Phenytoin: The pseudosteady‐state phenomenon

After reaching an apparent steady state, plasma phenytoin (PHT) levels may then undergo inexplicable changes, a phenomenon called “pseudosteady state”. We evaluated 13 pseudosteady‐state periods in 10 inpatients with complex partial seizures. Eleven of the periods occurred after a change in PHT dosage and two after drug withdrawal. The pseudosteady‐state period began 2 to 12 days ( X = 5.7 days) after dosage change and lasted 5 to 10 days ( X = 6.3 days), during which plasma PHT levels were stable (±5%). Plasma PHT levels thereafter fluctuated spontaneously by >25% for 5 to 22 days ( X = 10.8 days). A final steady‐state level was reached 13 to 31 days ( X =21.4 days) after the first dosage change. Falling plasma PHT levels increased seizure frequency in two patients, and a level of 52 µg/ml led to medication toxicity in another. Clinical Pharmacology and Therapeutics (1984) 35 , 822–825; doi: 10.1038/clpt.1984.119