Changes in the disposition of oxcarbazepine and its metabolites during pregnancy and the puerperium

PURPOSE: To determine potential changes in the plasma concentrations of oxcarbazepine (OXC) and its metabolites during pregnancy and puerperium. METHODS: Five women receiving OXC monotherapy were followed prospectively during pregnancy and the puerperium. Four women were enrolled in the first trimester, and one woman, 2 weeks before delivery. Steady-state concentrations of OXC, its active R-(-)- and S-(+)-monohydroxy derivatives (MHD), and the additional metabolite carbamazepine-10,11-trans-dihydrodiol (DHD) were measured at regular intervals by an enantioselective HPLC assay. RESULTS. In all samples, S-(+)-MHD was the most abundant compound in plasma and accounted almost entirely for the amount of active moiety (defined as the molar sum of OXC, R-(-)-MHD, and S-(+)-MHD) found in the circulation. The dose-normalized concentrations of active moiety decreased markedly during gestation and, in four of the five patients, increased strikingly after delivery. Plasma concentrations of S-(+)-MHD mirrored closely the levels of the active moiety. Plasma concentrations of the parent drug and other metabolites also tended to decrease during pregnancy and to increase after delivery. CONCLUSIONS: During treatment with OXC, S-(+)-MHD is by far the most abundant active compound in plasma. The concentration of this metabolite as well as the active moiety may decrease markedly during pregnancy and may increase severalfold after delivery. Because of these striking pharmacokinetic changes, the clinical response should be monitored closely in OXC-treated women throughout pregnancy and the puerperium.     

Drug monitoring of lamotrigine and oxcarbazepine combination during pregnancy

Little is known about pregnancy-induced alterations in the pharmacokinetics of the newer antiepileptic drugs, especially when used in combinations. Two women receiving combination therapy of lamotrigine (LTG) and oxcarbazepine (OXC) were followed prospectively during pregnancy and puerperium. Steady-state concentrations of LTG and the active metabolite of OXC, 10-hydroxycarbazepine (MHD), were measured at regular intervals using a dried blood spot method, and clearances were calculated. A strong effect of pregnancy on the clearance of both LTG and MHD was seen. An increase in seizure frequency occurred in both women. This stresses the importance of therapeutic drug monitoring of LTG and MHD during pregnancy. In case of breakthrough seizures or increased seizure frequency, dosage adjustment of both drugs may be required.     

Efficacy, tolerability, and pharmacokinetics of oxcarbazepine oral loading in patients with epilepsy

The rapid achievement of effective levels of antiepileptic drugs (AEDs) is required in patients with epilepsy who have a higher risk of seizures, and oral loading of AEDs may be an important consideration in these patients. We performed the present study to investigate the efficacy and tolerability of oral loading of oxcarbazepine in patients with recurrent seizures, or after temporary discontinuation of AEDs for diagnostic or presurgical evaluation of epilepsy. Forty adult patients were studied and oxcarbazepine was administered orally at a single loading dosage of 30 mg/kg. The plasma levels of oxcarbazepine and its active metabolite, 10,11-dihydro-10-hydroxy-carbazepine (monohydroxy derivative, MHD), were measured, and clinical assessment of adverse events was performed at 2, 4, 6, 8, 10, 12, 16, and 24 h after oral loading of oxcarbazepine. Approximately two-thirds of patients reached effective levels of MHD 2 h after receiving the oral loading, and all patients reached effective levels 4 h after oxcarbazepine administration. Most patients maintained therapeutic MHD levels for at least 16 h. Almost half of the patients experienced adverse events, but all were mild to moderate in severity and resolved spontaneously within 24 h. Our study shows that oral loading of oxcarbazepine is an effective and well-tolerated method for rapidly achieving therapeutic levels of MHD in patients with epilepsy, and is a useful option in selected patients with recurrent seizures, or after temporary discontinuation of AEDs.     

Hyponatremia induced by oxcarbazepine in children

We report the case of a 12-year-old girl with severe clinically relevant hyponatremia (118 mmol/l) and hypochloremia (81 mmol/l) during treatment with oxcarbazepine (OCBZ). The adverse effects were rapidly reversible after discontinuation of OCBZ and did not occur when exposed to carbamazepine. We reviewed the charts of 48 patients who received OCBZ as in-patients in our epilepsy centre and found hyponatremia in nine and hypochloremia in four. The mean sodium level of all patients was 139 mmol/l (range 118–150 mmol/l). We did not see any correlation between sodium or chloride levels and dose of OCBZ or blood serum level of the active metabolite 10-OH-carbazepine. We emphasize that children are at risk of developing electrolyte disturbances during treatment with OCBZ and thus the level of at least sodium should be monitored in those patients.     

Steady‐state plasma and cerebrospinal fluid pharmacokinetics and tolerability of eslicarbazepine acetate and oxcarbazepine in healthy volunteers

Purpose: To evaluate the pharmacokinetics and tolerability of once‐daily eslicarbazepine acetate (ESL) and twice‐daily oxcarbazepine (OXC) and their metabolites in cerebrospinal fluid (CSF) and plasma following repeated oral administration. Methods: Single‐center, open‐label, randomized, parallel‐group study in healthy volunteers. Volunteers in ESL group (n = 7) received 600 mg on days 1–3 and 1,200 mg on days 4–9, once daily. Volunteers in the OXC group (n = 7) received 300 mg on days 1–3 and 600 mg on days 4–9, twice daily. Plasma and CSF sampling was performed following the last dose. Key Findings: Eslicarbazepine was the major drug entity in plasma and CSF, accounting for, respectively, 93.84% and 91.96% of total exposure in the ESL group and 78.06% and 76.42% in the OXC group. The extent of exposure to drug entities R‐licarbazepine and oxcarbazepine was approximately four‐fold higher with OXC as compared with ESL. There was relatively little fluctuation from peak‐to‐trough (ratio) in the CSF for both eslicarbazepine (ESL = 1.5; OXC = 1.2) and R‐licarbazepine (ESL = 1.2; OXC = 1.2). In contrast, oxcarbazepine showed larger differences between peak and trough (ESL = 3.1; OXC = 6.4). A total of 84 and 24 treatment‐emergent adverse events (TEAEs) were reported with OXC and ESL, respectively. Significance: In comparison to OXC, administration of ESL resulted in more eslicarbazepine, less R‐licarbazepine, and less oxcarbazepine in plasma and CSF, which may correlate with the tolerability profile reported with ESL. The smaller peak‐to‐trough fluctuation of eslicarbazepine in CSF (a measure of sustained delivery to the brain) than in plasma supports once‐daily dosing of ESL.     

奥卡西平治疗儿童部分性发作的临床疗效及安全性观察

目的观察及评价奥卡西平（OXC）对儿童部分性发作的临床疗效和安全性。方法2006年3月-2007年5月经门诊诊断的PS／CPS或sGTCS儿童患者81例，其中27例采用奥卡西平添加治疗，54例单药治疗，经4～6周加量期和12周稳定期观察后进行评价。结果OXC添加治疗组及单药治疗组总有效率分别为81．5％和83．3％，完全控制率分别为37．0％和40．7％，且不良反应较轻，耐受性良好。结论奥卡西平治疗儿童部分性发作有效且安全，可用于儿童部分性发作的单药治疗和添加治疗。     

Vitamin D levels and bone turnover in epilepsy patients taking carbamazepine or oxcarbazepine

PURPOSE: Evidence suggests that enzyme-inducing antiepileptic drugs (AEDs) may decrease serum 25-hydroxyvitamin D (25-OHD) levels and increase bone turnover. We sought to determine whether these are affected by treatment with carbamazepine (CBZ) or oxcarbazepine (OXC). METHODS: We measured serum levels of 25-OHD, parathyroid hormone (PTH), osteocalcin (OCLN), bone alkaline phosphatase (BAP), and urinary N-telopeptides of type I collagen cross-links (NTX) in normal controls (n=24) and in epilepsy patients taking CBZ (n=21) or OXC (n=24) in monotherapy. CBZ patients were subsequently switched overnight to OXC monotherapy, and after 6 weeks, the tests were repeated. RESULTS: 25-OHD levels were lower in each drug-treated group (OXC, 19.4+/-2.3 pg/ml; CBZ, 20.4+/-2.4) than in the controls (27.5+/-2.8) (ANOVA, p=0.052). This difference was significant for the OXC group (p<0.05). PTH, BAP, and NTX did not differ significantly among groups. OCLN levels were somewhat elevated in the OXC group (2.79+/-0.47 ng/ml) and more clearly and significantly elevated in the CBZ group (3.63+/-0.36) compared with controls (2.38+/- 0.41) (p=0.053). Because the data were very similar between OXC and CBZ groups, they were combined to increase statistical power. The combined drug-treatment group had significantly higher BAP (p=0.02) and lower 25-OHD (p=0.015) than did controls. The latter remained significant even after accounting for the confounding effects of age on 25-OHD levels (p<0.05). No significant differences were found after CBZ patients were switched to OXC. CONCLUSIONS: Epilepsy patients taking OXC or CBZ have significantly lower 25-OHD than do normal controls, with a pattern of changes in other bone biomarkers suggestive of secondary hyperparathyroidism. It may be prudent for patients taking CBZ or OXC to be prescribed 25-OHD replacement.     

