A comparative evaluation of pharmacokinetics of conventional and slow-release carbamazepine formulation in newly treated patients of epilepsy: a random evaluation. Multiple-dose pharmacokinetic study with a slow-release carbamazepine preparation. Pharmacokinetic evaluation of twice-daily extended-release carbamazepine (CBZ) and four-times-daily immediate-release CBZ in patients with epilepsy. Reduction of dosing frequency of carbamazepine with a slow-release preparation. Treatment of epilepsy in mentally retarded patients with a slow-release carbamazepine preparation. Conventional vs controlled-release carbamazepine: a multicentre, double-blind, cross-over study. Monotherapy with conventional and controlled-release carbamazepine: a double-blind, double-dummy comparison in epileptic patients. Differences in side effects between a conventional carbamazepine preparation and a slow-release preparation of carbamazepine. Controlled release carbamazepine: cognitive side effects in patients with epilepsy.
Study was conducted to compare the pharmacokinetic profile of conventional and slow-release carbamazepine formulations in Indian epileptic patients. Twenty consecutive untreated patients of partial seizures were randomly assigned to receive either conventional carbamazepine (200 mg thrice a day) or slow-release carbamazepine formulation (200 mg thrice a day), 10 patients in each group. The serum carbamazepine concentrations were measured on 10th day and 20th day of treatment. The blood samples were collected before the morning dose. In the conventional treatment group five patients experienced side effects as compared to two in the slow-release group. On 10th day mean serum carbamazepine levels were significantly higher in conventional group (8.27 +/- 1.39 micrograms/ml) in comparison to slow release group (4.28 +/- 3.89 micrograms/ml). The difference was statistically significant (p < 0.05). On 20th day carbamazepine levels fell significantly in conventional group only (8.27 +/- 1.39 micrograms/ml to 5.76 +/- 2.32 micrograms/ml, p < 0.05). At this stage the difference in mean carbamazepine levels of two groups became insignificant (p < 0.05). In conclusion, controlled release formulations provide more steady serum concentrations of carbamazepine along with better tolerability. The pharmacokinetics, clinical efficacy and side effects of carbamazepine (CBZ) in the steady-state condition were studied using a slow-release preparation (SR), Neurotol Slow, and a conventional preparation (C), Tegretol. Eighteen adult epileptic patients under CBZ therapy were evaluated in this single-blind, randomized cross-over study. The previous daily CBZ dose was kept unchanged and divided into 2 daily doses during two 2 week study periods. At the end of each period blood samples were drawn at frequent intervals for 12 h after the administration of the morning CBZ dose. Serum concentrations of unchanged CBZ and its main metabolite, carbamazepine-10,11-epoxide (CBZE), were determined by HPLC. Peak concentrations of CBZ and CBZE were significantly lower, and the time-lapse before CBZ reached its peak was significantly longer during SR treatment. The fluctuations in serum CBZ and CBZE were significantly lower during SR treatment. There was no significant difference in bioavailability between the 2 preparations. The number of epileptic seizures was 31 during SR and 57 during C treatment. Side effects were more common during C treatment. The occurrence of dizziness was significantly lower with SR treatment than with C treatment. We conclude that greater stability in serum CBZ and CBZE concentrations can be obtained by using an SR of CBZ, without reducing the bioavailability of the drug. A new capsule dosage form of carbamazepine (CBZ) has been developed, consisting of three different types of beads (immediate-release, extended-release, and enteric-release) that may be taken sprinkled on food or swallowed for easy administration. We compared the pharmacokinetics of the extended-release dosage form of CBZ (Carbatrol capsules) twice daily with the conventional immediate-release formulation of CBZ four times daily.
                The randomized, double-blind, two-way, cross-over study was conducted at two sites, with a planned sample size of 24 adult patients with epilepsy. Each treatment was administered for 2 weeks. At the end of the 2-week period, blood samples were obtained hourly for a 24-h period.
