Multiple Oral Doses

Linear Plot of Cp versus time



Comments

Metabolism can be subject to a number of factors, such as genetics, disease state and co-administration of other compounds. Other compounds may inhibit metabolism or induce metabolic activity. Some drugs are capable of inducing their own metabolism.

Carbamazepine is a drug which can induce its own metabolism during the first few days of therapy (Hawkins Van Tyle and Winter, 2004). After the first dose, carbamazepine pharmacokinetic parameters include F = 0.8, V = 1.4 L/Kg, CL = 0.028 L/Kg/hr. After 3 to 5 days carbamazepine metabolism is induced such that the CL becomes 0.064 L/Kg/gr. For a 70 Kg patients pre-induction (first-dose) parameter values are kel = 0.02 hr-1 and V = 100 L. After induction the kel changes to 0.045 hr-1. Dose adjustment during the first few days can be difficult. Using post induction parameters for initial dosage regimen could cause toxic concentrations. For example, try the simulation again with a dose regimen of 600 mg every 12 hours with both pre and post induction kel values. The typical therapeutic plasma concentration range is 4 - 12 mg/L.


References


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