奥卡西平治疗癫癎的临床研究

目的观察奥卡西平(OXC)治疗癫癎的疗效、耐受性和安全性。方法294例患者,120例加用OXC治疗,174例单用OXC治疗。通过逐步加量的方法达到目标剂量。结果本组总有效率为86.05%,完全控制为39.8%;其中单药治疗组控制率45.98%,总有效率为89.08%,添加治疗组控制率为30.83%,总有效率为81.67%。单药治疗组不良反应总发生率为15.52%,添加组不良反应发生率为26.67%,2组比较,添加治疗组出现的反应相对多于单药治疗组。结论奥卡西平治疗癫癎有效、安全、稳定。     

Plasma concentrations of risperidone and olanzapine during coadministration with oxcarbazepine

PURPOSE: Oxcarbazepine (OZC) is a second-generation antiepileptic drug (AED) that also may be used as a mood stabilizer. Unlike carbamazepine (CBZ), which is an inducer of the cytochrome P-450 isoforms and may accelerate the elimination of several therapeutic agents, OXC seems to have only a modest inducing action. The aim of this investigation was to evaluate the effect of a treatment with OXC on plasma concentrations of the new antipsychotics risperidone and olanzapine. METHODS: OXC, at a dosage of 900-1,200 mg/day, was administered for 5 consecutive weeks to 25 outpatients, 10 men and 15 women, aged 25 to 64 years, with bipolar or schizoaffective disorder. Twelve patients were stabilized on risperidone therapy (2-6 mg/day) and 13 on olanzapine (5-20 mg/day). Steady-state plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) and olanzapine were measured by high-pressure liquid chromatography (HPLC) before addition of OXC and after 5 weeks from the start of adjunctive treatment. RESULTS: OXC caused only minimal and no significant changes in the mean plasma levels of risperidone (from 5.6 +/- 3.6 ng/ml at baseline to 4.8 +/- 2.6 ng/ml at week 5), 9-OH-risperidone (from 23.6 +/- 7.5 to 24.7 +/- 7.4 ng/ml), and olanzapine (from 26.5 +/- 5.7 ng/ml at baseline to 27.8 +/- 5.1 ng/ml). OXC coadministration with either risperidone or olanzapine was well tolerated. CONCLUSIONS: Our findings indicate that OXC does not affect the elimination of risperidone and olanzapine, thus confirming its weak inducing effect on hepatic drug-metabolizing enzymes.     

拉莫三嗪与奥卡西平单药治疗成人新诊断局灶性癫痫的长期疗效及安全性比较

目的 比较拉莫三嗪(LTG)和奥卡西平(OXC)单药治疗成人新诊断局灶性癫痫的长期疗效、耐受性和安全性。方法 收集本院癫痫专病门诊新诊断的局灶性癫痫,随机分成OXC组和LTG组,根据临床情况调整剂量,OXC最大剂量1200 mg/d,LTG最大剂量300 mg/d,至少随访3年,评估二种药物单药治疗成人新诊断局灶性癫痫无发作率、保留率及不良反应。结果 2009年6月-2016年6月符合入组标准146例,其中OXC组74例,LTG组72例,2组1年无发作率分别为35.1%和51.3%(χ2=3.9,P=0.047),3年无发作率分别为21.6%和40.2%(χ2=5.96,P=0.015),LTG组总体无发作率高于OXC组(P<0.05); OXC组和LTG组1年保留率分别为59.5%和69.4%(χ2=1.59,P=0.208),3年保留率分别为44.6%和51.4%(χ2=0.68,P=0.411),LTG组总体保留率亦高于OXC组,但无明显差异(P>0.05)。OXC组和LTG组最常见的不良反应均为皮疹(6.8% vs. 8.3%)。结论 LTG单药治疗新诊断成人局灶性癫痫的长期无发作率高于OXC,两者不良反应较轻,有较好的安全性。     