                The 90% confidence intervals (CI) of the ratio of the means of the extended-release formulation twice daily to the immediate-release formulation four times daily were within the range of 0.80-1.25 for each of the pharmacokinetic parameters for CBZ and for the summation of CBZ and CBZ-epoxide (CBZ-E). There was no difference in the frequency of seizures between treatment (p = 0.103).
                Our results demonstrate that extended-release CBZ twice daily was bioequivalent to immediate-release CBZ four times daily, with regard to CBZ levels and summation of CBZ and CBZ-E levels, based on the pharmacokinetic parameters evaluated. Substituting one formulation for the other did not cause patients to have a significant change in seizure frequency. The occurrence of side effects and epileptic seizures and the pharmacokinetics of carbamazepine (CBZ) and carbamazepine-10,11-epoxide were studied using a slow-release CBZ preparation, Neurotol slow, and a conventional CBZ preparation, Tegretol. The study was an open, randomized cross-over trial, with a 2 week study period for each preparation. Tegretol was given 3 times and Neurotol slow twice a day. The earlier CBZ dose was kept unchanged. The initial sample consisted of 24 adult epileptic patients receiving CBZ treatment of whom 20 patients were evaluable. The fluctuation in serum CBZ concentrations did not differ significantly between the 2 treatment periods, even though the interdose interval of Neurotol slow was 4 h longer than that of Tegretol. The switch-over from conventional CBZ to the slow-release formulation did not seem to alter the efficacy and side effects of CBZ. By using Neurotol slow instead of a conventional CBZ preparation, Tegretol, it is evidently possible to reduce the dosing frequency from 3 times a day to twice daily administrations. Pharmacokinetic properties and efficacy of a conventional (C) carbamazepine (CBZ) preparation divided into three daily doses and a slow-release CBZ preparation (SR) divided into two daily doses were evaluated in a randomized, double-blind, cross-over study. The trial started with a 8-week baseline period followed by the two treatment periods each 10 weeks long. At the end of each period, a 24-h blood sample series for determination of serum CBZ and carbamazepine-10,11-epoxide (CBZE) was collected. The occurrence of seizures was monitored day and night during the whole study period by experienced nurses. The mean age of the 20 evaluable patients was 24.9 and the duration of epilepsy 19.2 and carbamazepine treatment 7.0 years. The bioavailability of CBZ from the two preparations was similar. The mean fluctuation of serum CBZ concentration (Cmax-Cmin/Css) was 16% smaller during SR. The mean serum CBZ concentration in the morning samples was significantly (P less than 0.001) higher during SR treatment. The mean total number of seizures was approximately four per week and did not differ between the two treatments, but during the last 2 weeks of the study period the occurrence of seizures was significantly smaller during SR (P = 0.02). The tolerability and pharmacokinetics of a new controlled-release (CR) formulation of carbamazepine (CBZ), were assessed in a multicentre, double-blind, cross-over trial, carried out in 48 epileptic patients (21 men, 27 women; mean age 34.2 years) on conventional CBZ monotherapy, but without complete seizure control (n = 22) or with intermittent side effects (n = 4), or with both (n = 22). Eligible patients were randomized to conventional CBZ or CR CBZ, each given in sequence at individualized daily doses, subdivided into the lowest number of administrations. Each period of the cross-over consisted of a first phase of optimal dose finding (lasting up to two months) and a second one of maintenance (lasting one month) used for evaluation. At the end of each period, a 10-h plasma CBZ and CBZ-epoxide concentration profile, as well as the tolerability and the efficacy of the drugs, were evaluated. The mean CBZ daily dose increased by 16% during the administration of the CR formulation. Fluctuations of total CBZ and 10, 11-epoxide plasma level daily profiles at steady-state were significantly (p less than 0.001) lower during CR CBZ treatment, leading to a significant (p less than 0.001) decrease in intermittent side effects (6 patients on CR CBZ vs 26 on conventional CBZ). Finally, 38 patients on CR CBZ (vs 15 patients on conventional CBZ) were treated with a b.i.d. regimen. 