Serum Carbamazepine Concentration Research Articles

Effects of major transporter and metabolizing enzyme gene polymorphisms on carbamazepine metabolism in Chinese patients with epilepsy.

The present study aimed to evaluate the effects of SNPs of major transporter and metabolizing enzyme genes on carbamazepine (CBZ) metabolism in Chinese patients with epilepsy. For 210 epileptic patients treated with CBZ as monotherapy, nine SNPs in candidate genes ABCB1, CYP3A4, CYP3A5, POR and EPHX1 were analyzed by PCR-RFLP or direct sequencing. Serum concentrations of CBZ, carbamazepine-10,11-epoxide (CBZE) and carbamazepine-10,11-trans dihydrodiol (CBZD) were determined by HPLC. Dose-adjusted concentrations of CBZ (CDRCBZ), CBZE (CDRCBZE), CBZD (CDRCBZ D) and CBZD:CBZE ratio were used as evaluation parameters for CBZ metabolism. The ABCB1 c.3435C>T was significantly associated with the CDR of CBZ and its major metabolites. CYP3A4*1G and CYP3A5*3 could influence CBZ metabolism, while POR*28 had no effect on it. The EPHX1 c.416A>G and c.128G>C variants were significantly associated with CBZD:CBZE ratio. Our data suggest that certain polymorphisms of major transporter and metabolizing enzyme genes could in part influence interindividual variability of CBZ metabolism in Chinese patients with epilepsy.

Association of ABCB1,CYP3A4,EPHX1,FAS,SCN1A,MICA, andBAG6 polymorphisms with the risk of carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in Chinese Han patients with epilepsy.

This study explored the association between the risk of carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and CBZ dose, dose-adjusted concentration, and ABCB1, CYP3A4, EPHX1, FAS, SCN1A, MICA, and BAG6 polymorphisms in patients of Han ethnicity with epilepsy who were living in northeastern China. We determined the genotypes of patients with CBZ-SJS/TEN and CBZ-tolerant patients, who were used as controls, for ABCB1, CYP3A4, EPHX1, FAS, SCN1A, MICA, and BAG6 polymorphisms by polymerase chain reaction (PCR) amplification and direct sequencing. We measured the steady-state serum CBZ concentrations using fluorescence polarization immunoassay for the control patients. We observed statistically significant differences in EPHX1 c.337T>C polymorphisms between patients with CBZ-SJS/TEN and CBZ-tolerant controls in terms of allelic and genotypic frequencies (p = 0.011 and p = 0.007, respectively). The C allele and the C-G diplotype of EPHX1 may play important roles in increasing the risk of CBZ-SJS/TEN development (odds ratio [OR] 0.478, 95% confidence interval [CI] = 0.267-0.855, p = 0.011; OR = 0.213, 95% CI = 0.049-0.930, p = 0.025, respectively). We did not observe any significant associations between ABCB1, CYP3A4, EPHX1, FAS, SCN1A, MICA or BAG6 genes and CBZ dose or dose-adjusted concentration in CBZ-tolerant patients. We found a significant association between EPHX1 c.337T>C polymorphisms and the development of CBZ-SJS/TEN in patients of Han ethnicity living in northeastern China. EPHX1 c.337T>C polymorphisms may contribute to the risk of severe CBZ-SJS/TEN by increasing the concentration of a CBZ metabolite, CBZ-10,11-epoxide, in patients with epilepsy.

Slow Carbamazepine Clearance in a Nonadherent Malay Woman With Epilepsy and Thyrotoxicosis

