A new approach to establishing individualized maintenance doses of XXXX .

@entity3174 @entity29597 @entity2231
A new method for arriving at individualized doses of @entity3174 ( @entity29597 ) is described. This method, designated the @entity2231 method, operates on two measurements of unbound plasma @entity29597 . One plasma sample is collected 48 h after a single, oral @entity29597 dose (approximately 4.5 mg/kg). From the single dose, single sample measurements of plasma unbound @entity29597 individual estimates of intrinsic unbound @entity29597 clearance (CLuint) can be made. With the use of CLuint and weight-adjusted mean population values of Vmax predicted plasma concentrations of unbound @entity29597 for 11 subjects exhibited a mean prediction error (mpe) of 0.07 mg/L with 95% confidence limits of -0.11 to 0.26 mg/L and an error coefficient of variation [root mean squared error (rmse)/mean unbound concentration at steady state (Cuss)] of 0.4. The second plasma unbound @entity29597 is collected at steady state. From CLuint and one Cuss measurement, Vmax and Km can be directly calculated. Doses calculated by the @entity2231 method to produce plasma unbound @entity29597 concentrations of approximately 1.0 mg/L were identical to those calculated by the Bayesian method to yield plasma total @entity29597 concentrations of approximately 10 mg/L. When those doses were administered to six subjects, the plasma unbound @entity29597 concentrations predicted by the @entity2231 method exhibited a mpe of -0.13 mg/L, with 95% confidence limits ranging from -0.33 to 0.06 mg/L and an error coefficient of variation of 0.2. The plasma @entity29597 concentrations predicted by the Bayesian method exhibited an mpe of -1.30 mg/L, with 95% confidence limits of -4.02 to 1.42 mg/L and an error coefficient of variation of 0.3. Values of Vmax and doses of @entity29597 calculated to produce a Cuss of 1.0 mg/L calculated by the @entity2231 method were nearly identical to Vmax values and doses of @entity29597 calculated by Bayesian double feedback (based on two different Css values) to produce a Css of 10.0 mg/L.
