Pharmacokinetic Phenytoin Problems

Questions provided by Michele Splinter, PharmD


Question 1. Determine an intravenous loading dose of phenytoin sodium injection for MA, 5'9", 89 Kg female, using a volume of distribution of 0.65 L/Kg and a desired level of 21 mg/L. Round to the nearest multiple of 50 mg. (1 point)


Question 2. Determine a daily maintenance dose of oral phenytoin sodium capsules for MA using a Vmax of 1.79 mg/kg/day, Km of 2.3 mg/L, Css = 17 mg/L. Round to the nearest dose using available phenytoin sodium capsules to determine a daily dose for MA. (1 point)


Question 3. A 18 year-old, 6'2", 90 kg female had been receiving 450 mg phenytoin chewable tablets daily for 2 weeks and her trough plasma concentration was 8.4 mg/L. Her dose was increased to 300 mg twice a day and now two weeks later her phenytoin level is 20.7 mg/L. (3 x 0.5 points)

a. Calculate the patient-specific Km.

b. Calculate the patient-specific Vmax

c. Calculate the new maintenance daily dose of phenytoin chewable tablets with a desired Cpss of 18 mg/L using both patient-specific Vmax and Km.


Question 4. A female patient with generalized tonic-clonic seizures attained a steady state serum concentration of 12 mg/L on 430 mg daily of Dilantin® kapseals. She was transferred to a rehabilitation hospital and received 500 mg Dilantin® kapseals. Two weeks later she as noted to have ataxia and a new level was 20 mg/L.

a. Calculate Km and Vmax using the graphical method of Mullen. (2 x 0.25 points)

b. Calculate the new dose per day to produce 16 mg/ml. (0.5 points)

c. Using the regression method of Ludden, determine Vmax and Km. (2 x 0.25 points)

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Some Equations:

IBW equation (male)
Equation 31.2.1 IBW for Male Patients

IBW equation (female)
Equation 31.2.2 IBW for Female Patients

Vd for Obese patient
Equation 31.2.3 Vd for Obese Patients (i.e. Actual Body Weight > 120% of Ideal Body Weight)

Loading Dose
Equation 31.2.4 Loading Dose

Dose Rate
Equation 31.2.5 Dose Rate

Km Patient Specific
Equation 31.2.6 Patient Specific Km

Patient Specific Vm
Equation 31.2.7 Patient Specific Vm

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