1. Twenty-one epileptic patients completed a double-blind, double-dummy, random order, crossover comparison of conventional carbamazepine (CBZ, Tegretol, Ciba-Geigy) with a new controlled-release formulation (CBZ-CR, Tegretol Retard). All participants were stabilised on maximally tolerated doses of CBZ as monotherapy (one twice daily, twelve three times daily, eight four times daily). Each preparation was taken with a matched placebo of the other for 4 weeks. 2. Peak serum CBZ concentrations (mean +/- s.e. mean) were lower (CBZ 11.4 +/- 0.4 mg l-1; CBZ-CR 10.4 +/- 0.5 mg l-1; P less than 0.01) and times to peak longer (CBZ 3.6 +/- 0.5 h, CBZ-CR 5.2 +/- 0.7 h, P less than 0.01) during CBZ-CR treatment. Mean CBZ concentrations, however, were also slightly reduced with the new formulation (CBZ 9.9 +/- 0.3 mg l-1; CBZ-CR 9.1 +/- 0.5 mg l-1, P less than 0.05) and this was associated with greater seizure frequency (CBZ 2.8 +/- 1.2, CBZ-CR 3.8 +/- 0.9; P less than 0.05) during the CBZ-CR treatment phase. 3. Diurnal fluctuations (CBZ 41 +/- 3%, CBZ-CR 28 +/- 2%, P less than 0.01) and variations (CBZ 53 +/- 5%, CBZ-CR 33 +/- 3%; P less than 0.01) in serum CBZ concentration were substantially less with CBZ-CR and were similar to those calculated during a 6 or 8 hourly dosage interval with conventional CBZ (fluctuation 33 +/- 3%, variation 42 +/- 5%).(ABSTRACT TRUNCATED AT 250 WORDS) The aim of this double-blind cross-over study was to investigate whether side effects of carbamazepine (CBZ) could be reduced by using a slow-release CBZ preparation. Twenty-one adult patients with epilepsy who had side effects related to the use of CBZ took part in the trial. Patients were randomized to receive either a conventional (C) or slow-release (SR) CBZ preparation for 3 months and were then switched over to the other preparation for another 3 months. The daily dose and dosing frequency of CBZ were kept the same as before the study. The quality and severity of side effects were assessed monthly using a scored questionnaire containing questions about systemic toxicity (STRS) and neurotoxicity (NTRS). Twenty patients could be evaluated. The mean total values of NTRS of 3 monthly visits on each drug were significantly less during SR than during C treatment (P less than 0.05). All the items of NTRS scored lower during SR therapy, and the difference was significant for the occurrence of headache, dizziness and disturbances of vision, speech and coordination. The total score of STRS was also lower during SR, but the difference was not significant. Eleven patients preferred SR, 3 preferred C and 6 patients estimated the periods to be equal. In conclusion, a slow-release preparation of CBZ can render fewer side effects than conventional CBZ preparations. The treatment of epilepsy with carbamazepine (CBZ) may be hampered by cognitive side effects. These side effects are thought to be related to pharmacokinetic properties of the drug. The serum concentration of CBZ is characterized by rapid absorption and a short half-life, which may lead to a considerable fluctuation of the level between doses. Cognitive defects may result from peak levels: short periods with high serum concentration. In a single-blind crossover design, cognitive performance was compared in three conditions. All patients were first tested in the steady state of conventional CBZ. The patients were then assigned randomly to either CBZ-controlled release (CR) or a condition in which conventional CBZ was administered in the same tablet form and dose frequency as CR. Psychological tests were administered four times daily, immediately after the serum samples were taken. A nonmedication control group was tested following the same test scheme to obtain standards for the evaluation of changes in performance during the day. A systematic tendency was found toward higher test performance in the CR condition. This is especially evident for tests of memory and accuracy of visual information processing. The results of the repeated test procedure show that the smoothing effect of the CR condition on serum concentration fluctuations results in a more stable pattern of cognitive functioning during the day.