title: Carbamazepine and carbamazepine-10,11-epoxide clearance measurements during continuous venovenous hemofiltration in a massive overdose.
abstract: BACKGROUND
  Carbamazepine (CBZ) overdose can result in significant neurologic and cardiovascular toxicity, and is compounded by the presence of an active metabolite, carbamazepine-10,11-epoxide (CBZE). Existing publications describing continuous venovenous hemofiltration (CVVH) in CBZ overdose are limited in their ability to calculate accurate clearances. We report a case of CBZ overdose treated with CVVH with detailed measurement of CBZ, CBZE and their respective clearances calculated utilizing serial effluent measurements. This was coupled with serum level determinations comparing two analytical methodologies, time-of-flight mass spectroscopy and an immunoassay.
  
  
  METHODS
  A 41-year-old woman presented unresponsive after an overdose of CBZ. Initial CBZ serum levels were markedly elevated (57.8 μg/mL) and continued to rise. Due to continued hemodynamic instability, extracorporeal removal was initiated using CVVH.
  
  
  METHODS
  During the first 30 h of CVVH, interval serum samples and all ultrafiltrate bags were collected and analyzed. Serum and effluent levels of CBZ and CBZE were measured using an Agilent 6230 time-of-flight high-resolution mass spectrometer (TOF-MS). CBZ levels were also obtained utilizing the Microgenics CEDIA Carbamazepine Immunoassay (Thermo Fisher, Waltham, MA) for serum and effluent samples. Immunoassay analysis was performed using Siemens ADVIA 1800 instrument.
  
  
  RESULTS
  The clearances achieved for CBZE (mean = 25.2, range 17.7-42.6 mL/min) exceeded that for CBZ (mean = 18.1, range 12.7-28.7 mL/min). CVVH removed a total of 1293 and 1261 mg of CBZ and CBZE, respectively. Serum levels of CBZ measured by immunoassay when compared with TOF-MS indicated cross reactivity of CBZE with the immunoassay.
  
  
  CONCLUSIONS
  CVVH removed CBZE with higher clearances than CBZ. However, CVVH clearance rates for both CBZ and CBZE were lower than published clearances of CBZ and CBZE by intermittent hemodialysis. Our methodology allowed for a precise pharmacokinetic assessment of clearance based on total quantity of parent drug and active metabolite removed. Use of an immunoassay to determine CBZ serum levels reflects both parent compound and active metabolite due to cross-reactivity with CBZE.
authors.affiliation: a Department of Emergency Medicine , University of California San Francisco , San Francisco , CA , USA ;
authors.forename: Craig Geoffrey
authors.initials: CG
authors.lastname: Smollin
authors.affiliation: b TPMG Regional Laboratories , Berkeley , CA , USA ;
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Petrie
authors.affiliation: c School of Pharmacy , University of California San Francisco , San Francisco , CA , USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kearney
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000097:blood* / Q000506:poisoning; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000097:blood* / Q000506:poisoning; D002851:Chromatography, High Pressure Liquid; D062787:Drug Overdose / Q000097:blood* / Q000628:therapy; D005260:Female; D006440:Hemofiltration / Q000379:methods*; D006801:Humans; D008657:Metabolic Clearance Rate; D006435:Renal Dialysis; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; C012227:carbamazepine epoxide
keywords: Carbamazepine-10,11 epoxide; hemodialysis; overdose; poisoning