Drugs with saturable, Michaelis–Menten elimination — phenytoin is the classic example, and caffeine and ethanol in overdose — behave differently once concentrations approach the Km. Above it, clearance is capped, so a small dose increase can produce a disproportionately large rise in level and a much longer time to fall. For phenytoin, increase maintenance doses in small steps (often 25–50 mg), recheck the level after a longer interval, and remember that low albumin raises the free fraction.
- Increase phenytoin doses in small increments once levels are near the therapeutic range.
- Allow longer than the usual five half-lives before rechecking — steady state takes longer at higher levels.
- Correct phenytoin levels for low albumin or measure free phenytoin.
- In overdose of saturable drugs, expect prolonged toxicity.
Why it matters
Linear-kinetics intuition causes predictable toxicity with these drugs.
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