Predicting unbound phenytoin concentrations in the critically ill neurosurgical patient.
OBJECTIVE
To assess the correlation of measured unbound phenytoin concentration (dphF) to estimated unbound concentration (dphEF) using the Sheiner-Tozer equation in critically ill patients in the neurosurgical intensive care unit.


METHODS
The dphF and total phenytoin (dphT) trough serum concentrations were measured during the first week of therapy in 17 consecutive patients with albumin concentrations less than 3.5 g/dL. Serum albumin concentrations were measured within 24 hours of serum phenytoin concentration measurement.


METHODS
A university-affiliated urban teaching hospital.


METHODS
The study population consisted of 17 neurosurgical patients who were at least 18 years old.


METHODS
The predictability of the Sheiner-Tozer equation was tested by measuring dphF, dphT, and serum albumin concentrations. Measured phenytoin concentrations were compared with phenytoin concentrations calculated from the Sheiner-Tozer equation. To estimate correlation between variables linear regression was calculated. Mean absolute value of error and mean error were estimated to assess precision and bias between measures, respectively.


RESULTS
The mean +/- SD dphT was 13.05 +/- 5.15 mu g/mL. The measured dphF was 1.89 +/- 0.80 compared with 2.00 +/- 0.8 mu g/mL for the dphEF (NS). Regression analysis for dphEF versus dphF revealed a significant correlation (r2 = 0.94, p = 0.001). The mean absolute value of error for the Sheiner-Tozer equation to predict dphEF was 0.167, which was 9% of the mean value of dphEF (1.89).


CONCLUSIONS
These results indicate that, in this population, the Sheiner-Tozer estimate of dphEF provides an unbiased, precise clinical estimate of dphF in patients for whom measured dphF is unavailable or impractical.
Mlynarek
M E
ME
Henry Ford Hospital, College of Pharmacy, Detroit, MI, USA.
Peterson
E L
EL
Zarowitz
B J
BJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016638:Critical Illness; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008433:Mathematics; D008875:Middle Aged; D009493:Neurosurgery; D010672:Phenytoin / Q000097:blood* / Q000493:pharmacokinetics; D011184:Postoperative Period; D012709:Serum Albumin / Q000032:analysis*
D012709:Serum Albumin; D010672:Phenytoin