Hägermark O, Berlin A, Wallin I, Boréus L O
Acta Derm Venereol. 1976;56(4):289-96.
Therapeutic failure of griseofulvin therapy are fairly common, espcially when toe nail infections are treated. The reasons for the failures remain largely unknown. The aim of the present investigation was to study whether pharmacokinetic factors may be responsible. At first, single-dose and steady-state pharmacokinetics of griseofulvin were analysed in volunteers by means of a gas-chromatographic technique. It was found that there was no difference in plasma levels of the three brands of griseofulvin commercially available in Sweden, whereas there was a singificant difference of absorption between individuals. The plasma half-life varied considerably from day to day in the same individual. In the second part of the investigation griseofulvin plasma concentrations were determined in 27 patients treated with griseofulvin for onychomycosis and related to the therapeutic result. All patients but one were initially improved but the therapeutic effect faded in 15 patients after 5-20 months of treatment ("partially healed" patients). In 11 patients the nail infections were clinically healed after 6-24 months. However, no statistically significant difference of the plasma griseofilvin levels could be demonstrated between the healed and partially healed groups. Some possible reasons for the therapeutic failure are discussed.
灰黄霉素治疗失败相当常见，尤其是在治疗趾甲感染时。失败的原因在很大程度上仍不清楚。本研究的目的是探讨药代动力学因素是否可能是其原因。首先，采用气相色谱技术对志愿者进行了灰黄霉素的单剂量和稳态药代动力学分析。结果发现，瑞典市场上销售的三种品牌的灰黄霉素血浆水平没有差异，而个体之间的吸收存在显著差异。同一个体的血浆半衰期每天变化很大。在研究的第二部分，对27例接受灰黄霉素治疗甲癣的患者测定了灰黄霉素血浆浓度，并将其与治疗结果相关联。除1例患者外，所有患者最初均有改善，但15例患者在治疗5 - 20个月后治疗效果消失（“部分愈合”患者）。11例患者在6 - 24个月后指甲感染临床愈合。然而，愈合组和部分愈合组之间的血浆灰黄霉素水平没有统计学上的显著差异。文中讨论了治疗失败的一些可能原因。
