Pharmacokinetics and haemodynamic effects of ISDN following different dosage forms and routes of administration

The pharmacokinetics and haemodynamic effects of isosorbide dinitrate (ISDN) have been investigated following administration of single doses as a sublingual (SL) spray (2.5 mg), sublingual tablet (5 mg) and peroral tablet (10 mg) in a randomised, placebo-controlled double-blind cross-over trial in 16 healthy volunteers.After the sublingual spray C_max was higher (39.0 ng·ml^-1) and t_max was shorter (3.9 min) than after the sublingual (22.8 ng·ml^-1 and 13.8 min) and peroral (16.9 ng·ml^-1 and 25.6 min) tablets. The AUC of ISDN did not differ following any of the three formulations (1031; 879; 997 ng·ml^-1·min, for the spray, SL tablet and PO-tablet, respectively). Mononitrate metabolites of ISDN (IS-2-MN and IS-5-MN) and total nitrates in plasma increased in proportion to the administered dose. This indicates that the fraction of the dose absorbed was the same for all the formulations but that the extent of first-pass metabolism increased in the order sublingual spray < sublingual tablet < peroral tablet. Thus, compared to the spray, the relative bioavailability of ISDN was 48% and 28% from the sublingual and peroral tablets, respectively.The haemodynamic effects were quantified using the a/b ratio of the finger pulse wave and the systolic blood pressure and heart rate under orthostatic conditions. For the a/b ratio of the finger pulse, the maximal effect was higher (e_max=130%) and the time to e_max (t_emax) shorter (16.6 min) after the spray than the sublingual tablet (84.4% and 25.5 min) or peroral tablet (90.2 and 31.3 min). The onset of effect was within 3, 5 and 7.5 min after the spray, sublingual and peroral tablets, respectively. A larger change in the orthostatically-induced decrease in systolic blood pressure and increase in heart rate was obtained following peroral than sublingual administration despite the similar plasma concentrations of ISDN. This probably reflects the larger amount of pharmacodynamically active mononitrate metabolites formed after oral dosing. The integrated effect following administration of 2.5 mg ISDN as spray was similar to that of a sublingual tablet of 5 mg.     

Influence of rate of administration of raclopride on akathisia and prolactin response

The D₂-dopamine receptor antagonist raclopride was administered to eight healthy male subjects, who had previously experienced akathisia following antipsychotic drugs. The influence of administration rate on onset, severity and duration of akathisia and on prolactin response was studied. Raclopride 3,5 or 9 mg or placebo (P) was administered as single IV infusions during 10 min (R10 min/3 mg), 1 h (R1h/5 mg) or 4 h (R4h/9 mg) according to a randomized double-blind design. Despite a 24-fold difference in administration rate a similar peak raclopride concentration of about 350 nmol/l was obtained after all three infusions. Three of the eight subjects experienced akathisia following R10 min/3 mg and R1h/5 mg, respectively. After R4h/9 mg seven subjects experienced akathisia of longer duration but not more severe than after the short infusions. The incidence and duration of akathisia seem to be mainly related to the plasma raclopride concentrations over time, whereas the rate of administration might be more important for the severity. A maximal prolactin response was induced which was not markedly affected by the rate of administration.     

Aminoglycoside therapy Current use and future prospects

The microbiological, pharmacokinetic, toxicological and clinical aspects of aminoglycosides are reviewed. Aminoglycosides still have an important place in serious infections in neutropenic patients, endocarditis andPseudomonas aeruginosa infections, all in combination with beta-lactams. Monotherapy (with streptomycin) is indicated in less common diseases like tularaemia and bubonic plague. Several experimental studies support a oncedaily dosing regimen for aminoglycosides (comparable or better efficacy with less ototoxicity and nephrotoxicity). Only a very limited number of prospective comparative studies have been performed, and much more data on efficacy, development of resistance and toxicity is needed before once-daily administration can be recommended. The choice of an aminoglycoside should be based primarily on the local sensitivity patterns and cost. Differences in ototoxicity and nephrotoxicity are usually minor. If the acquisition costs of amikacin decline, it is to be expected that amikacin will be the aminoglycoside of choice.     

低抗凝肝素来源低分子肝素口服制剂的研究

以生产肝素的副产品——低抗凝肝素为原料,采用亚硝酸控制解聚法制得了低分子肝素,分子量为5300,抗凝活性为39.2u/mg,测定了理化指标。以对家兔实验性血栓形成的影响为药效学指标,确定低分子肝素口服制剂的处方组成为低分子肝素、油酸、牛胆盐。研究了所制备的低分子肝素胶囊对家兔血液流变学及血栓形成的影响,并试用于部分动脉粥样硬化症志愿者,表明该胶囊可有效地改善家免和动脉粥样硬化症志愿者血液流变性质,抑制血栓形成。     

Bone levels of cephradine and cefuroxime after intravenous administration in patients undergoing total hip replacement

Summary A randomised, comparative study is reported of single intravenous doses of cephradine 2 g or cefuroxime 1.5 g given as prophylactic cover for total hip replacements in 40 patients. The serum and bone levels of cephalosporin achieved were higher in the cephradine treated group in proportion to the higher dose employed. Both agents provided adequate bone levels on average, cephradine 25.34 mcg/g, cefuroxime 17.39 mcg/g, although bone penetration was more variable with cefuroxime.

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Résumé Dans cette étude comparative randomisée, 40 patients ont reçu une dose intraveineuse unique de 2 g de céphradine ou de 1,5 g de céfuroxime en tant que couverture prophylactique d'arthroplastie totale de hanche. Les concentrations sériques et osseuses de céphalosporine ont été plus élevées dans le groupe traité par la céphradine, en rapport avec l'utilisation d'une dose plus importante. Des concentrations osseuses adéquates ont été obtenues en moyenne avec les deux produits (25,34 mcg/g avec la céphradine et 17,39 mcg/g avec le céfuroxime) bien que la pénétration osseuse ait été plus variable avec le céfuroxime.

     

SARS患者护理管理与相关因素探讨

探讨门诊护理管理者在大型综合医院应对突发疫情时的管理方法。建立新科室新体制与实施新制度新流程；建立健全消毒、隔离和防护管理制度；严格执行各项制度及工作流程；建立对各类工作人员的全员全面岗前培训考核制度；护理人员的统一协调；明确人员属地管理原则。经过采取上述一系列协调管理措施，使在门诊隔离病房、发热门诊和SARS专用手术室工作的各类人员无一人发生感染。对防止SARS向院内传播起到了重要的作用。     

SARS一线护士的健康调查及防治对策的探讨

目的 调查从事SARS一线护理工作的护士健康状况，为制定合理的卫生保健措施提供可借鉴的建议。方法 对一线工作人员不同时间点的各项生理指标进行观测，并根据结果采取针对措施。结果 一线工作护士各项生理指标均较正常时出现明显波动，采取相应措施后有明显改善。结论 良好的防治措施对改善一线护士的健康状况大有裨益。     

药用新辅料在制剂中的应用

药用新辅料是药物制剂的基础材料和重要组成部分，在制剂剂型的发展和生产中起着关键作用。它不仅赋予药物一定的剂型，并且与提高药物的疗效、降低毒副作用有很大的关系。因此，研究开发、合理应用新辅料不仅是提高我国药物制剂质量和生产技术水平的重要方向，而且可取得较大的社会及经济效益。