Ms. Monaghan et al., Correlation and prediction of phenytoin protein binding using standard laboratory parameters in patients after renal transplantation, THER DRUG M, 23(3), 2001, pp. 263-267
Renal transplant recipients provide a unique model for protein-binding stud
ies in that patients experience hypoalbuminemia and renal dysfunction, both
of which alter protein binding. The purposes of this investigation were to
model the relationship between serum creatinine, blood urea nitrogen (BUN)
, albumin, and the unbound fraction of phenytoin (FU, as a percentage) in p
atients who had undergone renal transplant, and to determine the value of t
hese measurements in predicting FU. Blood from 29 patients was collected at
various time points after establishment of graft function. Sera were spike
d with phenytoin to a concentration of 15 mg/L, and total/unbound phenytoin
concentrations were determined. Correlations between FU and the biochemica
l indices of serum creatinine, BUN, and albumin were determined using multi
ple regression. The algorithm with the highest correlation at all times aft
er the transplant became the method to predict future FU. This algorithm wa
s applied prospectively in 23 samples from 14 other patients with variable
renal function after transplant. Samples were analyzed as above and the cor
responding biochemical indices of serum creatinine, BUN, and albumin were u
sed to calculate FU values. Accuracy of the predictions was evaluated using
prediction-error analysis. The best relationship between FU and the measur
ed biochemical indices incorporated serum creatinine and albumin [y = 24.3
+ 0.6(serum creatinine) - 3.9(albumin)] and served as the method for FU pre
diction. Prediction-error analysis resulted in a bias of -5.1% and a precis
ion of 5.7%. This method failed to estimate FU with sufficient accuracy to
permit clinical utility. The predicted value underestimated the measured va
lue, and some other variable(s) must be affecting the binding even though s
erum creatinine and albumin are within or approaching the reference range.
Consequently, estimating FU in patients with a history of uremia and hypoal
buminemia, based on measures of serum creatinine and albumin alone, should
not be used.