Pharmacokinetic studies of fluconazole in rabbits characterizing doses which achieve peak levels in serum and area under the concentration-time curve values which mimic those of high-dose fluconazole in humans.
We conducted steady-state pharmacokinetic studies with high-dose fluconazole with rabbits and human volunteers. We then derived mathematical equations that predict the doses of fluconazole that should be given to rabbits to produce 24-h area under the concentration-time curve values and maximum concentrations in serum that are similar to those measured for humans given 800 to 2,000 mg of fluconazole per day. These equations provide a rational basis for designing future efficacy studies with rabbits and in evaluating the strength with which results of previously conducted studies using rabbit infection models can be extrapolated to the clinic.
Louie
A
A
Division of Infectious Diseases, Albany Medical College, New York 12208, USA.
Liu
Q F
QF
Drusano
G L
GL
Liu
W
W
Mayers
M
M
Anaissie
E
E
Miller
M H
MH
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D015725:Fluconazole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D011817:Rabbits
D000935:Antifungal Agents; D015725:Fluconazole