Question

Calculation problem 4: nonlinear PK, phenytoin dosing A 70-kg patient has been taking phenytoin 250 mg per day for 4 months. His plasma drug level averaged 5 mg/L on this dose. Adjustment in dose to 500 mg per day eventually led to a new plateau level of 25 mg/L. The volume of distribution of phenytoin is 0.65 L/kg. 1) Use a graphical method to estimate the patient's Vma/F and K values. 2) Estimate a daily dose which should provide a steady-state plasma level of 15 mg/L 3) Estimate the steady-state plasma level at a daily dose of 400 mg and the time required to achieve 90% of the steady-state plasma leve 4

Answer 1

.A 70 kg patient has been taking phenytoin 250mg per day for 4 months. His plasma drug level averaged 5mg/l on this dose. Adjustment in dose to 500mg per day eventually led to a new plateau level of 25mg/L. The volume of distribution of phenytoin is 0.65l/kg

1.

.

Too 6 oD 5D0 OD 300 200 g. l 00

Here the V_max = 666.6 mg/day of phenytoin

K_m = 8.3 mg/L

2.

mhn Sone on n 七 , (C2-6)

125000x 20 315 0 RS-00000 3150 = 666.6 2 S o 083-6. S 3

Here the V_max = 666.6 mg/day of phenytoin

K_m = 8.3 mg/L

Therefore

666.6 x1s 8.3+IS 2 3 3

Thus we can say that the daily dose of phenytoin which should provide a which should provide a steady-state plasma level of 15mg/L is 429mg/day