Comparison of fluconazole pharmacokinetics in serum, aqueous humor, vitreous humor, and cerebrospinal fluid following a single dose and at steady state

The objective of this study was to characterize the pharmacokinetic paramet ers and penetration of fluconazole following a single dose in the serum, aq ueous humor, vitreous humor and cerebrospinal fluid (CSF) of non pigmented rabbits using serial sampling techniques and to determine if the pharmacoki netic parameters in the eye and CSF are similar. Twenty healthy male rabbits received intravenous fluconazole 20 mg/kg as a single dose or 20 mg/kg every 12 hours for 4 doses. Serum, aqueous humor, v itreous humor and CSF samples were taken 15 minutes after the initial intra venous injection and hourly thereafter for six hours. Fluconazole concentra tions were determined by microbiological assay. Pharmacokinetic analyses we re performed using a nonlinear least-square regression program. Fluconazole's penetration in all anatomical compartments was > 70% than in the serum. Similar elimination half-lives and time to reach maximum concent rations were noted in all compartments. While mean concentrations in each a natomical compartment were similar in animals receiving a single dose or am ong those at serum steady state, the mean concentrations achieved in the se rum, aqueous and vitreous humors and CSF were between 1.82 and 2.17 times h igher at serum steady state than following a single dose. At serum concentrations that are comparable to those in humans, the penetra tion of fluconazole into the noninflamed aqueous and vitreous humors and CS F were greater than or equal to 70%. The CSF and ocular pharmacokinetic par ameters closely resembled each other, so that either could be used as a sur rogate for the other.