Quantification of brain voriconazole levels in healthy adults using fluorine magnetic resonance spectroscopy.
Voriconazole is more effective for aspergillosis infections with central nervous system involvement than other antifungal agents. The clinical efficacy of voriconazole for central nervous system infections has been attributed to its ability to cross the blood-brain barrier. However, pharmacokinetic studies are limited to plasma and cerebrospinal fluid, so it remains unclear how much of the drug enters the brain. Fluorinated compounds such as voriconazole can be quantified in the brain using fluorine-19 magnetic resonance spectroscopy (MRS). Twelve healthy adult males participated in a pharmacokinetic analysis of voriconazole levels in the brain and plasma. Open-label voriconazole was dosed per clinical protocol with a loading dose of 400 mg every 12 h on day 1, followed by 200 mg every 12 h administered orally over a 3-day period. MRS was performed before and after dosing on the third day. Voriconazole levels in the brain exceeded the MIC for Aspergillus. The brain/plasma ratios were 3.0 at steady state on day 3 (predose) and 1.9 postdose. We found that voriconazole is able to penetrate the brain tissue, which can be quantified using a noninvasive MRS technique. (This study has been registered at ClinicalTrials.gov under registration no. NCT00300677.).
McLean Hospital, McLean Imaging Center, Belmont, Massachusetts, USA.
Michael E
ME
Henry
Nicolas R
NR
Bolo
Chun S
CS
Zuo
Rosemond A
RA
Villafuerte
Kenroy
K
Cayetano
Paul
P
Glue
Bharat D
BD
Damle
Emma
E
Andrews
Tara L
TL
Lauriat
Namoode S
NS
Rana
Jeffrey H
JH
Churchill
Perry F
PF
Renshaw
D000284:Administration, Oral; D000328:Adult; D000935:Antifungal Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D004334:Drug Administration Schedule; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011743:Pyrimidines / Q000097:blood / Q000493:pharmacokinetics*; D014230:Triazoles / Q000097:blood / Q000493:pharmacokinetics*; D065819:Voriconazole
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole