Relative Proportions of Serum Carbamazepine and its Pharmacologically Active 10,11-Epoxy Derivative: Effect of Polytherapy and Renal Insufficiency

Abstract

Background: The proposed action mechanism and pharmacological activity of carbamazepine (CBZ) and its major metabolite, carbamazepine-10,11-epoxide (CBZE), are the same. The aim of our study was the investigation of the effect of concomitant antiepileptic treatment and renal insufficiency on the relative proportions of serum CBZ and CBZE.

Methods: Serum trough steady-state CBZ and CBZE concentrations were determined by high-performance liquid chromatography (HPLC) in 140 epileptic patients treated with CBZ in monotherapy (n=100) and polytherapy with phenytoin, phenobarbital and valproate (n=40). The levels of CBZ were also determined using the Dade Behring enzyme multiplied immunoassay technique (EMIT). The glomerular filtration rate (GFR) was estimated from serum cystatin C using the Dade Behring nephelometric immunoassay.

Results: The CBZE/CBZ and CBZ+CBZE/CBZEMIT ratios were significantly increased in 7 cases (3 in monotherapy and 4 in polytherapy) with GFR<60 mL/min/1.73m2 in relation to the patients treated in monotherapy or polytherapy having normal or mildly decreased renal function (p<0.001).

Conclusions: In patients with moderate to severe renal insufficiency the relative proportion of CBZE with respect to the parent drug is significantly increased. In these cases, the CBZ concentrations obtained using the EMIT, or other immunoassays having low CBZE cross-reactivity, may have an inadequate diagnostic efficiency.