LETTER TO THE EDITOR |
Charles E. Ahlfors, MD
LW Ligand, LLC
Vashon, WA 98070-3609
| The first 20% of the full text of this article appears below. |
To the Editor.
The commentary by McDonagh and Maisels1 in response to our recent review2 opens with an assertion that "changes in plasma concentrations of free drug are thought to have little clinical relevance except in unusual situations," implying that measurement of unbound (free) unconjugated bilirubin (Bf) is unlikely to be useful in evaluating risk for bilirubin encephalopathy. We suggest that this reflects a misinterpretation of the cited articles,35 which describe pharmacokinetic mechanisms of drug (or, in our case, bilirubin) distribution. In fact, Benet and Hoener3 clearly state that "pharmacologic effect is related to unbound drug concentration." Evidence that brain uptake of bilirubin is primarily determined by Bf was recently presented by Ahlfors and Parker6 on the basis of measured Bf and dissociation rates of protein-bilirubin complexes in jaundiced infants sera.
We agree with the cited articles that the quality of serum binding normally has little influence on the pharmacologic response to