ISSN:
1573-8744
Keywords:
phenytoin
;
dosage regimen design
;
Michaelis-Menten pharmacokinetics
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Computer simulations were performed using a one-compartment open model with either first-order or zero-order input and either Michaelis-Menten or Michaelis-Menten and first-order elimination. Twelve theoretical cases constructed from various combinations of typical and atypical values for phenytoin pharmacokinetic parameters, V max and K m , were examined. In many cases, at least 90% of the eventual steady-state serum level would be achieved within 4 weeks when phenytoin was administered at an appropriate rate. In the case of a low-to-average Vmax value and an average-to-high Km value, an initial maintenance dose of 3–4 mg phenytoin sodium/kg/day would, within a few days, result in serum phenytoin levels above the usual therapeutic range. On the other hand, if V max and K m values were both low (3.8 mg/kg/day and 1.45 mg/liter, respectively), a very slow rate of accumulation would ensue. Thirty days after the start of 4 mg phenytoin sodium/kg/day, a serum level of about 16 μg/ml would likely occur. The magnitude of continued accumulation beyond this level would be significantly influenced by the rate of renal elimination of unchanged phenytoin. It is recommended that, after initiation or adjustment of phenytoin therapy, serum phenytoin levels be monitored weekly for 3–4 weeks, then monthly for 2 additional months. Long-term follow-up should include serum phenytoin levels every 3– 6 months or as clinically indicated. Appreciation of the characteristics of phenytoin accumulation in relation to rate of administration and individual pharmacokinetic parameters is important for accurate interpretation of serum phenytoin levels and rational adjustment of dosage regimens.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01062722
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