A systematic review of the clinical pharmacokinetics of fluconazole in healthy and diseased populations.

INTRODUCTION Fluconazole is a triazole antifungal agent commonly used to treat both systemic and superficial fungal infections. This comprehensive review aims to collate all published pharmacokinetic (PK) data on fluconazole in healthy and diseased subjects.

Methods

A systematic search of Google Scholar, PubMed, and the Cochrane Library identified 40 clinical PK studies of fluconazole that met inclusion criteria.

Results

In healthy volunteers, oral fluconazole (100 mg) achieved a maximum plasma concentration (Cmax) of 2.184 ± 0.427 µg/mL and peak time (Tmax) of 2.6 ± 1.4 h, while IV administration produced a steady-state area under curve from 0 to t (AUC0-t) of 608 ± 115.4 µg.h/mL. In diseased populations, fluconazole PK varied according to the underlying clinical condition, including renal and hepatic impairment, peritoneal dialysis, and neoplastic disease. Patients with moderate renal impairment following IV administration exhibited a higher Cmax (15.7 ± 2 ug/mL) than those with severe renal impairment (12.5 ± 1.24 ug/mL). Following a 150 mg oral dose, AUC0-t was higher under fasting than fed conditions (123.600 ± 16.760 vs. 113.000 ± 15.339 µg.h/mL).

Conclusions

This systematic review compiles fluconazole PK data to support dose optimization in renal impairment and minimize toxicity and drug-drug interactions.