Carbamazepine levels in head hair of patients under long-term treatment: a method to evaluate the history of drug use

Carbamazepine (CBZ) concentrations were determined in the sections of head hair from 40 patients (22 males and 18 females), ages 5 to 81, who were receiving this drug systemically. Hair treatment included dissolution, liquid phase extraction procedures, and immunoassay (Abbott TDx) or high-pressure liquid chromatography (HPLC) analytical techniques. The mean values of CBZ levels in the hair from the 1st section (close to hair root) to the 5th section for female patients were 26.82, 19.18, 17.28, 15.09, and 14.62 micrograms/g according to HPLC measurements. Immunoassay gave generally slightly higher results. The mean values of CBZ in the hair sections according to the immunoassay technique were 30.53, 21.90, 19.83, 17.45, and 16.99 micrograms/g, respectively, from the 1st to the 5th sections. The corresponding mean values for male patients by HPLC and immunoassay techniques were 21.97, 17.30, 15.03, 13.02, and 11.21 micrograms/g and 25.98, 20.52, 17.15, 14.87, and 12.31 micrograms/g. Generally, a reduction of drug concentrations in hair from the first to the subsequent segments was observed. Higher amounts of CBZ were deposited in black, untreated hair (e.g., not dyed or permed). CBZ concentrations in hair sections were found to be dependent on the dosage (r = 0.979, p < or = 0.001) but not on the gender. The data indicate the possible use of hair section testing as a marker of the dosage history and the compliance of patients under long-term treatment with CBZ.     

Approaches to lung cancer treatment using the CD3 x EGP-2-directed bispecific monoclonal antibody BIS-1

OBJECTIVES: To evaluate the clinical importance of the interaction between carbamazepine (CBZ) and dextropropoxyphene in elderly patients. METHODS: All patients (n = 7263) in Gothenburg, Sweden, who were part of a drug-dispensing programme, were included in the study. Eight per cent of the patients took CBZ and 18% took dextropropoxyphene, continuously. Patients who used a combination of these drugs were compared with patients who took only CBZ or dextropropoxyphene or neither of the two drugs. These four groups of patients were matched to each other with reference to gender, age and concomitant medication, which finally resulted in 21 patients in each group. A questionnaire with 30 symptoms of well-being, including symptoms typical of adverse effects of CBZ, were answered by the patients with the help of a registered nurse. Venous blood samples were drawn from the patients for the analysis of CBZ, its metabolite CBZ 10,11-epoxide (CBZ-E) and dextropropoxyphene. RESULTS: The doses of CBZ and dextropropoxyphene were lower among patients who used the combination of the two drugs than among those who only used one of the drugs. The mean level of CBZ in serum (S-CBZ) was, however, significantly higher and the level of CBZ-E in serum (S-CBZ-E) significantly lower among the patients who used the combination of CBZ and dextropropoxyphene, thus indicating an inhibition of the metabolism of CBZ. The prevalence of symptoms indicating side effects of CBZ was significantly higher in the group of patients who used both drugs. CONCLUSION: This study has shown that the combination of CBZ and dextropropoxyphene is hazardous in elderly patients and should be used with caution.     

Carbamazepine and its metabolites in human perfused placenta and in maternal and cord blood

Placental transfer and metabolism of carbamazepine (CBZ) was studied in a dual recirculating placental cotyledon perfusion system and was also evaluated in 16 pairs of maternal venous and cord blood samples. Among the parameters studied as possible indicators of a successful perfusion, volume changes in perfusate divided the perfusions into two groups, whereas no significant differences between perfusions were noted in blood gas analysis or in antipyrine transfer. CBZ added into the maternal circulation crosses the placenta in the beginning quicker than antipyrine which is in agreement with the different lipid solubilities of these compounds. Because the transfer rates of antipyrine and CBZ were about the same, the mechanism of transfer of CBZ is probably similar to that of antipyrine (passive diffusion). No metabolites of CBZ could be detected in the perfusate by high-performance liquid chromatography (HPLC) or gas chromatography/mass spectrometry. With the improved HPLC methodology for CBZ metabolites, six metabolites were detected in clinical samples, including 10-hydroxy-10,11-dihydro-CBZ (10-OH-CBZ), which has been described earlier in only 1 uremic patient. Relative levels of metabolites showed significant individual differences. CBZ crosses perfused placenta rapidly, but this does not contribute to CBZ metabolites detected in maternal and fetal circulation.     

Simultaneous liquid chromatographic analysis for carbamazepine and carbamazepine 10,11-epoxide in plasma and saliva by use of double internal standardization

High-performance liquid chromatography (HPLC) was used for simultaneous quantitation of carbamazepine (CBZ) and carbamazepine 10,11-epoxide (CBZ-EP) in plasma and saliva. Because concentrations of CBZ can greatly exceed those of CBZ-EP after single doses, two internal standards, lorazepam and N-desmethyldiazepam were added to all samples. Following extraction with chloroform, the components are separated on a muBondapak CN column with a mobile phase composed of 30% acetonitrile in water. Total chromatography time in 10 min. Concentrations of CBZ and CBZ-EP as low as 18 and 56 ng/ml, respectively, can be detected using 0.5 ml of plasma or saliva. The maximum within-day and day-to-day coefficients of variation for both compounds are 6.3 and 7.0%, respectively. Specificity of the method was supported by a significant correlation (r = 0.99) between assay results of the present method and those of a previously published HPLC assay. Application of the method to protein binding and salivary measurements in a single-dose CBZ disposition study is demonstrated.     

Probing the native strain iin alpha1-antitrypsin

OBJECTIVE: To study the relationship between the plasma concentration of stiripentol (STP), a new antiepileptic drug, and its inhibitory effect on the formation of carbamazepine epoxide (CBZE) in epileptic children treated with carbamazepine (CBZ) either alone or in combination with another antiepileptic drug. METHODS: Minimum plasma concentration of antiepileptic drugs was measured before initiation of STP therapy (day 0) and on days 28 (STP 60 mg.kg-1.day-1) and 84 (STP 90 mg.kg-1.day-1) by HPLC. RESULTS: The CBZE/CBZ plasma concentration ratio decreased exponentially with increasing minimum plasma STP concentration (r = 0.80). The asymptote of the curve allowed the calculation of the minimum plasma STP concentration required to obtain the maximum inhibitory effect, i.e. 6.7 mg.l-1. CONCLUSION: The inhibitory effect of STP on CBZ metabolism expressed as the CBZE/CBZ plasma concentration ratio is dependent on STP plasma concentration, with a maximum effect at an average of 7 mg.l-1. The present data suggest that in order to evaluate the anticonvulsant efficacy of STP as add-on therapy, the minimum plasma STP concentration should be maintained above 7 mg.l-1 and the dosage of CBZ should simultaneously be decreased in steps by more than 50% to minimize the change in CBZ plasma concentration.     

A single and multiple dose bioavailability study with carbamazepine 400 mg retard tablets with reference to enzyme autoinduction and circadian time differences

Both single and multiple dose bioequivalence studies are required to assess the quality of modified release formulations of drugs. In bioequivalence studies of drugs with enzyme autoinducing properties such as carbamazepine (CBZ), the standard multiple dose study design must be modified to guarantee equivalence of drug elimination. This problem was considered with regard to carbamazepine 400 retard AWD (test) whose bioavailability relative to a listed reference (Tegretal 400 retard) was studied in 2 randomized, open, crossover studies both with 18 healthy volunteers of Caucasian origin (20-36 years, 61.5-92 kg, 172-195 cm). The single dose study was done with 400 mg CBZ. Serum concentration time profiles of CBZ and its active metabolite CBZ-10,11-epoxide were determined until 144 h after administration. The multiple dose study was performed with 400 mg CBZ b.i.d. for 15 days (first 2 days: 200 mg b.i.d.) followed by a 7-day study with the alternative investigational product. 24-hour serum concentration time profiles of CBZ and its metabolite were measured on days 15 and 22 of the study. The quantitative drug analysis was done with an HPLC method the quality of which fulfilled the requirements of bioequivalence studies. Test was considered bioequivalent to reference with regard to the extent of absorption, if the 90% confidence intervals of the AUC0-infinity ratio (single dose) and AUC0-24h ratio (multiple dose) were within the range of 0.80-1.25, and with regard to rate of absorption if the 90% confidence intervals of the Cmax/AUC ratio (single dose) or AUCF0-24h ratio were within 0.70-1.43. The point estimators (90% confidence limits) of the AUC ratio (test/reference) of CBZ were 0.979 (0.94, 1.02) for the single and 1.01 (0.947, 1.076) for the multiple dose comparison. The point estimator (90% confidence limits) of the Cmax/AUC ratio was 0.989 (0.959, 1.020) and of the AUCF0-24h ratio 1.066 (0.937, 1.212). There were no circadian time differences in any pharmacokinetic parameter. In conclusion: Carbamazepine 400 retard AWD tablets were bioequivalent to reference with regard to extent and rate of absorption after both single and multiple dose administration.     

