Pharmacokinetic profile of tamsulosin OCAS

The tamsulosin oral‐controlled absorption system (OCAS®) is a new tablet formulation of the α₁‐adrenoceptor (α₁‐AR) antagonist tamsulosin, which is used for treating lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). The tablet uses the OCAS technology, which was specifically designed to give a more continuous 24‐h release of tamsulosin, resulting in a more consistent and continuous 24‐h plasma concentration, a lower maximum plasma concentration (C_max) and an independence of pharmacokinetics (PKs) on food intake. It was expected that the improved PK profile would translate into a better control of day‐ and night‐time symptoms of BPH and a lower risk of adverse events. Phase I PK studies showed that tamsulosin OCAS indeed has a flattened PK profile with a lower C_max and a more stable and consistent 24‐h concentration of tamsulosin, independent of food intake, compared to conventional tamsulosin. A study combining γ‐scintigraphy and PK analysis of blood samples confirmed that the improved PK profile of tamsulosin OCAS is attributed to the tablet being consistently and continuously released throughout the entire gastrointestinal tract, including the colon.     

Randomised trial of long term effect of acupuncture for shoulder pain

Guerra de Hoyos JA, Andres Martin Mdel C, Bassas y Baena de Leon E, Vigara Lopez M, Molina Lopez T, Verdugo Morilla FA, Gonzalez Moreno MJ. Pain. 2004 Dec;112(3): 289-98.The objective of the study is to compare the efficacy of electro-acupuncture with placebo-acupuncture for the treatment of shoulder pain. This study comprised of a prospective, randomized, placebo controlled trial, with independent evaluator set in a Public primary care clinic in Spain. The participants are patients aged from 25 to 83 years with shoulder pain. Patients were randomly allocated to two treatments over eight weeks, with electro-acupuncture or skin non-penetrating placebo-acupuncture, both able to take diclofenac if needed for intense pain. Primary outcome measure was the difference between groups in pain intensity (visual analogue scale – VAS). Secondary outcomes were differences between groups in pain intensity measured by Lattinen index, in range of motion (goniometer), functional ability (SPADI), quality of life (COOP-WONCA charts), NSAIDS intake, credibility (Borkoveck and Nau scale) and global satisfaction (10 points analogue scale). Assessments were performed before, during and three and six months after treatment. At six month follow-up after treatment the acupuncture group showed a significantly greater improvement in pain intensity compared with the control group [VAS mean difference 2.0 (95 % CI 1.2–2.9)]. The acupuncture group had consistently better results in every secondary outcome measure than the control group. Acupuncture is an effective long-term treatment for patients with shoulder pain (from soft tissues lesions) in a primary care setting. q2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.     

Design of clinical trials for chronic diseases: implications for periodontal disease

In order to make effective use of the statistical theory of design of clinical trials for chronic diseases such as periodontal disease, certain issues must be considered. Any clinical trial requires that the disease definition be well-specified; that patient eligibility be explicit; that the observation times be explicit; that the duration and endpoint of therapy be specified; that the duration of subsequent followup observation be specified; and that the unit of observation (e.g., tooth, set of teeth, patient) be defined. In a chronic disease, the potential biases that can readily be introduced by self-selection of patients who enter the trial and/or who return for subsequent observation become more important, because subjects are required to remain on treatment and/or observation for prolonged periods. Further, the cyclical nature of some chronic diseases may require special attention to baseline definitions of active disease and disease outcome. These issues are illustrated with examples from clinical trials of hypertension, breast cancer screening, and Polycythemia Vera. Implications for periodontal disease are discussed.     

常压及控制性降压下脊髓急性牵拉损伤比较研究

目的 评价控制性降压是否增加脊髓对牵拉损伤的易感性。材料与方法健康成年杂种犬6只，随机分为常压和控制性降压脊髓牵拉损伤组。观察常压及控制性降压水平下相同程度牵拉损伤后脊髓血流(SCBF)、体感诱发电位(SEP)、神经源性运动诱发电位(NMEP)改变的差异。结果 外周血有创动脉压(MABP)平均下降幅度为40．5％。经SSPS统计软件独立样本t检验，不同牵拉水平下，常压组及低压组的SCBF(％)、SEP波幅(Asep)(％)及NMEP波幅(％)无显著差异。结论 尼卡地平控制性降压不增加脊髓对牵拉损伤的易感性。     

左炔诺孕酮宫内节育器的制备及药物释放研究

采用改性乙烯-醋酸乙烯共聚物(mEVA)作为控释材料制备释放左炔诺孕酮(LNG)4μg/d,预期使用寿命为5年的钥匙形宫内节育器(IUD)。本IUD在体外和在人及动物子宫内均为零级释药。释药速度与释药管管壁厚度或管外内径比的对数成反比,提示本释药体系的释药模武符合膜控制释药的特性。动物血药浓度测定结果表明,家兔子宫内植入IUD 2d后,血中LNG浓度趋于稳定。     

