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Filtration for free drug level monitoring: carbamazepine and valproic acid

Filtration for free drug level monitoring: carbamazepine and valproic acid

Therapeutic Drug Monitoring 6(1): 67-76

Free carbamazepine and valproic acid monitoring using the EMIT FreeLevel filtration system was evaluated and compared with reference equilibrium dialysis and gas chromatographic (GC) techniques. For carbamazepine, free levels after filtration or dialysis were essentially identical (mean 1.74 vs. 1.77 mg/L, r = 0.940, n = 28, EMIT assay). Free levels were 16% higher by EMIT than by GC, possibly due to cross-reaction with carbamazepine-10,11-epoxide. Free fractions were not significantly different using any combination of filtration or dialysis with EMIT or GC (means 0.24-0.26). There was a significant correlation between epoxide and parent-drug free fractions (r = 0.642). Free fraction varied from 0.20 to 0.41 among 61 patient samples and was independent of total drug concentration. For valproic acid, there was a strong correlation between filtration and dialysis results for free level (r = 0.974) and free fraction (r = 0.892), but filtration values were 6-7% higher. Free fraction was concentration dependent (r = 0.597), and lower free fractions by dialysis were attributed to dilution of total drug concentration. Free fraction varied from 0.01 to 0.14 among 50 patient samples. For carbamazepine and valproic acid the EMIT FreeLevel filtration system compared favorably with equilibrium dialysis, and had the advantage of being rapid.

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Accession: 043128277

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PMID: 6424279

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