1. Vozeh-Sheiner or Orbit Graph employing Bayesian feedback used to estimate Michaelis-Menten parameters and phenytoin dose using one steady-state dose/concentration pair (example 7 data shown). The orbs represent 50%, 75%, 85%, etc of the population parameter combinations for Vmax and Km. The drug dose is converted into a phenytoin amount (in mg/kg/d) and plotted on the y-axis (circle, 4.9 mg/kg/d). The concurrent steady-state phenytoin serum concentration is plotted on the left portion of the x-axis (circle, 6.2 μg/mL), and the two points are joined with a straight line across the orbs. If the line intersects more than one orb, the innermost orb is selected, and the midpoint of the line contained within that orb is found and marked (x mark within orbs). The new desired steady-state concentration is identified on the left portion of the x-axis (x mark on x-axis, 10 μg/mL), and the two x marks are connected by a straight line. The required phenytoin dose is identified at the intersection of the drawn line and the y-axis (5.5 mg/kg/d). If necessary, the dose would be converted to phenytoin sodium or fosphenytoin amounts. Estimates ofVmax (7.9 mg/kg/d) and Km (4 μg/mL) are obtained by extrapolating parallel lines to the y- and x-axes, respectively.
Source: Phenytoin/Fosphenytoin, Applied Clinical Pharmacokinetics, 3e
Citation: Bauer LA. Applied Clinical Pharmacokinetics, 3e; 2015 Available at: Accessed: October 10, 2017
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