Haidukewych et al developed an equation and nomogram for predicting the free phenytoin concentration in a patient being treated with both phenytoin and valproic acid. The authors are from the Epilepsy Center of Michigan in Detroit.
Basis: Phenytoin and valproic acid compete for protein binding sites. This means that the unbound concentration of phenytoin in a patient taking both drugs may be comparable to a patient taking a higher dose of phenytoin by itself.
free phenytoin concentration in µg/mL =
= (total phenytoin concentration in µg/mL) * (0.095 + (0.001 * (total valproic acid concentration in µg/mL))) =
= 0.095 * (total phenytoin concentration in µg/mL) * (1 + (0.0105 * (total valproic acid concentration in µg/mL)))
Performance:
• Kerrick et al found that this equation gave a reasonable estimate of the free phenytoin concentration but emphasized the need to actually measure the unbound fraction if possible.
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