The authors describe a case of a 37-year-old Malay lady with an unusually slow carbamazepine clearance, which may be related to genetic polymorphisms of drug metabolizing enzymes and transporters. When given a small daily dose of 200 mg immediate-release carbamazepine, this patient experienced drowsiness. Subsequently, she reduced her carbamazepine dose to 200 mg twice a week (on Mondays and Fridays), resulting in poor seizure control. At the same time, the patient was diagnosed with hyperthyroidism and was given carbimazole and propranolol. Hyperthyroidism and the concurrent use of these antihyperthyroid agents may have further slowed down the metabolism of carbamazepine. Therapeutic drug monitoring of carbamazepine was carried out, and a slow carbamazepine clearance of 1.45 L·h⁻¹ per 70 kg was observed. Genotyping of selected genetic variants in CYP3A4, CYP3A5, EPHX1, ABCB1, and ABCC2 revealed that she has CYP3A5*3/*3 and ABCB1 3435-CC genotypes. Both genotypes have been shown to be associated with higher adjusted mean serum carbamazepine concentration in Chinese and Korean patients with epilepsy. Physicians should be vigilant about the risk of adverse effects among patients with a slow carbamazepine clearance, especially in Malays. Simulations of carbamazepine dosing regimen based on the pharmacokinetic parameters of this patient were performed to allow individualization of drug therapy.

Delayed Elevation in Carbamazepine Concentrations After Overdose

An initial carbamazepine concentration may initially be supratherapeutic, therapeutic, or even subtherapeutic only to persist to rise over time. The aim of this study was to report the frequency of toxic carbamazepine concentrations continuing to rise and to estimate how often an initially therapeutic or subtherapeutic concentration misrepresents the potential toxicity of an acute carbamazepine overdose. An 8-year retrospective search of all carbamazepine exposures reported to the Illinois Poison Center (January 1, 2001 through December 31, 2008) was reviewed. Inclusion criteria were acute poisonings with a documented carbamazepine concentration of >12 μg/mL at any time. Those with initial concentrations of >12 μg/mL that subsequently increased over time were recorded. Additionally, those cases that initially had therapeutic (4-12 μg/mL) or subtherapeutic (<4 μg/mL) concentration were identified. Descriptive statistics were used to analyze the data. A total of 1424 cases were reported. Of the 523 patients with documented concentrations of >12 μg/mL, 93 patients (17.8%) had initial carbamazepine concentrations >12 μg/mL and continued to rise. Sixteen patients (3.5%) had initial carbamazepine concentrations that were therapeutic (4-12 μg/mL) and 7 patients (1.3%) had initial carbamazepine concentrations <4 μg/mL before rising >12 μg/mL. Certain patients had progressive decreases in level of consciousness corresponding to increasing carbamazepine concentrations. Additionally, several patients with initial levels of therapeutic or subtherapeutic concentration later became comatose and required ventilator management. Initial serum carbamazepine concentrations can be misleading. Serial measurements documenting a declining carbamazepine concentration or prolonged observation are recommended when managing these overdoses.

Analysis of serum concentrations of anti-epilepsy drugs in 113 case-times

Objective To provide some references for clinical individualized mediaction analyzing the serum concentrations of anti-epilepsy drugs.Methods Enzyme-mutiplied immunoassay technique (EMIT)was used to determine the sermn concentrations of anti-epilepsy drugs in 113 case-times,then the concentrations were analyzed and compared with SPSS 16.0.The impact of age,sex,and drug combination on the serum concentrations of anti-epilepsy drugs and the relation between the serum concentrations of antiepilepsy drugs and therapeutic effect were analyzed.Results Among the serum concentrations of carbamazepine in 24 case-times,2 case-times whose diseases were totally controlled were lower than 4 μ g/ml;19 case-times between 4 and 12 μ g/ml,with an effective rate of 78.95％;3 case-times higher than 12 μ g/ml,with an effective rate of 66.67％.Among the serum concentrations of valproic acid in 74 case-times,24 case-times were lower than 50 μ g/ml,with an effective rate of 79.17％;43 case-times between 50 and 100 μ g/ml,with an effective rate of 81.40％;7 case-times higher than 100 μ g/ml,with an effective rate of 71.43％.Drug combination with carbamazepine had 13 case-times;61.54％ of the serum concentrations were within the effective range.Drug combination with valproic acid had 12 case-times;16.67％ of the serum concentrations were within the effective range.The impact of age,sex,and drug combination on the serum concentrations of anti-epilepsy drugs and the relation between serum concentration and therapeutic effect had no difference in statistics.Conclusions There are great individual differences among patients in the serum concentrations of antiepilepsy drugs.It is unilateral to adjust the dosage of drugs only depending on serum concentration.In clinical treatment,the serum concentrations of anti-epilepsy drugs are only references for adjusting drug dosage.We should adjust the drug dosage in term of the patients' conditions and the serum concentration of drug so that the patients will get the best therapeutic effect with a smallest drug dosage. Key words: Anti-epilepsy drugs; Serum concentration monitoring; Carbamazepine; Valproic acid

