globus was complained of in only 33% of these. Sixty per cent of the volunteers had difficulty in taking one or more of the preparations. Many preparations adhered to the oesophageal membrane and started to disintegrate in the lower part of oesophagus. It is recommended that subjects should remain standing for at least 90 seconds after taking capsules or tablets and that all preparations should be taken with at least 100 ml of water. Small tablets are swallowed most easily. Liquid forms of medication (suspensions) should be considered for bedridden patients and those who have difficulty in swallowing.     

Pharmacokinetics of penicillins in the blood of dogs administered the combination preparation, ampiox, internally]

The pharmacokinetics of penicillins in the blood of dogs treated with ampiox, a combination of ampicillin and oxacillin at a ratio of 1 : 1 was studied. The drug was administered orally in single or repeated doses of 25, 50 and 100 mg/kg. The maximum levels of ampicillin in the blood serum were observed 1 hour after a single administration of the drug. The therapeutic concentrations of the antibiotic were preserved for 6 hours, its value being depended on the dose used. The maximum concentration of oxacillin was detected 1 hour after the drug administration in various doses and it was preserved in the blood at the therapeutic levels for 3 hours. The dynamics of circulation of ampicillin and oxacillin administered separately did not differ from that established for the use of ampiox. The regularities of the pharmacokinetics of ampiox on its repeated use remained practically unchanged.     

Use of the penicillanic acid formation reaction for the analysis of penicillins. The quantitative determination of oxacillin]

A procedure for quantitative determination of oxacillin by means of spectrophotometry is described. The procedure is based on the capacity of penicillins to transform on heating in acid buffer solutions containing copper ions into respective penicillenic acids having specific absorption characteristics in the UV-spectrum region. The amount of oxacillin was estimated by the optical density of the solutions at a wave length of 335 nm corresponding to the absorption maximum of the penicillenic acid of oxacillin. The optimal conditions for the reaction of the penicillenic acid formation, i.e. pH of the buffer solution and the level of the copper ions in it, time and temperature of heating were determined. The data on the comparison of the specificity and reproducibility of the new method with the currently used ones for determination of oxacillin are presented.     

Doxycycline bioavailability in capsules]

Soviet doxycycline capsules in a dose of 0.1 g were studied in vitro (for disintegration and solubility) and in vivo (pharmacokinetics on 25 patients). It was found that Soviet doxycycline capsules provided comparatively rapid absorption of doxycycline. The antibiotic availability may be characterized by the solubility test. The results of the study on bioavailability of Soviet doxycycline capsules were compared with the results of analogous studies published by American authors for doxycycline capsules manufactured by various firms of the USA.     

Oxacillin-induced inhibition of protein and RNA synthesis in a tolerant Staphylococcus aureus isolate.

A clinical isolate of Staphylococcus aureus was found to be tolerant (MBC much greater than MIC) to a number of beta-lactam antibiotics, including oxacillin. Biophotometric analysis showed that a number of concentrations of oxacillin were capable of stimulating rapid cellular lysis in this organism, but the extent of lysis was antibiotic concentration dependent and limited. Cell cultures treated with an antibiotic concentration yielding the maximum rate and extent of lysis were analyzed for protein and RNA synthesis by pulse-labeling techniques. RNA synthesis was initially stimulated and then severely inhibited. Protein synthesis was not inhibited initially; however, the increase in the rate of synthesis expected as the result of logarithmic growth was not observed. Instead, the antibiotic-treated culture maintained for approximately 50 min the rate of protein synthesis ongoing at the time of antibiotic addition. The rate of protein synthesis declined thereafter. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of protein samples taken 1 and 3 h after antibiotic addition showed that the shutdown of protein synthesis was not coordinate but rather was suggestive of the operation of a stress regulon perhaps similar to those responsible for heat shock, SOS, and oxidation stress.     

The Effects of Peritoneal Dialysis on the Physiological Disposition of Oxacillin,Ampicillin and Tetracycline in Patients with Renal Disease

Seven patients with acute or chronic renal failure who were receiving intermittent peritoneal dialysis and who required parenteral oxacillin, ampicillin or tetracycline were studied to determine the disposition of these antibiotics in severe renal disease and the effects of peritoneal dialysis. While severe renal impairment markedly prolongs persistence in the serum of ampicillin and tetracycline, there is little effect on oxacillin. Whereas required doses of ampicillin and tetracycline are lower in the presence of severe renal disease, oxacillin should be given in doses equivalent to those used for patients with normal renal function. Peritoneal dialysis does not alter these dosage requirements.Four patients receiving ampicillin or tetracycline in the infusing solution during peritoneal dialysis were studied to determine the amount of systemic absorption. Local prophylaxis alone is not achieved with this method of administration, since small amounts of both antibiotics are absorbed systemically from the infusing solution. The serum concentration of tetracycline attained is inadequate for treatment of systemic infections but is probably significant, with repeated use in intermittent dialysis, in causing adverse effects. Tetracycline should be abandoned in the local prophylaxis of peritonitis during peritoneal dialysis.     

