volume of distribution<\/a>,\n occurs in conditions reducing the amount of serum albumin (such as \nhepatic failure and the nephrotic syndrome), in the presence of other \ndrugs or during the accumulation of endogenous substances competing for \nthe albumin binding sites (as in renal failure). Phenytoin crosses the \nplacenta and enters breast milk.\n<\/p>\n\n\n\nElimination occurs primarily by biotransformation to\n several inactive hydroxylated metabolites. Some of these metabolites \nare further metabolized by conjugation with glucuronic acid. Metabolites\n are then mostly excreted<\/a> in the urine. Phenytoin follows nonlinear<\/a> (or zero-order) kinetics at therapeutic concentrations, because the rate of metabolism<\/a> is close to the maximum capacity of the enzymes involved. In nonlinear kinetics, clearance<\/a> and half-life<\/a>\n fluctuate with plasma concentration. As the rate of administration \nincreases, the plasma concentration at steady state increases \ndisproportionately. If the rate of absorption equals or exceeds the \nmaximum rate of metabolism, steady state is never achieved. This \ncapacity-limited metabolism explains the interindividual variability<\/a>\n and the lack of predictability of the phenytoin plasma \nconcentration-time profile, because the maximum capacity varies from \npatient to patient. There are many conditions in which the metabolism of\n phenytoin is altered such as in hepatic cirrhosis or during the \nadministration of concomitant drugs<\/a>.<\/p>\n\n\n\nChart Pharmacokinetics<\/p>\n
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