Patzschke K, Ritter W, Siefert H M, Weber H, Wegner L A
Arzneimittelforschung. 1983;33(5):745-50.
[14C]Bifonazole (1-[(4-Biphenylyl)-phenylmethyl]-1H-imidazole, Bay h 4502, Mycospor) was administered systemically (i.v.) and topically (dermally) in different formulations to a total of 17 volunteers. In the serum, the concentrations of total radioactivity and of the unchanged drug were determined by liquid scintillation counting techniques and by thin-layer densitometry, respectively. Urine and feces were collected and radioassayed. The extent of percutaneous absorption was calculated. In addition, distribution of the unchanged drug in the layers of the skin was studied radiometrically in three patients. After intravenous administration, bifonazole was eliminated from the serum largely in metabolized form. The half-lives of elimination of the radioactivity from the serum were approximately 7 and 42 h. Within 5 days 45% of the dose was excreted with the urine, and 39% with the feces. After topical application to healthy skin areas, under occlusive conditions, less than 1% of bifonazole was absorbed percutaneously from a 1% solution or cream, and the amount absorbed was excreted with the urine and the feces in approximately the same proportions as after i.v. administration. Following administration of the drug to inflamed skin, the proportion absorbed was 3 to 4% of the dose administered and thus higher than after application to normal skin. Studies on depth localization showed that the drug has a high capacity for skin penetration. Even in the lower layers of the epidermis, bifonazole was present in amounts several times as high as the minimum inhibitory concentrations for dermatophytes measured in vitro.
[14C]联苯苄唑（1-[(4-联苯基)-苯基甲基]-1H-咪唑，Bay h 4502，霉克）以不同剂型通过静脉全身给药和经皮局部给药，共纳入17名志愿者。血清中总放射性浓度和未代谢药物浓度分别通过液体闪烁计数技术和薄层光密度法测定。收集尿液和粪便并进行放射性测定。计算经皮吸收程度。此外，对3例患者进行放射性测量研究未代谢药物在皮肤各层的分布。静脉给药后，联苯苄唑主要以代谢形式从血清中消除。血清中放射性消除的半衰期分别约为7小时和42小时。5天内，45%的剂量经尿液排出，39%经粪便排出。在封闭条件下，将药物局部应用于健康皮肤区域后，1%溶液或乳膏中联苯苄唑的经皮吸收量不到1%，吸收量经尿液和粪便排出的比例与静脉给药后大致相同。将药物应用于炎症皮肤后，吸收比例为给药剂量的3%至4%，因此高于应用于正常皮肤后的吸收比例。深度定位研究表明，该药物具有很强的皮肤穿透能力。即使在表皮下层，联苯苄唑的含量也比体外测定的皮肤癣菌最低抑菌浓度高出数倍。