Effectivity of One Session Charcoal Hemoperfusion Treatment in Severe Carbamazepine Poisoning

A carbamazepine intoxication with suicide attempt is a relatively common clinical problem that presenting with coma, respiratory depression, arrhythmia, hemodynamic instability and even death. We report a case of severe carbamazepine poisoning that was successfully treated with one session charcoal hemoperfusion. On admission, the patient was comatose and required ventilator support. Hemoperfusion with coated activated charcoal successfully decreased the serum carbamazepine concentration from 45 µg mL−1 to 21 µg mL−1 within 2 h, with subsequent clinical improvement.

Analysis of carbamazepine serum by differential pulse voltammetry (DPV) and comparison with fluorescence polarization immunoassay (FPIA): an animal study

Few studies have investigated the value of using an electrochemical method with dropping mercury electrodes to determine carbamazepine level. However, the toxic mercury can result in environmental pollution. In our previous study, we successfully developed a differential pulse voltammetric (DPV) method using a glassy carbon electrode instead of a dropping mercury electrode for the determination of carbamazepine level in standard solutions. In this study, we used the DPV method to determine the serum level of carbamazepine in rabbits. Blood samples were obtained from rabbits which had been fed carbamazepine. The serum concentration of carbamazepine from DPV using glassy carbon electrode and fluorescence polarization immunoassay (FPIA) technique was compared using a correlation test. In addition, DPV and FPIA techniques in carbamazepine detection were evaluated for precision, linearity, and detection limits using a standard solution. The correlation between the carbamazepine concentrations from DPV compared with those by FPIA was good (RSQ = 0.998). In addition, the coefficient of variation (CV) for the DPV technique and the FPIA technique were low. The precision and detection limit for both methods were satisfactory. The DPV method using a glassy carbon electrode can be a potential method for the determination of carbamazepine in serum.

Toxicokinetics and correlation of carbamazepine salivary and serum concentrations in acute poisonings

Saliva is a body fluid which, like serum, can be used for determination of concentrations of certain drugs, both in pharmacotherapy as well as in acute poisonings. The aim of this study was to determine carbamazepine concentrations in both saliva and serum in acute poisoning in order to show if there is a correlation between the obtained values, as well as to monitor toxicokinetics of carbamazepine in body fluides. Saliva and serum samples were obtained from 26 patients treated with carbamazepine and 20 patients acutely poisoned by the drug immediately after their admission in the Emergency Toxicology Unit. Determination of salivary and serum carbamazepine concentrations was performed by the validated high pressure liquid chromatography-ultraviolet (HPLC-UV) method. A significant correlation of salivary and serum carbamazepine concentrations in both therapeutic application and acute poisoning (r = 0.9481 and 0.9117, respectively) was confirmed. In acute poisonings the mean ratio between salivary and serum concentrations of carbamazepine (0.43) was similar to the mean ratio after its administration in therapeutic doses (0.39), but there were high inter-individual variations in carbamazepine concentrations in the acutely poisoned patients, as a consequence of different ingested doses of the drug. In acute poisoning the halftime of carbamazepine in saliva and serum was 12.57 h and 6.76 h, respectively. Our results suggest a possible use of saliva as an alternative biological material for determination of carbamazepine concentrations in therapeutic application and acute poisoning as well, and a possible extrapolation of the results obtained in saliva to serum concentrations of carbamazepine.

