Is there a correlation between serum antifungal drug concentration and clinical outcome?
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.
Graybill
J R
JR
Veterans Administration Hospital, San Antonio, TX 78284.
D000284:Administration, Oral; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D000935:Antifungal Agents / Q000097:blood*; D006801:Humans; D007275:Injections, Intravenous; D017964:Itraconazole / Q000493:pharmacokinetics; D007654:Ketoconazole / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000097:blood / Q000188:drug therapy*; D010879:Piperazines / Q000493:pharmacokinetics; D012307:Risk Factors; D016896:Treatment Outcome
D000935:Antifungal Agents; D010879:Piperazines; D017964:Itraconazole; D000666:Amphotericin B; D007654:Ketoconazole