Carbamazepine and Carbamazepine-10,11-epoxide Pharmacokinetics in an Overdose Patient

Patsalos, Philip N.; Krishna, S.; Elyas, A.A.; Lascelles, P. T.

doi:10.1177/096032718700600312

Cited by 23 publications

(5 citation statements)

References 13 publications

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“…Metabolism is predominantly by first‐order hepatic elimination, with less than 3% excreted unchanged renally. Forty per cent of CBZ is converted to the active metabolite CBZ‐10,11‐epoxide, which has lower protein binding and a shorter t 1/2 (5–10 h) than the parent compound 5,7,8 . Both CBZ and CBZ‐10,11‐epoxide are measured by standard Enzyme Multiplied Immunoassay Test (EMIT) plasma assays and can result in falsely elevated plasma CBZ concentrations.…”

Section: Discussionmentioning

confidence: 99%

Massive overdose with controlled‐release carbamazepine resulting in delayed peak serum concentrations and life‐threatening toxicity

2002

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Introduction: Peak serum levels following overdose with immediate‐release formulations of carbamazepine have been reported to occur up to 2 days postingestion. We report a case of poisoning with carbamazepine controlled‐release resulting in peak levels 96 h postingestion. Case Reports: A 31‐year‐old female presented following a suspected polypharmacy overdose. She was haemodynamically stable with a Glasgow Coma Scale score of 3 and was endotracheally intubated in the emergency department. A single‐dose of activated charcoal was administered on admission and her neurological status improved gradually. Results of qualitative urine drug screen available 24 h postadmission to the intensive care department revealed benzodiazepines and carbamazepine. The serum carbamazepine concentration at this time was 66 µmol/L (therapeutic 17–42 µmol/L). A history of therapy with controlled‐release carbamazepine was discovered. Repeat‐dose activated charcoal and whole‐bowel irrigation were commenced, but poorly tolerated. Serum carbamazepine levels continued to rise and gastrointestinal tract decontamination was ceased due to the presence of an ileus. By day 4, the serum carbamazepine concentration peaked at 196 µmol/L. This was associated with coma, generalized intermittent seizure activity and hypotension. Charcoal haemoperfusion was commenced due the presence of end‐organ toxicity and failed gastrointestinal tract decontamination. Serum carbamazepine concentrations fell from 176 to 106 µmol/L after 1 h of haemoperfusion and the patient was rousable to voice and could obey commands at this time. She confirmed ingestion of 300 Tegretol‐CR® (200 mg) on extubation and was discharged without long‐term sequelae. Conclusion: Unrecognized poisoning with controlled‐release carbamazepine has the potential to produce significant delayed carbamazepine toxicity and delayed peak serum carbamazepine concentrations. This may occur much later than previously reported with immediate‐release carbamazepine preparations.

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Section: Discussionmentioning

confidence: 99%

Massive overdose with controlled‐release carbamazepine resulting in delayed peak serum concentrations and life‐threatening toxicity

2002

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“…CBZE DOI: 10.1159/000520520 is pharmacologically active and reaches a serum concentration of approximately 30% of CBZ [1]. Despite relatively high protein binding (75%) and moderate volume of distribution (0.8-1.4 L/kg), CBZ's low molecular weight (236 Da) allows for extracorporeal removal, particularly in a massive overdose, where serum protein binding is saturated and, in addition, protein binding for both CBZ and CBZE is concentration-dependent [2][3][4]. Thus, there are significantly higher amounts of free CBZ and CBZE in the serum during intoxication.…”

Section: Introductionmentioning

confidence: 99%

Combined Hemoperfusion and Continuous Veno-Venous Hemofiltration for Carbamazepine Intoxication

et al. 2021

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Introduction: Carbamazepine (CBZ) is a widely used anticonvulsant with a low molecular weight that allows for extracorporeal removal of free drug by both dialytic and hemoperfusion techniques, particularly in a massive overdose where serum protein binding is saturated. This report presents a case of CBZ intoxication where we were able to compare the mass removal of CBZ using hemoperfusion, with the mass removal of CBZ achieved with continuous renal replacement therapy (CRRT) during combined treatment. Methods: The Jafron HA230 resin hemoperfusion cartridge was applied in series with the continuous veno-venous hemofiltration (CVVH) circuit. Baseline and ongoing serum drug levels along with further samples from pre- and post-hemoperfusion cartridges and from CVVH effluent were collected. Results: Combined CVVH and resin hemoperfusion therapy in series was associated with a 50% reduction in the CBZ level from 16 mg/L to 8 mg/L over 3 h, far more rapid than that observed with CVVH alone or in the absence of extracorporeal drug clearance in the preceding hours. The combination therapy removed close to 35 mg/h of CBZ. Conclusion: The combination of CRRT and hemoperfusion can be easily deployed, appears safe, and is able to combine the CBZ mass removal achieved with each technique, thus to maximize CBZ extraction.

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“…A number of drugs such as quetiapine, phenytoin, and valproic acid have been reported to alter CBZ metabolism, significantly increasing serum levels of CBZE to as high as 90% to 150% of the parent drug [ 7 , 10 ]. An additional important feature of CBZE is that, unlike the parent drug CBZ, as serum CBZE levels rise protein binding is saturated and the amount of free CBZE increases, with subsequent increased availability for CNS toxicity [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Markedly Elevated Carbamazepine-10,11-epoxide/Carbamazepine Ratio in a Fatal Carbamazepine Ingestion

Russell

Spiller

Baker

2015

Case Reports in Medicine

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Carbamazepine is a widely used anticonvulsant. Its metabolite, carbamazepine-10,11-epoxide, has been found to display similar anticonvulsant and neurotoxic properties. While the ratio of parent to metabolite concentration varies significantly, at therapeutic doses the epoxide concentration is generally about 20% of the parent. We report a case of fatal carbamazepine overdose in which the epoxide metabolite concentration was found to be 450% higher than the parent compound, suggesting a potential role for metabolite quantification in severe toxicity.

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Carbamazepine and Carbamazepine-10,11-epoxide Pharmacokinetics in an Overdose Patient

Cited by 23 publications

References 13 publications

Massive overdose with controlled‐release carbamazepine resulting in delayed peak serum concentrations and life‐threatening toxicity

Massive overdose with controlled‐release carbamazepine resulting in delayed peak serum concentrations and life‐threatening toxicity

Combined Hemoperfusion and Continuous Veno-Venous Hemofiltration for Carbamazepine Intoxication

Markedly Elevated Carbamazepine-10,11-epoxide/Carbamazepine Ratio in a Fatal Carbamazepine Ingestion

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