カルバマゼピン類似体の交差反応を考慮したアーキテクト&lt;sup&gt;Ⓡ&lt;/sup&gt;･カルバマゼピンSTによる血中カルバマゼピン濃度測定に対する評価

カルバマゼピン類似体の交差反応を考慮したアーキテクト&lt;sup&gt;Ⓡ&lt;/sup&gt;･カルバマゼピンSTによる血中カルバマゼピン濃度測定に対する評価

Retrospective analysis of serum drug concentration monitoring in the Tenth People’s Hospital affiliated to Tongji University from 2003 to 2009

Objective:To summarize the results of serum drug concentration monitoring in the Tenth People's Hospital affiliated to Tongji University from 2003 to 2009.Methods:Serum concentrations of sodium valproate(255 cases),phenytoin sodium(33 cases),carbamazepine(48 cases) and digoxin(141 cases) were determined by immune fluorescence polarization method and the results were statistically analyzed.Results:Sodium valproate was the most frequently monitored drug among the three antiepileptic drugs,which accounted for 75.89%,while phenytoin sodium was the least.Serum concentration of carbamazepine of thirty-five cases was within the normal range,accounting for 72.92%(35/48),which was the highest among the three antiepileptic drugs.Serum concentration of digoxin of 114 cases was within the normal range,accounting for 80.85%(114/141).Conclusion:Serum drug concentration monitoring plays an important role in clinic.Its significance should be interpreted in conjunction with clinical manifestation.

Enantioselective Assay for Therapeutic Drug Monitoring of Eslicarbazepine Acetate: No Interference With Carbamazepine and Its Metabolites

As add-on therapy, phase III clinical trials of eslicarbazepine acetate (ESL) conducted in patients with refractory partial-onset seizures have shown good efficacy, safety, and tolerability, even in patients taking carbamazepine (CBZ) at baseline (approximately 60% of the enrolled patients). Thus, considering the pharmacological disadvantages of CBZ and the similar efficacy spectrum of CBZ and ESL, switching to ESL may be successful in many patients. As ESL is a prodrug almost instantaneously converted to S-licarbazepine (S-Lic; approximately 95%), an interest in therapeutic drug monitoring (TDM) of S-Lic is likely to develop in the future. This study investigated the plasma concentrations of S-Lic and R-licarbazepine (R-Lic) enantiomers in patients under CBZ long-term treatment to assess the potential interference of CBZ or its metabolites in the enantioselective TDM of ESL (using S-Lic concentrations). A chiral high-performance liquid chromatography assay with ultraviolet detection (HPLC-UV) previously developed and validated by our research group was used. Twenty-four patients admitted to the Coimbra University Hospital and supposedly receiving CBZ long-term treatment were identified. Blood samples were collected from patients and serum CBZ concentrations were measured by the usual TDM protocol. Aliquots of plasma from such patients were also submitted to a chiral HPLC-UV analysis. The bioanalytical data indicated that S-Lic and R-Lic were not present at detectable concentrations in plasma samples of the CBZ-treated patients. The chromatograms generated by the analysis of patient plasma samples, when compared with those obtained from blank plasma samples spiked with S-Lic and R-Lic, clearly showed the absence of interferences at the retention times of both Lic enantiomers. These data support the usefulness of the chiral HPLC-UV method used for the enantioselective TDM of ESL (using S-Lic) for programs in which switching from CBZ to ESL is implemented.

Comparison between the immunoassay and high performance liquid chromatography for therapeutic monitoring of carbamazepine and phenytoine

