Valproic Acid drug monitoring

A competitive fluorescence-polarization immunoassay method was described for the monitoring of 12 drugs including valproic acid [18]. Samples (serum or plasma) were deproteinated. Fluorescence from the fluorescein-labeled analyte used as tracer was excited at 488 nm and polarization of light emitted at 531 nm was measured. The calibration was stable for 4 weeks and the coefficient of variation was below 10%. A single measurement took 8-10 min. 

Unlike carbamazepine, valproic acid has few drug interactions, an added benefit for elderly patients. One interaction worthy of mention, however, is that aspirin can increase levels of valproic acid. For this reason, vascular dementia patients taking an aspirin a day may need a lower dose of valproic acid or at least more careful monitoring of blood levels when starting valproic acid. 

The Depakote form of valproic acid is approved for the acute phase of bipolar disorder. It is also commonly used on a long-term basis, although its prophylactic effects have not been as well established. Valproic acid is now frequently used as a first-line treatment for bipolar disorders, as well as in combination with lithium for patients refractory to lithium monotherapy and especially for patients with rapid cycling and mixed episodes. Oral loading can lead to rapid stabilization, and plasma levels must be monitored to keep drug levels within the therapeutic range. 

Serious drug interactions are uncommon with valproate. Approximately 25% of valproate metabolism is dependent on CYP isoenzymes. Valproic acid can cause severe liver damage during the first 6 months of treatment. Note interactions with aspirin and the need to monitor plasma free valproate levels. 

The rationale and use of modified-release formulations of antiepileptic drugs (carbamazepine, valproic acid, and tiagabine) have been reviewed (171). The authors concluded that modified-release formulations afford the advantages of better patient compliance, fewer adverse effects, and less fluctuation in plasma concentrations, making monitoring of drug concentrations easier. They concluded that these advantages should lead to better seizure control and improved quahty of life. 

Gatti, G., Crema, F., Attardo-Parrinello, G., Fratino, P, Aguzzi, F., and Perucca, E., Serum protein binding of phenytoin and valproic acid in insulin-dependent diabetes mellitus, Then Drug Monitor., 9, 389, 1987. 

Corti, P. Cenni, A. Corbini, G. Dreassi, E. Murratzu, C. Caricchia, A.M. Thin-layer chromatography and densitometry in drug assay comparison of methods for monitoring valproic acid in plasma. J.Pharm.Biomed.Anal., 1990, 8, 431-436... 

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