Carbamazepine-10,11-epoxide in therapeutic drug monitoring

Carbamazepine (CBZ) is widely used in the treatment of epilepsy, frequently in combination with other anticonvulsants. Its metabolite, carbamazepine-10,11-epoxide, is pharmacologically active and is increased with concurrent use of valproate and other anticonvulsants. This pharmacokinetic interaction may be particularly important because CBZ, its epoxide, phenytoin, and lamotrigine all act on fast voltage-dependent sodium channels. Over a 2-month period, routine serum requests for CBZ (n=47) (excluding known cases of overdose) were also analyzed for CBZ epoxide, phenytoin, and lamotrigine using a simultaneous high performance liquid chromatographic (HPLC) method. Valproate was measured using fluorescence polarization immunoassay (FPIA). With concurrent phenytoin and lamotrigine administration, there was a relative increase in CBZ epoxide and a significant decrease in the ratio of CBZ to epoxide (from more than 5 to 3). If valproate was also present, the concentration of parent and metabolite increased significantly, causing potential toxicity. Two patients in this latter group had significant clinical toxicity, with parent CBZ concentrations in the reference range; a third patient suffered from poor control of seizures. This study illustrates the importance of awareness of the contribution of active metabolites in therapeutic drug monitoring and raises questions about the role of the routine monitoring of such metabolites.     

Carbamazepine intoxication with negative myoclonus after the addition of clobazam

We report a case a carbamazepine (CBZ) intoxication with negative myoclonus that occurred 4 weeks after clobazam (CLB) had been added to a stable regimen of CBZ and topiramate (TPM). Both CBZ and CBZ-epoxide (CBZ-E) blood levels were elevated, and the symptoms resolved quickly when CBZ dosage was reduced and CLB discontinued. CLB was reintroduced a year later with the patient's consent, and the time course of the interaction was studied: CBZ and CBZ-E levels increased slowly over 12 days. The interaction is thus probably related to the progressive increase in Nor-CLB.     

Determination of diarrheic shellfish toxins in mussels by microliquid chromatography-tandem mass spectrometry

Treatment of cultured bovine adrenal medullary cells with carbamazepine (CBZ) for 5 days caused an increase in catecholamine secretion induced by veratridine, an activator of voltage-dependent Na+ channels. However, no increase was stimulated by carbachol, an agonist of nicotinic receptors, or by 56 mM K+, a depolarizing agent that activates voltage-dependent Ca++ channels. CBZ (30 microg/ml) treatment enhanced veratridine-induced catecholamine secretion in a time-dependent manner (increases of 25%, 65% and 70% for 3, 5 and 7 days of treatment, respectively). CBZ treatment (5 days) increased veratridine-induced catecholamine secretion in a concentration-dependent manner (increases of 27%, 36%, 45% and 55% at 10, 15, 20 and 30 microgram/ml of CBZ, respectively). CBZ treatment also increased 22Na+ influx and 45Ca++ influx stimulated by veratridine. The stimulatory effect of CBZ treatment on catecholamine secretion was blocked by either actinomycin D or cycloheximide, an inhibitor of protein synthesis. Additive responses of catecholamine secretion and 22Na+ influx induced by veratridine were associated with combined exposure of the cells to CBZ and dibutyryl cyclic AMP. CBZ treatment (30 microg/ml, 5 days) significantly increased the specific binding of [3H]saxitoxin to cell membranes. A Scatchard analysis of [3H]saxitoxin binding revealed that CBZ increased the Bmax value without any change in the dissociation constant. These findings suggest that CBZ up-regulates the density and activity of voltage-dependent Na+ channels.     

Carbamazepine in the treatment of cocaine dependence: Subtyping by affective disorder.

