A Randomized Clinical Trial of Oral versus Intramuscular Delivery of Steroids in Acute Exudative Pharyngitis

Previous study has shown that the use of intramuscular (IM) steroid leads to improved symptoms in patients with group A beta-hemolytic streptococcus (GABHS). OBJECTIVE: To compare oral with IM steroids as an adjunct to antibiotic therapy in the treatment of acute exudative pharyngitis. The null hypothesis was that there would be no difference in effectiveness of oral versus IM steroids. METHODS: The study was a randomized, double-blind outpatient clinical trial. After consent was obtained, each patient was asked to rate his or her pain on a 10-cm numbered visual analog scale (VAS; 0-10). All of the patients received injectable benzathine penicillin or, if allergic to penicillin, a ten-day course of polyenteric-coated erythromycin. Each patient was randomized to receive either injectable steroid plus oral placebo or injectable placebo plus oral steroid. All medications were given in the emergency department. All patients were contacted by telephone at 24 hours (first follow-up) and 48 hours (second follow-up) by one of the study investigators and asked to rate their pain based on another VAS. If their pain was not resolved by 48 hours, they were called again daily for the third to seventh day after the initial visit. The time to total resolution of the sore throat was documented. The main outcome measures were time to complete relief of pain and VAS scores. Pain medication was not controlled; however, use of pain medications and amounts were recorded. RESULTS: A total of 78 patients were initially enrolled in the study. Eight patients were excluded from the statistical analysis because of inability to follow up. A total of 70 were entered, with 35 randomized to IM steroid plus oral placebo and 35 to IM placebo plus oral steroid. There was no difference in pain scores for the oral versus IM group at first follow-up (p = 0.13) and second follow-up (p = 0.82), and in number of hours to relief of pain (p = 0.06). Using repeated-measures analysis of variance, no difference in the effects of the two medications over time was detected (p = 0.83). CONCLUSIONS: The results of this clinical trial suggest that oral steroid and IM steroid provide similar levels of pain relief in acute exudative pharyngitis.     

Recent advances in search of oral heparin therapeutics

Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are first choices of clinicians among available anticoagulants. Currently, these agents are administered either parenterally or subcutaneously, which reduces patient compliance and acceptability. Oral heparin may serve as an alternative to both parenteral heparin as well as presently available oral anticoagulants such as warfarin. This review focuses mainly upon recent perspectives in the development of heparin as an oral anticoagulant. The possibility of its success with special emphasis to nanotechnological approaches has been elaborated. Important strategies such as the use of penetration enhancers, the development of lipid conjugates of heparin, and the incorporation of heparin in polymeric matrix systems have been discussed. Additionally, introductory information on biological activities, physiochemical aspects, and pharmacokinetic and pharmacodynamic parameters of heparin is summarized. A brief comparison of UFH and LMWH is also included for reader's benefit. Informative discussion on clinical trials with the successes and limitations of oral heparin formulations is also presented. Overall, the present review provides complete insight to the research that has been carried out for the development of heparin as oral anticoagulant.     

提高老年患者口服用药的安全护理对策

目的提高老年患者口服用药的护理安全，预防老年患者口服用药不良反应事件的发生，防止继发药源性疾病。方法调查和分析不同年龄段老年患者疾病种类、口服药物种类、数量及服药情况。结果随着年龄增长、疾病增多，老年患者口服用药种类、数量显著增加；老年患者口服用药缺乏监督和查对，遵医行为差；临床用药健康教育开展不足。结论加强多方合作，共同努力是提高老年患者口服用药护理安全的关键。     

An Assessment of Pharmacokinetic Interaction Between Lobeglitazone and Sitagliptin After Multiple Oral Administrations in Healthy Men

