May 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 Gesellschaft fur Epilepsieforschung in Bielefeld, Germany.
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) * (0.0792 + (0.000636 * (total valproic acid concentration in µg/mL))) =
= 0.0792 * (total phenytoin concentration in µg/mL) * (1 + (0.00803 * (total valproic acid concentration in µg/mL)))
Performance:
• Kerrick et al found that this equation underestimated the true unbound phenytoin concentration by around 0.5 µg/mL at unbound levels around 2.0 µg/mL.
• Adjusting the numerical factors could improve performance.
• Variation in analytical methods might be able to explain some of the performance issues.
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