Studies investigating carbamazepine (CBZ) in the treatment of cocaine dependence have been inconsistent. In this study, cocaine-dependent individuals with (n=57) and without (n=82) affective disorder were compared in a 12-week, double-blind, placebo-controlled trial. Urine drug screens (UDS) and self-report of drug use were collected weekly. Affective symptoms were measured monthly. Subjects receiving CBZ attended more medication sessions (p=.03). The CBZ-treated affective group had a trend toward fewer cocaine-positive UDS (p=.08) and a significantly longer time to first cocaine use (p=.06). CBZ treatment did not have any impact on cocaine use in individuals without affective disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Physical workload and the aging worker: a review of the literature

In two groups of epileptic children receiving carbamazepine (CBZ) therapy with or without valproic acid (VPA) comedication, we investigate the drug interactions of VPA on serum CBZ and its metabolites' concentrations, concentration ratios, and level/dose ratios. Serum total and free CBZ-10, 11-epoxide (CBZ-E) concentrations are significantly increased in patients taking CBZ plus VPA, together with higher CBZ-E/CBZ concentration ratios and CBZ-E level/dose ratios. These results reflect the accumulation of CBZ-E. The decreased concentration ratios of trans-10, 11-dihydroxy-10, 11-dihydro-CBZ (CBZ-H)/CBZ-E observed in patients taking CBZ plus VPA suggest an inhibition in the biotransformation from CBZ-E to CBZ-H. Significant negative correlations are found between serum VPA level and CBZ-H/CBZ-E concentration ratios, indicating that the inhibition of CBZ-E hydrolysis by VPA may depend on the concentration of VPA (total or free CBZ-H/CBZ-E concentration ratio = [formula: see text], respectively). VPA concentration also shows significant positive correlations with CBZ-E and CBZ level/dose ratios. Patients taking CBZ plus VPA have significant higher free fractions of CBZ and CBZ-E than do patients on CBZ alone, suggesting a protein-binding displacement by VPA.     

Adjustment of carbamazepine dose to offset the effects of the interaction with remacemide hydrochloride in a double-blind, multicentre, add-on drug trial (CR2237) in refractory epilepsy

PURPOSE: The efficacy of remacemide hydrochloride (REM) as an antiepileptic drug (AED) was tested in a double-blind, add-on trial in patients with refractory epilepsy. Concurrent drugs included carbamazepine (CBZ). The interfering effects of the pharmacokinetic interaction between REM and CBZ were offset by the monitoring of plasma CBZ concentration and the appropriate reduction of CBZ dose by an unblinded observer. METHODS: Patients taking CBZ entered a 4-week run-in period to stabilise their dosage regimen to Tegretol tablets and blinded capsules containing Tegretol tablets. They then entered an 8-week baseline period during which variation of plasma CBZ concentration was used to derive an individual Shewart Control Chart for each patient. These charts were used to define the threshold for CBZ dose reduction after the addition of trial drug. Where necessary the unblinded observer adjusted that portion of the daily dose of CBZ concealed in the opaque capsules, thereby maintaining the blind for the investigator and the patient. RESULTS: CBZ dosage reductions ranging from 14 to 50% were required by 63% of patients who received REM. Substantial increases in plasma CBZ concentration, which would have confounded the results of the trial, were thus avoided. The small increases in CBZ concentration that occurred in spite of this procedure were of similar magnitude in responders (patients who experienced > or =50% reduction in seizure frequency during treatment) and nonresponders, and in both groups the mean increase was <1 mg/L. CONCLUSIONS: The method is offered as a model solution for problems caused by pharmacokinetic interactions in add-on trials.     

Clarithromycin-carbamazepine interaction: a case report

We report a clinically relevant interaction between a new macrolide antibiotic, clarithromycin, and carbamazepine (CBZ). In a patient receiving CBZ monotherapy, 10-day antibiotic treatment increased CBZ concentration despite concomitant CBZ dose reduction and doubled the CBZ concentration/dose ratio. Concentration of the CBZ epoxide (CBZ-E) metabolite was reduced, suggesting that the interaction occurs at a metabolic level.     

Carbamazepine-induced tics

A variety of movement disorders are known to occur in association with carbamazepine (CBZ) therapy in adults and children, but development of tics has been described infrequently and only in patients with underlying Tourette's syndrome or other movement disorders. We report 3 children with epilepsy who developed facial motor tics after initiation of CBZ for complex partial seizures. All 3 had documented CBZ blood levels in the therapeutic range at the time, and none had other symptoms or signs of clinical intoxication. Neurologic examinations were normal in 2 and showed developmental delay of expressive language in the third. Brain imaging was normal in all. After development of the tics in 2, CBZ was continued at the same or higher dose, and the tics abated and then ceased spontaneously < or = 6 months. In the third child, the tics ceased after CBZ discontinuation. These cases demonstrate that CBZ can induce simple motor tics in children. These idiosyncratic reactions may be transient and do not always necessitate drug discontinuation.     

