Enteral fluconazole population pharmacokinetics in patients in the surgical intensive care unit.
OBJECTIVE
To determine the population pharmacokinetic parameters of enterally administered fluconazole in patients in a surgical intensive care unit (SICU).


METHODS
Population pharmacokinetics component of a prospective, randomized clinical study.


METHODS
The SICU at a university hospital.


METHODS
One hundred ten patients with an expected length of stay in the SICU of 3 or more days and a need for intubation, in whom at least one fluconazole plasma concentration-time measurement was available. Intervention. Patients received fluconazole as an 800-mg loading dose and as a 200- or 400-mg (depending on renal function) daily maintenance dose. Fluconazole suspension was administered enterally followed by a 30-ml free water flush.


RESULTS
Plasma samples were collected, and population pharmacokinetic analysis was performed with NONMEM software; a one-compartment pharmacokinetic model was used. Fluconazole clearance was dependent on creatinine clearance, and volume of distribution was dependent on body weight and age. In patients with creatinine clearance values greater than 80 ml/minute, between 30 and 80 ml/minute, and less than 30 ml/minute, geometric mean (percentage coefficient of variation) fluconazole clearance was 14.39 ml/minute (21%), 10.53 ml/minute (28%), and 5.47 ml/minute (30%), respectively. The geometric mean (percentage coefficient of variation) volume of distribution in all patients was 1.27 L/kg (28%) and decreased with increasing age.


CONCLUSIONS
Fluconazole clearance values in patients in the SICU who had normal renal function and in those with renal impairment were in agreement with previously reported data. Fluconazole volume of distribution was larger and half-life was longer in the SICU population than in healthy subjects.
Department of Clinical Pharmacology, Bayer Pharmaceuticals, West Haven, Connecticut, USA.
Prabhu
P
Rajagopalan
Robert K
RK
Pelz
Pamela A
PA
Lipsett
Sandra M
SM
Swoboda
Michael G
MG
Rinaldi
Craig W
CW
Hendrix
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D001835:Body Weight; D003404:Creatinine / Q000097:blood; D003422:Critical Care; D004333:Drug Administration Routes; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007362:Intensive Care Units; D007674:Kidney Diseases / Q000378:metabolism; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000517:prevention & control; D011446:Prospective Studies
D000935:Antifungal Agents; D015725:Fluconazole; D003404:Creatinine