Objective: To investigate the correlation of the immunoassay and chromatography method for quantitative measurement of two antiepileptic drugs (AED), carbamazepine (CBZ) and phenytoin (PHT) and determination of relation between the CBZ and it’s metabolite carbamazepine 10,11epoxide (CBZ-E). Additionally we investigated whether there is a diff erence in the determination of serum concentration of CBZ and PHT when measured in two diff erent labs by high performance liquid chromatography (HPLC). Materials and methods: This study was carried out on 102 blood samples (72 CBZ and 30 PHT) collected from epileptic outpatients. Plasma concentrations of CBZ and PHT were determined by validated HPLC (Shimadzu and Agilent) and the CEDIA-immunoassay method. Results: The correlations of serum concentrations of CBZ between CEDIA and HPLC1 and between CEDIA and HPLC2 were good (R = 0.97 for both techniques). Even better correlation was found between concentrations of CBZ measured by the two HPLC systems (R = 0.99). Similar, for PHT, we found good correlation between CEDIA and the two systems of HPLC (HPLC1 and HPLC2, R = 0.98) and between the two systems of HPLC of R =0.98. The moderate correlation coeffi cient was found between serum concentrations of CBZ and its metabolite CBZ-E, measured in two labs by diff erent HPLC (R = 0.49 and 0.43, respectively; P < 0.001). Conclusion: We observed good correlation for estimation of CBZ and PHT concentration obtained by means the immunoassay and two diff erent HPLC. The possibility of measurement of CBZ-E could be advantage of chromatography in comparison with immunoassay.

Carbamazepine-induced hyperammonemia

A case of carbamazepine-induced hyperammonemia is presented. A 26-year-old man with bipolar disorder, seizures, and mild mental retardation secondary to a traumatic brain injury began treatment with carbamazepine for aggression and seizure control. After three weeks of carbamazepine therapy, the patient arrived at the emergency department (ED) with severe agitation and aggressive behavior. His oral medications included topiramate, carbamazepine, olanzapine, quetiapine, guanfacine, and desmopressin acetate. The patient's medications had been stable for at least six months except for the addition of carbamazepine one month before his arrival at the ED. Upon admission, the patient's vital signs were found to be within normal limits, as were his liver profile results, complete blood count, thyroid-stimulating-hormone level, and serum chemistry panel. His serum carbamazepine concentration was 3.9 microg/mL (reference range, 4-12 microg/mL), and his serum ammonia concentration was 127 microg/dL (reference range, 19-60 microg/dL). Carbamazepine was discontinued upon admission, and the patient was treated with oral lactulose. Since carbamazepine was discontinued and had been prescribed for bipolar disorder, his olanzapine dosage was increased, and trazodone was added at bedtime for insomnia. Of note, the patient had been on carbamazepine therapy one year earlier and had experienced the same adverse event. He had also developed elevated serum ammonia levels while on valproic acid. The patient's serum ammonia level returned to normal by hospital day 4, and he was discharged to his group home. A 26-year-old man with bipolar disorder developed hyperammonemia three weeks after initiating carbamazepine therapy.

Effect ofCYP3A5*3genotype on serum carbamazepine concentrations at steady-state in Korean epileptic patients

Carbamazepine (CBZ) is metabolized mainly by the CYP3A family of enzymes, which includes CYP3A4 and CYP3A5. Several studies have suggested that the CYP3A5*3 genotype influences the pharmacokinetics of CYP3A substrates. The present study aimed to assess the effect of the CYP3A5*3 genotype on serum concentration of CBZ at the steady-state in Korean epileptic patients. The serum concentrations of CBZ in 35 Korean epileptic patients were measured and their CYP3A5 genotype was determined. Fourteen patients were CYP3A5 expressors (two for CYP3A5*1/*1 and 12 for CYP3A5*1/*3) and 21 patients were CYP3A5 non-expressors (CYP3A5*3/*3). Dose-normalized concentrations (mean +/- SD) of CBZ were 9.9 +/- 3.4 ng/mL/mg for CYP3A5 expressors and 13.1 +/- 4.5 ng/mL/mg for CYP3A5 non-expressors (P = 0.032). The oral clearance of CBZ was significantly higher in CYP3A5 non-expressors than that of CYP3A5 expressors (0.056 +/-0.017 L/h/kg vs. 0.040 +/- 0.014 L/h/kg, P = 0.004). The CYP3A5 genotype affected the CBZ concentrations in Korean epileptic patients and is a factor that may contribute to inter-individual variability in CBZ disposition in epileptic patients.

