Faergemann J, Laufen H
Department of Dermatology, University of Gothenburg, Sahlgren's Hospital, Sweden.
Clin Exp Dermatol. 1993 Mar;18(2):102-6. doi: 10.1111/j.1365-2230.1993.tb00987.x.
The distribution in the skin of orally active antifungals and other drugs claimed to be active in the treatment of skin diseases is of major importance, but to date has been studied only rarely. In the present study the distribution of fluconazole in stratum corneum, epidermis-dermis (without stratum corneum), eccrine sweat and serum was studied in human male volunteers after dosages of 50 mg daily for 12 days and 150 mg once weekly for 2 weeks. In the present study high levels of fluconazole were found especially in the stratum corneum. At a dose of 50 mg once daily the concentration of fluconazole after 12 days was 73.0 micrograms/g and 7 days after cessation of treatment the concentration was still 5.8 micrograms/g. At the 150 mg once a week dose the concentration 7 days after the second dose was still 7.1 micrograms/g in stratum corneum indicating that medication once a week may be effective in the treatment of dermatomycoses. High concentrations, all above the serum concentrations, were also seen in sweat and epidermis/dermis. These results indicate that fluconazole is delivered to the stratum corneum, where it is accumulated, through sweat and by direct diffusion through the dermis-epidermis. These pharmacokinetic results indicate that the drug should be very effective in the treatment of dermatomycoses. An extremely high concentration of the drug in the stratum corneum combined with concentrations from 2.93 to 4.62 micrograms/g in the rest of the epidermis and dermis is important in the treatment of these diseases.
口服活性抗真菌药物以及其他声称对皮肤病治疗有效的药物在皮肤中的分布至关重要，但迄今为止对此研究甚少。在本研究中，对男性志愿者连续12天每日服用50毫克以及连续2周每周服用一次150毫克后，研究了氟康唑在角质层、表皮 - 真皮（不包括角质层）、外分泌汗腺和血清中的分布情况。在本研究中，尤其在角质层中发现了高浓度的氟康唑。每日一次服用50毫克剂量，12天后氟康唑浓度为73.0微克/克，停药7天后浓度仍为5.8微克/克。每周一次服用150毫克剂量，第二次服药7天后角质层中的浓度仍为7.1微克/克，这表明每周用药一次可能对皮肤癣菌病治疗有效。在汗液和表皮/真皮中也观察到高浓度，均高于血清浓度。这些结果表明，氟康唑通过汗液以及经真皮 - 表皮直接扩散进入角质层并在其中蓄积。这些药代动力学结果表明该药物在皮肤癣菌病治疗中应非常有效。角质层中极高的药物浓度，以及表皮和真皮其他部位2.93至4.62微克/克的浓度，对这些疾病的治疗很重要。
