THERAPEUTIC DRUG-MONITORING OF PHENYTOIN IN PATIENTS WITH THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME

Serum phenytoin concentrations were investigated in 109 serum samples from 21 patients with the acquired immunodeficiency syndrome (AIDS) and in 1,231 serum samples from 557 control subjects during phenytoin therapy. Total phenytoin concentrations were significantly lower in patients with AIDS than in the reference population (8.8 +/- 0.7 mg/L (mean +/- SE) vs. 10.6 +/- 0.2 mg/L), although phenytoin doses were significantly higher in the AIDS patients. Body weight and the use of folic acid were negatively related to phenytoin concentrations, whereas use of clarithromycin resulted in higher phenytoin levels. Zidovudine did not influence phenytoin levels. Calculation of the Michaelis-Menten parameters showed that V-max values were similar in seven human immunodeficiency virus (HIV)-infected patients as compared with 12 controls, but a nonsignificant trend of lower K-m values in the HIV-positive group was observed. Measurement of free phenytoin concentrations demonstrated that the fraction of unbound drug was increased in patients with AIDS. Hypoalbuminemia was common in this population, which may complicate the interpretation of total phenytoin concentrations.