Graybill J R
Veterans Administration Hospital, San Antonio, TX 78284.
J Infect. 1994 May;28 Suppl 1:17-24. doi: 10.1016/s0163-4453(94)95926-9.
Effective broad spectrum antifungal therapy has been available since the introduction of amphotericin B three decades ago. Amphotericin B must be given intravenously, and thus access to the bloodstream is assured. Because of the great toxicity of this agent, initial studies were directed at determining a dose which was tolerable and clinically effective. In part because of few data and in part because of major concerns with toxicity, there is at present no established relationship with amphotericin B serum concentrations and clinical outcome, and there is no clear indication for measurement of serum concentrations of this drug. More recently there has appeared a variety of orally administered antifungal azole derivatives. Oral absorption is affected by a variety of factors, and drug access to the blood stream is not readily predictable for some of these drugs. Serum concentrations have not been consistently assessed in clinical studies. Where they have been measured, there does appear to be a loose correlation of clinical response with the detection of some amount of drug in the bloodstream. However, beyond this 'threshold' concentration, there is no compelling evidence for a correlation of serum concentration and clinical outcome. While serum concentration of azoles may be useful in determining absorption of drug, at present there is no impetus for achieving a given concentration in the blood to improve chances of a good outcome.
自三十年前两性霉素B问世以来，有效的广谱抗真菌治疗方法就已存在。两性霉素B必须静脉给药，因此可确保进入血液循环。由于该药物毒性极大，最初的研究旨在确定可耐受且临床有效的剂量。部分由于数据较少，部分由于对毒性的主要担忧，目前两性霉素B血清浓度与临床疗效之间尚无既定关系，且尚无明确指征测量该药物的血清浓度。最近出现了多种口服抗真菌唑类衍生物。口服吸收受多种因素影响，其中一些药物进入血液循环的情况难以预测。临床研究中尚未对血清浓度进行一致评估。在已测量血清浓度的情况下，临床反应与血液中检测到一定量药物之间似乎确实存在松散的相关性。然而，超过这个“阈值”浓度后，没有令人信服的证据表明血清浓度与临床疗效相关。虽然唑类药物的血清浓度可能有助于确定药物吸收情况，但目前没有动力通过达到血液中的特定浓度来提高取得良好疗效的机会。