Value of saliva samples in monitoring carbamazepine concentrations in epileptic patients.

Simultaneous saliva and serum concentrations of carbamazepine (CBZ) were determined by enzyme immunoassay technique (EMIT) in 120 epileptic patients on long-term treatment with CBZ. Saliva specimens were collected after the patients had chewed paraffin for 5 min. The regression between serum and saliva concentrations of CBZ was linear. The correlation coefficient was 0.94 with a mean saliva/serum ratio of 0.31 (0.30-0.31, 95% confidence limits). The serum/saliva correlation coefficients r = 0.92 and r = 0.95, as well as the mean saliva/serum ratios, 0.31 and 0.31, were comparable in 83 patients in CBZ monotherapy and 37 patients receiving additional drugs. The paraffin chewing facilitated the saliva sampling greatly, but resulted only in a minor increase of the serum/saliva correlation coefficient, 0.90 to 0.94, based on 45 patients on CBZ monotherapy where saliva was sampled just before as well as after paraffin chewing. The method of saliva sampling failed in five patients (4%), but was otherwise applicable even in little children. The findings indicate that the concentrations of CBZ in saliva instead of serum can be used to monitor CBZ treatment in epileptic patients, thus obviating the necessity of painful venipunctures.

Influence of disulfiram on the serum concentration of carbamazepine in patients with epilepsy

Treatment of alcoholics with phenytoin and disulfiram (DI) simultaneously is complicated and inexpedient because of the marked drug interaction. The aim of this study was to investigate whether an interaction exists between DI and carbamazepine (CBZ). The serum levels of CBZ and the metabolite CBZ-10, 11-epoxide were measured by high-pressure liquid chromatography in seven out-patients with epilepsy, on monotherapy with CBZ, before and during two weeks administration of DI. Five patients completed the investigation. None were alcoholics. The changes in the serum levels were insignificant, i.e. without clinical important. Moreover, uncontrolled clinical experience has not indicated any interaction between DI and CBZ. Thus the influence of DI on the metabolism of CBZ is probably negligible. CBZ is suggested, therefore, when anticonvulsive therapy is needed by alcoholics in treatment with DI.

A controlled study with taltrimide and sodium valproate: valproate effective in partial epilepsy

Taltrimide was compared with valproate and placebo in 17 patients with intractable epilepsy being on carbamazepine monotherapy. Taltrimide (400 mg/day), valproate (1000 mg/day) or placebo were added to the treatment for periods of 3 months using a randomized cross-over design. Serum carbamazepine concentrations remained within the therapeutic range throughout the trial. Thirteen patients completed the study. In partial epilepsy of 7 the seizure frequency was reduced by 27% during valproate (p less than 0.05), compared with placebo, while no improvement was found during taltrimide. In 6 with primary generalized epilepsy, the number of seizures was reduced by 49% during taltrimide and by 38% during valproate, but neither effect was significant, compared with placebo. Headache was reported by 3 patients while on taltrimide. One with hypersensitivity history developed petecchiae and nasal bleeding during taltrimide and, therefore, the treatment was stopped. The three other interruptions were independent of taltrimide. Thus, the only statistically significant effect in this study was that of valproate in partial epilepsy.

Can Epileptic Patients on Carbamazepine Safely Fast Ramadan?

