酮康唑的临床药物动力学。
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Daneshmend TK,沃诺克DW
酮康唑的临床药物动力学。
Pharmacokinet。1988年1月,14 (1):13-34。doi: 10.2165 / 00003088-198814010-00002。
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3280211 (在PubMed]
- 文摘
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酮康唑,合成咪唑抗真菌,对浅表真菌感染有效,生殖器念珠菌病和慢性黏膜与皮肤的念珠菌病,并已用于免疫功能低下的患者和晚期前列腺癌。口服后吸收的酮康唑是可变的,大的变化峰值血清浓度。抗酸药减少,食物或稀盐酸增加,吸收。肾功能衰竭和骨髓移植与减少吸收。酮康唑不是吸收系统后局部管理和最低限度地吸收从阴道。酮康唑的分布变化根据组织采样,潜在的疾病和治疗的剂量和持续时间。酮康唑不穿过完整的血脑屏障,和十字架在有限程度上真菌脑膜炎。尿酮康唑的浓度通常是低,但阴道和阴道组织浓度与血清。精液浓度对于附睾炎的治疗是不够的。83.7%酮康唑血浆蛋白(以白蛋白为主),和15.3%的红细胞绑定,导致只有1%的免费药物。 Animal studies indicate strong binding to the cytochrome P-450 mono-oxygenase complex. Extensive metabolism to inactive metabolites occurs, the products being mainly excreted in the faeces. Saturable hepatic first-pass metabolism is probable. The half-life of ketoconazole is dose-dependent, increases during long term treatment, suggesting auto-inhibition of metabolism. The kinetics after oral administration fit a 2-compartment model. Drug interactions of theoretical, if not practical, significance include warfarin, chlordiazepoxide, methylprednisolone, cyclosporin and drugs known to induce microsomal enzymes. In each case, some dosage adjustment for ketoconazole, or the interacting drug, may be required.