复方18甲基炔诺酮透皮控释传递系统的LNG人体药物动力学与药效学评价

复方18甲基炔诺酮/雌二醇透皮控释传递系统(LNG/E_2 TCDS)能同时恒速释放低剂量的LNG和E_2,在1周内维持一个平稳而有效的LNG血药浓度。药动学与药效学研究证明,该系统释放的LNG能达到血清LNG目标水平,产生有效的排卵抑制(6/6)。LNG/E_2 TCDS可望发展成为一种安全、有效、非侵入性的新型生育调节避孕制剂。     

Conversion of Ouabain-Induced Ventricular Tachycardia in Dogs with Epicardial Lidocaine: Pharmacodynamics and Functional Effects

Epicardial antiarrhythmic drug administration was studied as a therapeutic approach for experimental ventricular tachycardia (VT) in an open-chest dog model. Lidocaine-polyurethane matrices (28%, w/w) were formulated as a model system. Matrices were placed on the left ventricular epicardium in each of 23 anesthetized open-chest dogs with ouabain-induced VT, to evaluate effectiveness in restoring sinus rhythm. Conversion occurred in all animals treated with matrices containing 300 mg or more of lidocaine after 1.5 to 7.0 min. The matrix lidocaine content correlated linearly with the time required for conversion to sinus rhythm (r = 0.75, P = 0.0002); irrespective of matrix size the myocardial/plasma lidocaine ratio was 20.1 ± 4.2 (mean ± SD) at the time of conversion. In a separate series of five dogs without ventricular tachycardia, systolic wall thickening measured with sonomicrometers after 5 min of controlled-release lidocaine administration (500- to 1000-mg matrix lidocaine content, 7.48 ± 3.49-mg/kg dose) was only minimally diminished (–14.1%) and this effect was observed only at the site of matrix placement on the anterior-apical epicardium. In contrast, intracoronary injection of 0.3 or 1.0 mg/kg of lidocaine-HCl resulted in complete elimination of wall thickening or replacement by systolic thinning. Thus epicardial administration of lidocaine from polyurethane matrices was an effective means of treating ouabain-induced ventricular tachycardia. Regional myocardial function in the vicinity of the matrices was modified to a very limited degree, supporting the view that the matrices can be used safely, without serious risk to ventricular contractile performance.     

A phase I/II study of continuous infusion suramin in patients with hormone-refractory prostate cancer : toxicity and response

 Introduction: Suramin is a synthetic polysulfonated naphthylurea which has been used for the treatment of African trypanosomiasis and onchocerciasis, but since the mid-1980s has received attention as a possible antiretroviral and antineoplastic agent. Objective: This clinical trial of suramin was undertaken as a phase I/II study in patients with hormone-refractory prostate cancer, with the hypothesis that the intensity of therapy with suramin could be increased significantly if measures were undertaken to maintain the plasma concentrations of the drug under 300 μg/ml. Methods: We report the clinical results of this trial, wherein patients were treated at three different targeted plasma suramin concentrations (275, 215 and 175 μg/ml) for varying periods of time (2, 4 or 8 weeks), with delivery of the drug by continuous intravenous infusion. Results: The major toxicity observed in this trial was neurologic, consisting of a motor and sensory peripheral neuropathy that resulted in both paresis and paralysis of the limbs. Nearly all of this severe (CTEP grade III, IV) neurologic toxicity was observed in the patients treated at a plasma suramin concentration of 275 μg/ml for 4 or more weeks. A single patient treated at 215 μg/ml for 8 weeks developed moderate (CTEP grade III) proximal lower extremity weakness, and no patient treated at 175 μg/ml developed this toxicity. The second most common toxicity observed was infection of the central venous catheter. The overall response rate for all of the evaluable patients was 17% (13 of 75 patients). In addition, prostate-specific antigen (PSA)-defined responses were observed in six patients receiving therapy at 175 μg/ml, but these responses were confounded by cessation of therapy with flutamide during suramin treatment. Conclusions: In summary, although plasma suramin concentrations were maintained below 300 μg/ml, neurologic toxicity nonetheless occurred with high frequency in patients treated at 275 μg/ml for 4 or more weeks. Therapy at 215 and 175 μg/ml was in general well tolerated, but central venous catheter-related infection, as well as the inconvenience and expense of continuous infusional therapy, make this method of drug delivery impractical. Only moderate antitumor activity was observed during this trial, but it is possible that both continuation of flutamide and flutamide withdrawal during suramin therapy confounded the assessment of suramin’s activity in hormone-refractory prostate cancer. Received: 9 June 1995/Accepted: 18 March 1996