Effects of oxcarbazepine and phenytoin on the EEG and cognition in healthy volunteers

We studied the EEG and cognitive effects of oxcarbazepine (OXC) and phenytoin (PHT) using a double-blind, randomized, parallel-group design. Thirty-two healthy volunteers received a maximum of 1200 mg of OXC or 360 mg of PHT. EEG and cognitive testing were performed at baseline and after 12 weeks of treatment. For each subject and measure, test-retest Z scores were calculated from regression equations derived from 73 healthy controls. Twenty-six subjects completed the study. Both the OXC and PHT groups had significant slowing of the EEG peak frequency and increased relative theta and delta power. Differences between AEDs (antiepileptic drugs) were not significant. Significant cognitive effects were seen on 5 of 20 measures, primarily measures of motor speed and reaction time. Again, there were no significant differences between AEDs. The only significant difference between AEDs was for the POMS-Vigor scale, favoring OXC. The small sample size may have contributed to the lack of significant differences between AEDs.     

奥卡西平辅助治疗精神分裂症及分裂样精神病兴奋躁动的比较研究

目的评估奥卡西平治疗兴奋躁动精神分裂症、分裂样精神病辅助疗效和安全性。方法将符合中国精神障碍分类与诊断标准第3版中精神分裂症、分裂样精神病诊断标准,并以兴奋躁动为主要表现的80例患者随机分为研究组(n=39)和对照组(n=41),研究组应用抗精神病药物(氯氮平、奥氮平、利培酮、喹硫平、阿立哌唑或齐拉西酮其中之一)联合奥卡西平,对照组单一使用抗精神病药物,观察6周。采用简明精神病量表(BPRS)和阳性和阴性综合征量表(PANSS)兴奋因子,不良反应量表(TESS)在治疗前及治疗后第1,2,4,6周分别评估疗效和安全性。结果治疗6周后,研究组有效28例(71.8%),对照组有效26例(65.0%),2组有效率差异有统计学意义(χ2=6.02,P=0.028)。研究组与对照组患者分别脱落2例和4例。研究组的主要不良反应为镇静(11例)、便秘(10例)、头晕(7例)、心动过速(7例)等,对照组的主要不良反应为便秘(14例)、口干(12例)、心动过速(12例)、锥体外系不良反应(7例)等。结论奥卡西平能有效辅助治疗精神分裂症、分裂样精神病的兴奋状态。     

Effects of chronic treatment with valproate and oxcarbazepine on ovarian folliculogenesis in rats

Purpose : We aimed to define the morphologic effects of valproate (VPA) and oxcarbazepine (OXC) on ovarian folliculogenesis in rats.
Methods : Forty female wistar rats (21–24 days old and weighted between 46.4 and 55.3 g) were divided equally into 4 experimental groups, which were applied tap water (control group), 300 mg/kg/day VPA, 100 mg/kg/day OXC, and both VPA and OXC via gavage for 90 days. Ovaries of the rats on proestrous and diesterous phase of estrous cycle according to daily vaginal smear were taken out and placed in a fixation solution. Immunohistochemical and apoptosis (TUNEL) staining protocols were applied.
Results : The number of follicles decreased and that of corpora lutea increased significantly in OXC, VPA, and OXC+VPA treated groups compared with control group (p < 0.05). The number of TUNEL positive ovarian follicles was 1.40 ± 0.52 in control group, but it significantly increased to 3.50 ± 0.53, 3.50 ± 0.53, and 4.90 ± 0.88 in VPA, OXC, and VPA+OXC groups (p < 0.0001). The increase in the number of TUNEL positive granulosa cells was also significant for OXC and VPA+OXC groups (p < 0.0001). Immunohistochemical HSCORE decreased for TGFβ1 and IGF1 staining and increased for P53 staining in all drug groups compared with control group (p < 0.001). Intensity of P53 labeling increased, while intensity of TGFβ1, IGF-1, and GDF-9 immunoreactivity decreased significantly in all drug groups compared with control group (p < 0.001).
Conclusion : Long-term treatment with VPA or OXC from prepuberty to adulthood causes apoptosis and deterioration of folliculogenesis in rat ovarian follicles.     

