Therapeutic Drug Monitoring of Antiepileptic Drugs in Real Clinical Practice in Russia

Abstract

Leonova Marina V, Shteinberg Lyudmila L, Tischenkova Irina F

Introduction: Anticonvulsants refer to drugs with interindividual variability of plasma concentrations and clinical efficacy. Therapeutic drug monitoring (TDM) is an important tool for optimizing pharmacotherapy with anticonvulsants in real clinical practice. The aim of the study was to analyze the results of TDM of valproates (VPA) and carbamazepine (CBZ) in epilepsy adults in clinical practice in Russia.

Methods: observation study in 800 epilepsy adults (mean age 35.5±0.5) the rate of achievement the therapeutic concentrations (TC) of VPA and CBZ in different drug forms using high performance liquid chromatography; range of TC for VPA 50-150 mg/l, for CBZ 4-12 mg/l.

Results: The frequency of achievement TC on VPA was 66.4% in average dose – 1325.1±29.6 mg/day with no difference between sustain-released and immediate-released drug forms. Gender differences of VPA concentrations were identified: women mean Cmin and Cmax were higher than in men with significantly lower daily dose. The frequency of sub-TC VPA was 16.3% and over-TC – 1% (Cmax 164.2±2.4mg/l); the toxic concentration for CNS (175 mg/l) was not achieved. In VPA doses<500mg/day there was no patients with TC; in 1001–1500 mg/day TC have 75%, in doses 1501–2000mg/day – 97%; in >2000 mg/day – 86% and there was high risk of over-TC (4%). The frequency of achievement TC range VPA monotherapy was 2 times more than in combination VPA+CBZ (67% versus 34%). The frequency of achievement TC range on CBZ was 78.6%, the average daily dose was 922.2±23.0 mg/day with significantly higher rate of TC range achievement when using sustain-release forms of CBZ. The frequency of sub-TC CBZ was 6.3%, over-TC – 1.25%. In patients with over-TC mean dose was 1250 mg/day, Cmin 13.5±0.2mg/l, Cmax 15.1±0.7mg/l. At initial doses<600 mg/day 64.3% patients have TC; in doses>600 mg/day – 87%. In daily doses 600-1200 mg and >1200 mg 1.3% and 4.1% patients have over-TC by both Cmin and Cmax, only by Cmax – 8.8% and 18.4%, respectively.

Conclusion: the frequency of TC on VPA and CBZ is high with rare cases of over-TC, but there was problem of paradox low concentrations in single cases. CBZ have less predictable concentrations in therapeutic doses range than VPA.

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