Carbamazepine reduces dopamine-mediated behavior in chronic neuroleptic-treated and untreated rats: Implications for treatment of tardive dyskinesia and hyperdopaminergic states.

Chronic treatment with neuroleptic drugs such as haloperidol (HAL) can result in a syndrome of abnormal involuntary movements known as tardive dyskinesia (TD). The authors have obtained evidence that TD in humans is reduced in patients also taking anticonvulsant drugs, primarily carbamazepine (CBZ). To test for a causal role of CBZ in this effect, the authors quantified abnormal movements elicited by dopamine (DA) receptor stimulation in rats (Rattus norvegicus) withdrawn from chronic treatment with HAL or CBZ alone or in combination. The expected increased behavioral responsiveness to combined D1/D2 stimulation in rats treated with HAL for 8 weeks was significantly attenuated by chronic CBZ, which also attenuated behavioral responsiveness in otherwise untreated rats. Striatal D2 DA receptor density was elevated in rats treated chronically with HAL but unaffected by CBZ. Striatal D1 DA receptor density was elevated by chronic CBZ but unaffected by HAL. These findings suggest that by reducing DA supersensitivity, CBZ may be useful in treating TD and other hyperdopaminergic states. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Carbamazepine-induced release of serotonin from rat hippocampus in vitro

PURPOSE: Carbamazepine is one of several antiepileptic drugs (AEDs) that release the inhibitory neurotransmitter serotonin as part of their pharmacodynamic action on brain neurons. We undertook this study to investigate the cellular processes by which carbamazepine (CBZ) releases serotonin from brain tissue. METHODS: Tissue slices were prepared from hippocampi of Sprague-Dawley rats. These hippocampal slices were preincubated in vitro in a buffer so that neurons within the slice would take up tritium-labeled serotonin. Subsequently the slices were superfused with buffer containing CBZ or other chemicals (or both) that increase the overflow of serotonin radioactivity. RESULTS: Carbamazepine produced a concentration-dependent (50, 125, 250, or 500 microM) increase in basal overflow of serotonin radioactivity from superfused rat hippocampal slices in vitro. In contrast, these concentrations did not alter potassium-stimulated release, suggesting that the CBZ-induced release does not depend on depolarization or exocytosis. Blockade of the neuronal membrane serotonin transporter by fluoxetine (1 microM) or citalopram (2 microM) did not alter overflow of serotonin radioactivity produced by 250 microM CBZ. p-chloramphetamine (10 microM) produced a substantial increase in overflow of serotonin radioactivity, and this effect appears to be antagonized by 250 microM CBZ. Uptake of [3H]-labeled serotonin into hippocampal synaptosomes was inhibited by CBZ with a median inhibitory concentration (IC50) of 511+/-33 microM and a Hill coefficient of 0.87+/-0.11, suggesting competitive inhibition of uptake by CBZ. CONCLUSIONS: We conclude that CBZ (a) releases serotonin from hippocampal slices independent of exocytosis and by a mechanism not involving the neuronal membrane serotonin transporter, and (b) at high enough concentration, blocks the neuronal serotonin transporter.     

Pantoprazole does not interact with the pharmacokinetics of carbamazepine

OBJECTIVE: Pantoprazole is a H+/K+-ATPase inhibitor with a minimized potential of interaction with the cytochrome P450 system. Imidazole derivatives such as cimetidine and omeprazole have been shown to markedly interact with carbamazepine, a major anticonvulsant with a narrow therapeutic range. Therefore, the influence of steady-state pantoprazole on the pharmacokinetics of carbamazepine was investigated. SUBJECTS AND METHODS: N = 20 healthy volunteers (12 male/8 female) completed a double-blind, placebo-controlled, randomized crossover study. During the test period they received 40 mg pantoprazole p.o. once daily for 11 days and concomitantly a single oral dose of 400 mg carbamazepine on day 5. In the reference period placebo was administered instead of pantoprazole. RESULTS: Serum concentrations of carbamazepine and its active metabolite carbamazepine-10,11-epoxide were measured until day 11. Geometric means of AUC (extent characteristic) and Cmax/AUC (rate characteristic) of carbamazepine were 292 and 287 mgxh/l, and 0.0150 and 0.0144 l/h (reference and test), respectively. Point estimates and 90% confidence intervals of the ratios were 0.98 (0.95, 1.01) for AUC, and 0.96 (0.92, 1.00) for Cmax/AUC, respectively. Since the 90% confidence intervals of the primary characteristics, AUC and Cmax/AUC were entirely within the predefined equivalence range of 0.80 - 1.25, lack of interaction of pantoprazole with the pharmacokinetics of carbamazepine was demonstrated. Equivalence was also demonstrated for carbamazepine-10,11-epoxide using the characteristics AUC and Cmax. CONCLUSION: No dose adjustment of carbamazepine is therefore required during concomitant treatment with pantoprazole.     

