My fellowship director was the Great Brain, Dr Patrick Murray
. Pat is quadruple boarded:
- internal medicine
- critical care
- clinical pharmacology
Pretty intimidating. (If you have the time, check out his 179-slide presentation
One of the side effects of doing my fellowship under a professor in clinical pharmacology is that I learned more about drug monitoring in renal failure than any innocent nephrology fellow should.
One of the pearls he taught regarded the monitoring of therapeutic Dilatin (phenytoin) levels. the Renal Fellow Network discussed Dilantin pharmacokinetics
twice but neither of the posts noted the change in protein binding that occurs with renal failure.
Dilantin is highly protein bound (90%
) and only the free dilantin is therapeutically active. Uremia is associated with plasma molecules which displace Dilantin from albumin. This increases the active fraction of Dilantin, so sub-therapeutic total levels of Dilantin may represent appropriate free levels in the presence of renal failure.
I currently have a dialysis patient in the ICU who was seizing following a cardiac arrest. He was loaded with Dilantin and a few days later his labs showed:
Total phenytoin level of 5 mcg/mL, below the therapeutic target of 10-20. Simultaneously his free level was 1.14 mg/L. (Rant: How can the EMR express the total level as mcg/ml and the free level as mg/L. THEY ARE EQUIVALENT. Don't hide it.)
So in this case the free dilantin is 23% of the total, rather than the normal 10%. Note that the total level appears sub-therapeutic but this patient would be poorly served by a re-loading of Dilantin as his free level is therapeutic.
Summary: in uremia always use the free dilantin level and don't trust the total Dilantin level.