Carbamazepine measurement in samples from the emergency room

The measurement of carbamazepine (CBZ) in samples from the emergency room (ER) raises several issues for drug monitoring. First, the ER frequently requires rapid turnaround time for clinical samples; this need may be more conveniently met by automated immunoassays than by high-performance liquid chromatography (HPLC), the other major analytical technique for measurement of carbamazepine. On the other hand, immunoassays often do not completely measure the pharmacologically active carbamazepine epoxide metabolite and therefore may not indicate the full extent of serum anticonvulsant activity. Second, patients may be admitted to the ER specifically because of seizure activity, which may be an indication of underor overmedication with carbamazepine and which, if due in large part to high levels of the epoxide metabolite, may not be fully assessed by immunoassay. We examined the results of carbamazepine determination in 102 consecutive samples sent from an ER. Each sample was analyzed by a fluorescence polarization immunoassay (FPIA) and by HPLC. There were good correlations between the FPIA and the HPLC for the parent drug and for the sum of the parent drug plus metabolite (carbamazepine-10,11-epoxide, CBZ-E) with these regression equations: FPIA =1.13 (HPLC CBZ) + 0.09 (r² = 0.93) and FPIA = 0.93 (HPLC CBZ + CBZ-E) – 0.55 (r² = 0.89), respectively. There were weak correlations between the FPIA and the epoxide and between the parent drug and the epoxide. Based on the FPIA and HPLC results, we classified each value relative to the therapeutic range, i.e., supratherapeutic, subtherapeutic, or therapeutic. The FPIA result agreed with the HPLC result in 10 of 11 supratherapeutic levels, 14 of 17 subtherapeutic levels, and 69 of 74 therapeutic levels. Where there was a difference in classification, the results tended to fall around the cutoff point for one or the other method. To address the possibility of elevated epoxide levels as a cause of seizure-producing toxicity, we studied 45 patients with recent seizure activity. Of them, 12 had modest elevation of the epoxide, and in six of these cases the sum of the parent drug plus epoxide was elevated above the therapeutic range for HPLC. In five cases, the FPIA indicated a supratherapeutic value. We did not observe a patient with an elevated epoxide level where the FPIA gave a seriously misleading value. We conclude that the FPIA provides an adequate measurement of carbamazepine level in the majority of patients from the ER.