Garfinkel D, Mamelok R D, Blaschke T F
Ann Intern Med. 1987 Jul;107(1):48-50. doi: 10.7326/0003-4819-107-1-48.
Although most assays for measuring drug levels in serum determine the total concentration, effects from a drug are determined better by measuring the concentration of unbound (free) drug in serum. When the free fraction of a drug is constant, the total drug concentration may act as a good guide in predicting drug activity. However, if the free fraction is altered from normal, the serum concentration of the total drug may be misinterpreted. Quinidine has a high binding affinity for alpha-1-acid glycoprotein. We present the case of a woman who had a myocardial infarction; after cardiac surgery, she was found to have high concentrations of alpha-1-acid glycoprotein (228 mg/dL) and a low free fraction of quinidine (0.032). At that time the patient had a total concentration of quinidine of 33.9 mumol/L (11 micrograms/mL) but showed no signs or symptoms of toxicity because the concentration of free quinidine was not high. Physicians should be aware of the limitations of assays in determining the unbound concentration of drugs in serum. This awareness is particularly crucial with drugs that bind well to serum proteins, especially when pathologic conditions change the extent of binding.
