Pharmacokinetics of Fluconazole in Normal Volunteers

The pharmacokinetic profile of fluconazole, after 100 mg i.v. infusion or oral administration of a single 50 mg or 150 mg dose, was investigated in 18 healthy volunteers. At a dose of 100 mg i.v., the half-life (t( 1/2 β)) was 29.73 ± 8.05h. The mean residence time in the plasma was 27.56 ± 5.98 h. The post-distributive volume V(β) = 52.16 ± 9.83 l, approximating that of total bodywater. Renal excretion accounted for 61.64 ± 8.80% of the drug elimination after 48 h, with renal clearance Cl(r) = 12.91 ± 2.83 ml/min. Plasma clearance (Cl(r)) was 21.03 ± 5.07 ml/min. At oral doses of 50 and 150 mg the distribution and elimination of fluconazole resembled that following i.v. infusion. The peak levels in plasma at 2.5 h were 0.93 ± 0.13 and 2.69 ± 0.43 μg/ml, respectively. The large distribution volume, the long half-life and mean residence times, combined with a rapid absorption after oral administration, suggest that fluconazole will be effective at a wide range of body sites.