Lazar J D, Wilner K D
Department of Clinical Research, Pfizer Central Research, Groton, Connecticut 06340.
Rev Infect Dis. 1990 Mar-Apr;12 Suppl 3:S327-33. doi: 10.1093/clinids/12.supplement_3.s327.
Fluconazole, a water-soluble bis-triazole antifungal agent that effectively penetrates the cerebrospinal fluid, is a highly selective inhibitor of the fungal cytochrome P450 system. In single-dose studies, coadministration of cimetidine and fluconazole (100 mg) resulted in an insignificant decrease in the absorption of fluconazole. The coadministration of rifampin and fluconazole (200 mg) decreased both the half-life and the area under the plasma concentration-time curve (AUC) of fluconazole. In multiple-dose studies, fluconazole (50 mg) did not significantly alter the pharmacokinetics of the two steroid components of an oral contraceptive. Coadministration of tolbutamide with fluconazole (100 mg) increased both the maximal plasma concentration and the AUC of tolbutamide without changing levels of blood glucose. The coadministration of cyclosporin A with a low dose of fluconazole (100 mg) was not associated with significant changes in the minimal and the maximal plasma concentrations of cyclosporin A. While higher doses of fluconazole (200 mg) did not affect endogenous steroids, coadministration resulted in changes in the pharmacodynamics of warfarin and the pharmacokinetics of phenytoin and cyclosporin A.
氟康唑是一种水溶性双三唑类抗真菌药物，能有效穿透脑脊液，是真菌细胞色素P450系统的高度选择性抑制剂。在单剂量研究中，西咪替丁与氟康唑（100毫克）合用导致氟康唑吸收的减少不显著。利福平与氟康唑（200毫克）合用降低了氟康唑的半衰期和血浆浓度-时间曲线下面积（AUC）。在多剂量研究中，氟康唑（50毫克）未显著改变口服避孕药两种甾体成分的药代动力学。甲苯磺丁脲与氟康唑（100毫克）合用增加了甲苯磺丁脲的最大血浆浓度和AUC，但未改变血糖水平。环孢素A与低剂量氟康唑（100毫克）合用与环孢素A的最小和最大血浆浓度的显著变化无关。虽然较高剂量的氟康唑（200毫克）不影响内源性甾体，但合用导致华法林药效学以及苯妥英和环孢素A药代动力学的变化。