Pharmacological protection of CNS white matter during anoxia: actions of phenytoin, carbamazepine and diazepam

The effects of phenytoin (DPH), carbamazepine (CBZ) and diazepam (DZP) on anoxia-induced injury in CNS white matter were studied using the in vitro rat optic nerve preparation. Optic nerves were subjected to 60 min of anoxia and functional recovery was assessed using the area under the compound action potential. Under normoxic conditions, application of DPH, CBZ and DZP reduced compound action potential area over concentration ranges known to block sodium channels. All three compounds, however, protected against anoxic injury at concentrations below those that inhibited the normoxic compound action potential. Thus, the application of 1 microM DPH, CBZ or DZP during anoxia resulted in compound action potential recovery to 60.0, 53.8 and 69.2% of control, respectively, compared to compound action potential recovery of 34.8% in the absence of drugs (P < .05 in all three cases). In the cases of CBZ and DPH, 60% improvement in recovery from anoxia was produced by concentrations well below those employed clinically to treat epilepsy, suggesting a potential role for these drugs in the protection of CNS white matter from anoxic injury.     

Effects of humidity and temperature on in vitro dissolution of carbamazepine tablets

The rate and extent of dissolution of various approved marketed carbamazepine (CBZ) tablets exposed to 33, 52, 75, and 97% relative humidities at both room temperature and 40 degrees C, and saturated water vapor at room temperature were compared to fresh unstressed tablets. The dissolution data indicate that exposure of CBZ tablets to high humidity and temperature can have a profound effect on tablet disintegration and dissolution. The dissolution rates of some batches of CBZ products exposed to 97% humidity at 40 degrees C or saturated water vapor at room temperature were drastically reduced in only 6-7 days.     

Importance of dissolution process on systemic availability of drugs delivered by colon delivery system

The relationship between in vitro drug release characteristics from colon delivery systems and in vivo drug absorption was investigated using three kinds of delayed-release systems. 5-aminosalicylic acid (5-ASA), tegafur (FT) and carbamazepine (CBZ) were selected as model drugs. Pressure-controlled colon delivery capsules (PCC) for liquid preparations, time-controlled colon delivery capsules (TCC) for liquid and solid preparations and Eudragit S coated tablets for solid preparations were used in this study. At first, in vitro dissolution tests for all preparations were performed. Drug release from solid preparations was delayed compared to that from liquid preparations with all three drugs. Next, these preparations were administered to fasted beagle dogs. For 5-ASA, the mean Cmaxs (peak level) of Eudragit S coated tablets and PCC were 5.52 and 16.89 micrograms ml-1, respectively. The mean Tmaxs (time when drug reached peak level) were 3.0 and 5.3 h. AUCs were 22.57 and 48.09 micrograms.h ml-1, respectively. For FT, Cmaxs of Eudragit S coated tablet and PCC were 0.87 and 1.46 micrograms ml-1, and Tmaxs were 7.0 and 6.7 h, respectively. AUCs were 9.73 and 15.55 micrograms.h ml-1 and bioavailabilities were 43.79 and 70.84%. For CBZ, the mean Cmaxs of liquid preparations and solid preparations were 0.37 and 0.22 micrograms ml-1, respectively. The mean Tmaxs were 4.7 and 4.3 h. AUCs were 0.673 and 0.392 micrograms.h ml-1. With liquid preparations, drug was thought to contact to the colonic membrane easily because of lack of interference by stools, and to be absorbed well as compared with solid preparations. From these findings, drug release from colon delivery systems and drug dissolution in the colonic lumen are very important factors for the systemic availability of drugs from the colon delivery systems.