Читать книгу Clinical Pharmacology and Therapeutics - Группа авторов - Страница 51

There are two possibilities: the dose was too low, or she was not adhering to her prescribed dose. As patients generally require phenytoin maintenance doses in the range 4.5–5 mg/kg/day, both doses were higher than average. Phenytoin has non‐linear pharmacokinetics at concentrations normally seen clinically, and standard pharmacokinetic equations cannot be used. The relationship between dose rate and average steady‐state concentration is controlled by V_max (the maximum amount of drug that can be metabolised by the enzymes per day) and K_m (the concentration at half V_max). Using average values of V_max (7.2 mg/kg/day) and K_m (4.4 mg/L), Mrs D.L.'s expected concentration can be calculated from the Michaelis–Menten equation:

The measured concentration of 6 mg/L is much lower than expected and suggests poor adherence with therapy.