Determination of the unbound fraction of R- and S-methadone in human brain

Excerpt

We read with interest the article by Holm and Linnet [1], entitled “Determination of the unbound fraction of R- and S-methadone in human brain” in the International Journal of Legal Medicine. Based on the free drug hypothesis that only the unbound fraction (fu) of a given drug is biologically available in terms of its pharmacological activity, Holm and Linnet examined whether isolating the unbound fraction of the active R-methadone enantiomer from brain matter could be of value as a forensic tool. They found no overall correlation between the active R-methadone concentration and fu were found. Small but statistically significant differences in median fu for the R-methadone enantiomer were identified between case-categories (i.e., poisoning with multiple drugs, methadone poisoning, and deaths unrelated to methadone), but these are thought to be too low to be of any forensic value [1]. …