PurposePatients with type 2 diabetes mellitus require strict blood glucose control, and combination therapy with a thiazolidinedione and dipeptidyl peptidase-4 inhibitors, such as lobeglitazone and sitagliptin, is one of the recommended treatments. The objective of this study was to investigate a possible pharmacokinetic interaction between lobeglitazone and sitagliptin after multiple oral administrations in healthy Korean men.MethodsTwo randomized, open-label, multiple-dose, 2-way crossover studies were conducted simultaneously in healthy men. In study 1, men were randomly assigned to 1 of 2 sequences, and 1 of the following treatments was administered in each period: 1 tablet of lobeglitazone sulfate (0.5 mg) once daily for 5 days and or 1 tablet each of lobeglitazone sulfate (0.5 mg) and sitagliptin (100 mg) once daily for 5 days. In study 2, men were also randomly assigned to 1 of 2 sequences and the treatments were as follows: 1 tablet of sitagliptin (100 mg) once daily for 5 days or 1 tablet each of sitagliptin (100 mg) and lobeglitazone sulfate (0.5 mg) once daily for 5 days. Serial blood samples were collected up to 48 h after dosing on the fifth day. Plasma drug concentrations were measured by LC-MS/MS. Pharmacokinetic parameters, including C_max,ss and AUC_0–τ , were determined by noncompartmental analysis. The geometric least-square mean (GLSM) ratios and associated 90% CIs of log-transformed C_max,ss and AUC_0–τ for separate or coadministration were calculated to evaluate pharmacokinetic interactions.FindingsNineteen men from study 1 and 17 from study 2 completed the pharmacokinetic sampling and were included in the analyses. The GLSM ratios of C_max,ss and AUC_0–τ were 0.9494 (95% CI, 0.8798–1.0243) and 1.0106 (95% CI, 0.9119–1.1198) for lobeglitazone (from study 1) and 1.1694 (95% CI, 1.0740–1.2732) and 1.0037 (95% CI, 0.9715–1.0369) for sitagliptin (from study 2), respectively.ImplicationsExcept for the slight 17% increase in the sitagliptin C_max,ss value, the pharmacokinetic parameters of lobeglitazone and sitagliptin met the pharmacokinetic equivalent criteria when administered separately or in combination. The increase in C_max of sitagliptin when coadministered with lobeglitazone would not be clinically significant in practice. ClinicalTrials.gov Identifier: NCT02824874 and NCT02827890.     

2007～2008年我院妇科口服中成药应用分析

目的：分析妇科口服中成药的用药情况,为临床合理用药提供依据。方法：对我院2007～2008年妇科口服中成药用的种类、用量、销售金额、用药频度、日均费用等进行分析。结果：妇康丸、益母草胶囊、五加生化胶囊临床应用广泛,而宫血宁胶囊受同类西药品种的影响,其用药量呈大幅下降趋势,一些新进药品如大黄蛰虫片使用量呈快速上升趋势。结论：我院妇科口服中成药使用情况基本合理。     

Alkylated poly( -lysine citramide) as models to investigate the ability of amphiphilic macromolecular drug carriers to physically entrap lipophilic compounds in aqueous media

Poly( -lysine citramide) was synthesized to serve as a polymeric bioresorbable drug carrier. It was previously shown that low molecular weight poly( -lysine citramide) hydrophobized with heptyl and lauryl side chains (PLCA-C7_p with p=43 and 60%; and PLCA-C12_p, with p=68, 75 and 100%) formed aggregates in aqueous media. The size of these aggregates was found to depend on the balance between repulsive electrostatic charges and attractive hydrophobic interactions, on the degree of ionization, and on the ionic strength. In this paper, the formation of these aggregates was further investigated by fluorescence probing, using two polarity sensitive molecules, pyrene and Nile Red, which were physically entrapped within the lipophilic core of the aggregates. In contrast to other micellar structures formed by surfactants and amphiphilic block copolymers, aggregates were observed even at very low polymer concentrations. The capacity of the hydrophobic domains to accommodate lipophilic molecules via physical entrapment was demonstrated with progesterone.     

A fluorescent chromophore TOTO‐3 as a ‘smart probe’ for the assessment of ultrasound‐mediated local drug delivery in vivo

Many potent anti‐cancer drugs have an intracellular mode of action, but are limited in crossing the cell membrane, resulting in a reduced clinical efficacy. Ultrasound (US) is known to facilitate the penetration of drugs into tumors cells. However (molecular) imaging techniques that monitor in vivo the underlying processes of US‐triggered drug delivery are lacking. The objective of this study was to demonstrate the feasibility of using a fluorescent nuclear acid stain (TOTO‐3) as a model drug to monitor in real‐time US‐mediated delivery by in vivo fluorescence imaging. Following co‐injection of TOTO‐3 and microbubbles US was applied to the tumor. The time course of the drug delivery process was monitored by fluorescence imaging. Immunohistological analysis and in vitro experiments were performed to investigate the results in more detail. A significant signal intensity enhancement of the US‐treated tumor was observed that indicates intracellular delivery of the dye. In the control tumor TOTO‐3 signal was strongly associated with macrophages, which was not the case for the sonicated tumor. The capability of macrophages to uptake TOTO‐3 was confirmed in vitro. This study demonstrates that an optical contrast agent with similar characteristics to an anti‐cancer drug may be used for continuous in vivo monitoring of the drug delivery process. Copyright © 2010 John Wiley & Sons, Ltd.