Thioridazine affects transcription of genes involved in cell wall biosynthesis in methicillin-resistant Staphylococcus aureus

The antipsychotic drug thioridazine is a candidate drug for an alternative treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in combination with the β-lactam antibiotic oxacillin. The drug has been shown to have the capability to resensitize MRSA to oxacillin. We have previously shown that the expression of some resistance genes is abolished after treatment with thioridazine and oxacillin. To further understand the mechanism underlying the reversal of resistance, we tested the expression of genes involved in antibiotic resistance and cell wall biosynthesis in response to thioridazine in combination with oxacillin. We observed that the oxacillin-induced expression of genes belonging to the VraSR regulon is reduced by the addition of thioridazine. The exclusion of such key factors involved in cell wall biosynthesis will most likely lead to a weakened cell wall and affect the ability of the bacteria to sustain oxacillin treatment. Furthermore, we found that thioridazine itself reduces the expression level of selected virulence genes and that selected toxin genes are not induced by thioridazine. In the present study, we find indications that the mechanism underlying reversal of resistance by thioridazine relies on decreased expression of specific genes involved in cell wall biosynthesis.     

Polymeric surfactant based etodolac chewable tablets: formulation and in vivo evaluation

Etodolac (ET) is a nonsteroidal anti-inflammatory drug with proved potential antitumor and uric acid lowering effects. It shows dissolution rate-dependent bioavailability. This work was carried out to improve the dissolution rate of etodolac using three carriers of known potential to improve solubility and hence dissolution rate of poorly soluble drugs through coevaporation technique. The polymeric surfactant inutec, 2-hydroxypropyl-β-cyclodextrin, and tromethamine were used at three different drug/carrier ratios. The dissolution rate of ET at pH 1.2 and 6.8 is improved in all of the solid dispersion systems compared to that of the pure drug and physical mixtures. DSC of coevaporates at 1:5 drug/carrier ratio providing the fastest dissolution rate suggested loss of ET crystallinity which was further confirmed by X-ray diffraction. Inutec-based coevaporate was chosen for the formulation of ET chewable tablets. Chewable tablets (F3) that met the USP monograph specifications for ET tablets, with 86% dissolved amount within 15 min, was chosen for in vivo absorption study in comparison with pure ET-filled hard gelatin capsules. The results showed significantly higher mean C _max and shorter mean T _max (about 2 h earlier) and about 1.32-fold higher mean AUC_0–24 values for the F3 chewable tablets compared to ET-filled capsules.     

Evaluation of oxacillin and cefoxitin disks for detection of resistance in coagulase negative staphylococci

Coagulase-negative Staphylococcus spp. was considered nonpathogenic until the emergence of multiresistance and the demonstration of their participation as infectious agents. In Brazil, oxacillin resistance may be present in over 80% of isolates, and the Clinical and Laboratory Standards Institute standardized a disk-diffusion method to predict this resistance in Staphylococcus. The aim of this study was to evaluate the variability among commercial disks of oxacillin (1 microg) and cefoxitin (30 microg) widely used in clinical laboratories of microbiology, compared with mecA gene and minimum inhibitory concentration (MIC) of oxacillin. The use of oxacillin and cefoxitin disks simultaneously allowed the detection of important differences, particularly, in less frequent species such as S. cohnii, S. haemolyticus, S. saprophyticus, and S. sciuri. Disks of cefoxitin of the brand 2 displayed good correlation with the mecA gene (98.7%) and oxacillin MIC (97.8%), while major discrepancies were observed using disks of brand 1. One of the critical points in the diffusion disk test is the quality of the disks: the use of better quality disks associated with molecular methods lead to better results to define the best antibiotic therapy.     

Antibiotics in surgical treatment of acute abscesses.

A four-way, double-blind, prospective trial of treatment of abscesses by incision, curettage, and primary closure with and without antibiotic cover (clindamycin injection before operation or capsules after operation, or both) was conducted. There was no appreciable difference in mean healing time between the patients given both the antibiotic injection and the antibiotic capsules and those given the injection and placebo capsules, whereas healing times in those given the placebo injection and antibiotic capsules or placebo only were appreciably longer. Four of the patients who were not given the antibiotic injection developed bacteraemia; one patient who was given the antibiotic injection also developed a bacteraemia, but this was caused by clindamycin-resistant bacteria. These results show that a single injection of an effective antibiotic before operation is sufficient to protect the patient against bacteraemia and permit optimum healing.     

Capsules with Lycopodium spores for absolute diatom and pollen analysis

Lycopodium spore capsules have been produced as a slight modification of the widely used Lycopodium spore tablets introduced by Stockmarr in 1971. The spore content is increased in the capsules to facilitate their use in absolute diatom analysis.     

百令胶囊联合厄贝沙坦片对膜性肾病患者MMP-9, MMP-3和TIMP-1水平的影响

目的:探究百令胶囊联合厄贝沙坦片对膜性肾病患者基质金属蛋白酶-9、3和金属蛋白酶组织抑制物-1影响。方法:收集我院肾内科收治的膜性肾病患者98例,根据随机对照表分为对照组和试验组,每组49例。对照组给予厄贝沙坦片治疗,试验组联合百令胶囊治疗。对比分析两组患者的临床疗效、血清Scr、BUN、UA、Ccr、尿蛋白、MMP-9、MMP-3及TIMP-l水平以及不良反应的发生情况。结果:治疗后,对照组临床总有效率为81.63%,显著低于试验组的95.92%(P0.05)。两组治疗后血清Scr、BUN、UA、MMP-9、MMP-3、TIMP-l水平均显著降低,且试验组显著低于对照组(P0.05),Ccr水平升高,且试验组显著高于对照组(P0.05)。对照组不良反应发生率为10.20%,试验组为6.25%,差异无统计学意义(P0.05)。结论:百令胶囊联合厄贝沙坦片对膜性肾病患者的临床疗效显著,安全性较高,可能与其显著降低MMP-9、MMP-3和TIMP-1水平有关。