DOI: http://dx.doi.org/10.5915/40-4-4433 Objective : To study the effect of fasting during Ramadan on the epileptic state of well-controlled epileptic patients taking the same protective doses of carbamazepine (CBZ) as they did before Ramadan. Study design : A case series study including 40 epileptic patients in Mosul, Ninevah Province, Iraq, before Ramadan 1420 AH, which began December 9, 1999 CE. The patients were taking carbamazepine three times daily, and their epilepsy was well controlled. During Ramadan fasting, the same total daily amount of carbamazepine was administered, twice daily rather than three times daily. A blood sample was taken from each patient 10 days before fasting Ramadan and two samples on the 15th day of Ramadan, one at 9 a.m. (4 hours after the morning dose) and the second at 4 p.m. (1 hour prior to second dose). Serum CBZ concentration was measured by gas liquid chromatography, glucose was measured by glucose oxidase method, and sodium and potassium were measured by flame emission photometry. Results : Statistical comparison between the means of CBZ concentration before Ramadan (control) and those of sample 1 (p> 0.1) and sample 2 (p> 0.5) during fasting in Ramadan showed no significant statistical differences. Also, there were no significant statistical differences between samples 1 and 2 during Ramadan (p> 0.1). The values of glucose, sodium, and potassium remained within their normal ranges during Ramadan. Conclusion : The present study showed that epileptic patients taking continuous prophylactic doses of CBZ two times daily can safely fast Ramadan safely.

Carbamazepine dose–concentration relationship in elderly nursing home residents

To describe the dose-concentration relationships of carbamazepine (CBZ) in elderly nursing home residents and the effect of sex, age, and type of co-medications. This is a cross-sectional study of elderly (> or = 65 years) nursing home residents across the United States (N=92). Data collection was from 1 June 1998 to 31 December 2000. The mean CBZ dose was 9.2+/-5.4 mg/(kg day(-1)) (+/-Standard Deviation) and serum concentration was 5.9+/-2.2mg/L. The daily dose was significantly lower in the oldest-old age group (> or = 85 years, mean 476.9 mg/day (95% confidence interval CI) 326.5-627.3) as compared to the dose in the young-old (65-74 years, mean 724.4 mg/day (CI) 603.4-845.4) (p=0.016). Adjusted for body weight, doses were similar on a mg/(kg day(-1)) basis. The majority of observed CBZ serum concentrations were at the lower end (67.4%) or below (20.7%) the suggested therapeutic range for younger adult outpatients. Total daily CBZ doses and patient weight decreased with age. The average dose for elderly nursing home residents was approximately 9 mg/(kg day(-1)). Carbamazepine serum concentrations were lower than those used for younger adults, suggesting that these patients may be more sensitive to CBZ.

Limited Efficacy of Gastrointestinal Decontamination in Severe Slow-Release Carbamazepine Overdose

To report the limited efficacy of both multiple doses of activated charcoal (MDAC) and whole bowel irrigation (WBI) in a patient with severe overdose of slow-release carbamazepine. A 25-year-old man was admitted in a comatose state with seizures after a suicide attempt with slow-release carbamazepine. Serum carbamazepine concentration on admission (16 h postingestion) was 52.08 microg/mL. The patient was mechanically ventilated and treated with MDAC and a 4 hour charcoal hemoperfusion. Carbamazepine concentration at the end of hemoperfusion was 27.16 microg/mL. Despite continuous treatment with MDAC, a rebound in carbamazepine concentration to 36 microg/mL was observed 32 hours after hemoperfusion (58 h postingestion). WBI was performed over a 10 hour period. The carbamazepine concentration continued to increase to 38.55 microg/mL and seizures recurred. After WBI was performed, MDAC was reinstituted; 33 hours later (102 h postingestion), the carbamazepine concentration began to decline. The hospitalization course was complicated by pneumonia, which necessitated continuation of mechanical ventilation and administration of antibiotics. The patient recovered completely and was discharged without sequelae 15 days after admission. Serum carbamazepine concentration and toxicity were effectively reduced by hemoperfusion. The role of MDAC coadministered during hemoperfusion cannot be ruled out. However, a rebound in carbamazepine concentration with recurrent seizures was observed despite MDAC and WBI. The most likely explanation for this rebound (65 h postingestion, 39 h posthemoperfusion) is prolonged absorption, possibly from a pharmacobezoar. Redistribution cannot be excluded, but this is not supported by the concentration-time course and previous reports. Both MDAC and WBI may be ineffective in reducing absorption and enhancing elimination in overdose of slow-release carbamazepine. Repeated hemoperfusion or other elimination enhancement techniques should be considered when the clinical and toxicokinetic course suggests the presence of a refractory pharmacobezoar.