Phenytoin: The pseudosteady-state phenomenon

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Abstract
After reaching an apparent steady state, plasma phenytoin (PHT) levels may then undergo inexplicable changes, a phenomenon called pseudosteady state. Thirteen pseudosteady-state periods in 10 inpatients with complex partial seizures were evaluated. Eleven of the periods occurred after a change in PHT dosage and 2 after drug withdrawal. The pseudosteady-state period began 2-12 days (.hivin.X = 5.7 days) after dosage change and lasted 5-10 days (.hivin.X = 6.3 days), during which plasma PHT levels were stable (.+-. 5%). Plasma PHT levels thereafter fluctuated spontaneously by > 25% for 5-22 days (.hivin.X = 10.8 days). A final steady-state level was reached 13-31 days (.hivin.X = 21.4 days) after the first dosage change. Falling plasma PHT levels increased seizure frequency in 2 patients, and a level of 52 .mu.g/ml led to a medication toxicity in another.