Effects of carbamazepine and oxcarbazepine on the reproductive endocrine function in women with epilepsy

PURPOSE: The aim of the study was to compare the effects of carbamazepine (CBZ) and oxcarbazepine (OXC) on the reproductive endocrine function in women with epilepsy. OXC is a novel antiepileptic drug (AED), and the occurrence of reproductive dysfunction in women treated with OXC monotherapy for epilepsy has not been studied previously. METHODS: Thirty-five women with epilepsy were examined in the Department of Neurology at Oulu University Hospital. Sixteen patients were treated with CBZ monotherapy, and nineteen patients were treated with OXC monotherapy. The subjects were clinically examined, vaginal ultrasonography was performed, and serum sex hormone concentrations were measured. RESULTS: The women taking CBZ or OXC had lower serum testosterone (T) levels and lower free androgen indexes (FAIs) than the control subjects. CBZ medication was associated with increased concentrations of serum sex hormone-binding globulin (SHBG). The patients taking OXC had higher concentrations of dehydroepiandrosterone sulfate (DHEAS) and androstendione (A) than did the women taking CBZ. Moreover, the prevalence of polycystic ovaries (PCOs) was high in the OXC-treated women. CONCLUSIONS: CBZ and OXC have different effects on the reproductive endocrine function. Although both drugs were associated with low serum T concentrations and low FAIs, only OXC was associated with a high frequency of elevated levels of A and DHEAS and with an increased prevalence of PCOs. These findings suggest that OXC may be disadvantageous for women with epilepsy and hyperandrogenism, whereas CBZ may be beneficial for these women.     

Worsening of seizures by oxcarbazepine in juvenile idiopathic generalized epilepsies

PURPOSE: Several studies have shown that carbamazepine (CBZ) may aggravate idiopathic generalized epilepsy (IGE). Oxcarbazepine (OXC) is a new drug chemically related to CBZ. We report six cases of juvenile IGE with a clear aggravation by OXC. METHODS: We retrospectively studied all patients with IGE first referred to our epilepsy department between January 2001 and June 2003 and treated with OXC. RESULTS: During this period, six patients were identified. All had an aggravation of their epilepsy in both clinical and EEG activities. OXC had been used because of an incorrect diagnosis of focal epilepsy or generalized tonic-clonic seizures (GTCSs) of undetermined origin (no syndromic classification of the epilepsy). Before OXC, only one patient had experienced a worsening of seizures with an inadequate drug (CBZ). Four had juvenile myoclonic epilepsy, one had juvenile absence epilepsy, and one had IGE that could not be classified into a precise syndrome. OXC (dosage range, 300-1,200 mg/day) was used in monotherapy in all of them except for one patient. Aggravation consisted of a clear aggravation of myoclonic jerks (five cases) or de novo myoclonic jerks (one case). Three patients had exacerbation of absence seizures. One patient had worsened dramatically and had absence status, and one had de novo absences after OXC treatment. The effects of OXC on GTCSs were less dramatic, with no worsening in frequency in three and a slight increase in three. CONCLUSIONS: OXC can be added to the list of antiepileptic drugs that can exacerbate myoclonic and absence seizures in IGE.     

Histologic and morphologic effects of valproic acid and oxcarbazepine on rat uterine and ovarian cells

