steady-state blood levels after every dosage change;at higher levels,it may be 4-6 weeks before blood levels are stable. 口 30 20 10 0 200 400 600 800 Phenytoin dosage(mg/d) Figure 24-3.Nonlinear relationship of phenytoin dosage and plasma concentrations. Five different patients(identified by different symbols)received increasing dosages of phenytoin by mouth,and the steady-state serum concentration was measured at each dosage.The curves are not linear,since,as the dosage increases,the metabolism is saturable.Note also the marked variation among patients in the serum levels achieved at any dosage.(Modified,with permission,from Jusko WJ:Bioavailability and disposition kinetics of phenytoin in man.In:Kellaway P,Peterson I [editors]: Quantitative Analytic Studies in Epilepsy.Raven Press,1977.) Therapeutic Levels Dosage The therapeutic plasma level of phenytoin for most patients is between 10 and 20 mcg/mL.A loading dose can be given either orally or intravenously;the latter,using fosphenytoin,is the method of choice for convulsive status epilepticus (discussed later).When oral therapy is started,it is common to begin adults at a dosage of 300 mg/d,regardless of body weight.This may be acceptable in some patients,but it frequently yields steady-state blood levels below 10 mcg/mL,which is the minimum therapeutic level for most patients.If seizures continue,higher doses are usually necessary to achieve plasma levels in the upper therapeutic range.Because of its dose-dependent kinetics,some toxicity may occur with only small increments in dosage.The phenytoin dosage should be increased each time by only 25-30 mg in adults,and ample time should be allowed for the new steady state to be achieved before further increasing the dosage.A common clinical error is to increase the dosage directly from 300 mg/d to 400 mg/d;toxicity frequently occurs at a variable time thereafter.In children,a dosage of 5 mg/kg/d should be followed by readjustment after steady-state plasma levels are obtained.steady-state blood levels after every dosage change; at higher levels, it may be 4-6 weeks before blood levels are stable. Figure 24-3. Nonlinear relationship of phenytoin dosage and plasma concentrations. Five different patients (identified by different symbols) received increasing dosages of phenytoin by mouth, and the steady-state serum concentration was measured at each dosage. The curves are not linear, since, as the dosage increases, the metabolism is saturable. Note also the marked variation among patients in the serum levels achieved at any dosage. (Modified, with permission, from Jusko WJ: Bioavailability and disposition kinetics of phenytoin in man. In: Kellaway P, Peterson I [editors]: Quantitative Analytic Studies in Epilepsy. Raven Press, 1977.) Therapeutic Levels & Dosage The therapeutic plasma level of phenytoin for most patients is between 10 and 20 mcg/mL. A loading dose can be given either orally or intravenously; the latter, using fosphenytoin, is the method of choice for convulsive status epilepticus (discussed later). When oral therapy is started, it is common to begin adults at a dosage of 300 mg/d, regardless of body weight. This may be acceptable in some patients, but it frequently yields steady-state blood levels below 10 mcg/mL, which is the minimum therapeutic level for most patients. If seizures continue, higher doses are usually necessary to achieve plasma levels in the upper therapeutic range. Because of its dose-dependent kinetics, some toxicity may occur with only small increments in dosage. The phenytoin dosage should be increased each time by only 25-30 mg in adults, and ample time should be allowed for the new steady state to be achieved before further increasing the dosage. A common clinical error is to increase the dosage directly from 300 mg/d to 400 mg/d; toxicity frequently occurs at a variable time thereafter. In children, a dosage of 5 mg/kg/d should be followed by readjustment after steady-state plasma levels are obtained