Purpose:   To determine the histologic and morphologic effects of valproic acid (VPA) and oxcarbazepine (OXC) on rat uterine and ovarian cells.
Methods:   Fifty-six female prepubertal Wistar rats (21–24 days old and weighing between 47.5 and 58.1 g) were divided equally into four groups, which were given drinking water (controls), 300 mg/kg/day of VPA, 100 mg/kg/day of OXC or VPA + OXC via gavage, for 90 days. Ovaries and uteri of rats on proestrous and diestrous phases of estrous cycle were extirpated and placed in a fixation solution. The tissue specimens were assessed with apoptosis (TUNEL) staining protocols, eosinophil counting, and electron microscopic techniques.
Results:   In uteri, apoptosis in stroma, mitochondrial swelling, and cristolysis were observed in the VPA group, and OXC led to negative effects on epithelial cell and intracellular edema. In ovaries, both drugs increased apoptosis and intracytoplasmic edema. Organelle structure disruption was also observed in the OXC group. More conspicuous degenerative modifications were determined in the VPA + OXC group. In uteri, the number of TUNEL-positive luminal epithelial cells was 7.20 ± 1.32 in controls, and significantly increased to 29.60 ± 1.58, 34.20 ± 2.53, and 54.80 ± 2.04 in VPA, OXC, and VPA + OXC groups, respectively (p < 0.001). The highest number of TUNEL-positive glandular epithelium cells was observed in the VPA + OXC group; however, the number of TUNEL-positive stroma cells was highest in the VPA group. The highest number of eosinophils in stroma was in the VPA group.
Conclusion:   VPA and OXC trigger apoptotic and degenerative effects on rat uterine and ovarian cells. VPA also prevents implantation of embryo to the uterus and causes abortion via endometrial eosinophil infiltration.     

Aggravation of seizures and/or EEG features in children treated with oxcarbazepine monotherapy

PURPOSE: Exacerbation of epilepsy may occur following initiation of therapy with antiepileptic drugs (AEDs). The aim of this study is to analyze the clinical and EEG characteristics of a group of pediatric patients with worsening of seizures and/or EEG deterioration while on oxcarbazepine (OXC). METHODS: A retrospective analysis of a clinical database was performed to identify patients with epilepsy treated with OXC over the past 3 years. History, neurological examination, and EEG findings were reviewed to identify any who had developed exacerbation of seizures or new abnormalities on EEG. RESULTS: Of 290 patients on OXC, we identified 12 patients with new onset seizures, all with initial normal neurological exam and normal EEG, who developed either worsening of preexisting seizures, new seizure types, and/or EEG deterioration following introduction of OXC monotherapy. EEG changes were primarily characterized by new onset of generalized epileptiform activity not reported on the initial baseline EEG. Following substitution of OXC with a broad spectrum AED, significant improvement of seizure control and improvement in the EEG was observed. CONCLUSIONS: These findings suggest that OXC can aggravate seizures and/or worsen EEG features in children. Following initiation of therapy with OXC, monitoring of patients with follow-up EEGs may be important, especially in patients who do not show adequate response to therapy.     

奥卡西平单药治疗和辅加治疗对国人癫癎疗效和副反应的对照研究

目的评价奥卡西平（OXC）作为辅加药物治疗癫癎（Ⅰ组）以及单药治疗新诊断癫癎患者（Ⅱ组）在疗效、毒副作用方面的差异。方法Ⅰ组101例以OXC作为辅助添加剂治疗（OXC150～1200mg／d，中位数600rag／d），Ⅱ组23例以OXC作为单药治疗（OXC150～600mg／d，中位数450mg／d），随访3～25月；对2组患者治疗前后的发作频率、初始目标剂量、退出治疗情况、毒副作用进行对照分析或描述比较。结果Ⅰ、Ⅱ组发作控制率有非常显著性差异（P〈0．01），两组总有效率无显著性差异（P〉0．05）；2组的初始目标剂量无显著性差异（P〉0．05）；2组因经济原因和毒副作用原因退出治疗的发生率无显著性差异（P〉0．05），Ⅱ组的一般副作用发生率高于Ⅰ组（P〈0．05）。结论OXC单药治疗国人新诊断的SPS，CPS，SGS的控制率优于作为辅加药物治疗癫癎，2组总有效率无显著性差异，初始目标剂量和退出治疗的发生率相近；OXC毒副作用相对较少、治疗范围大、用药和换药方便；在辅加治疗组患者对OXC的价格的承受力呈下降的趋势。     

Effects of dextropropoxyphene on the steady-state kinetics of oxcarbazepine and its metabolites

The effects of dextropropoxyphene on the steady-state kinetics of oxcarbazepine and its metabolites were investigated in eight patients with epilepsy or trigeminal neuralgia. One patient dropped out of the study, presumably due to side-effects of dextropropoxyphene. Dextropropoxyphene did not affect the plasma levels of the principal active metabolite, 10,11-dihydro-10-hydroxy-carbamazepine. Since dextropropoxyphene is known to increase the plasma levels of carbamazepine, leading to toxicity, the findings of this study suggest that oxcarbazepine is a useful alternative to carbamazepine when concomitant dextropropoxyphene therapy is required.