Improvement of dissolution properties of Carbamazepine through application of the liquisolid tablet technique

The aim of the work was to improve the dissolution properties of the practically insoluble antiepileptic drug, Carbamazepine (CBZ) by adopting the liquisolid compaction technique. Reported liquid load factors, and excipient ratios were used to calculate the required amounts of excipients necessary to prepare the compacts or tablets according to a mathematical model. Avicel PH 102, and Aerosil 200 were used as the carrier and the coating materials, respectively, and explotab was used as disintegrant to prepare four tablet formulae, out of which formula 1 was successfully compressed into tablets. The dissolution patterns of liquisolid CBZ tablets, carried out according to the USP, were comparable to those of Tegretol^®. The protection of male albino mice against the convulsion, induced by electroshock, was lower in case of liquisolid tablets compared to Tegretol^® suspension and tablets probably due to the precipitation of CBZ in the silica pores resulting from its high dose.     

Pharmacokinetic Evaluation of Twice-Daily Extended-Release Carbamazepine (CBZ) and Four-Times-Daily Immediate-Release CBZ in Patients with Epilepsy

Summary: Purpose: 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.
Methods: 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.
Results: 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).
Conclusions: 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.     

Antiepileptic Drugs in Mood-Disordered Patients

Summary:  Bipolar disorder is a common, recurrent, often severe mental disorder that, without adequate treatment, is associated with high rates of morbidity and mortality. We review the evidence on the efficacy of a spectrum of antiepileptic drugs (AED) in bipolar disorder. Most studies have been carried out with carbamazepine (CBZ), valproate (VPA), and lamotrigine (LTG). All three of these AEDs have been shown to be of value in the management of patients with bipolar illnesses. VPA and CBZ seem to exert stronger antimanic effects and, to a lesser degree, acute antidepressant efficacy. LTG seems to be effective against depression and mania, with a more robust activity against depression. No firm evidence supports a role for vigabatrin, tiagabine, topiramate, or levetiracetam in these disorders.     

Fever as an Adverse Reaction to Carbamazepine

Abstract: Fever as an adverse reaction to carbamazepine. W. P. Sheridan, R. W, King and M. Gerstman. Aust. N.Z. J. Med., 1982, 12 , pp. 520–522.
Two middle-aged women developed fever and abnormal liver function tests while taking carbamazepine. In one case the fever recurred following drug challenge. There are possible links to the known immune-related effects of the drug. Carbamazepine should be considered as a cause if fever or cholestasis develops in any person taking the drug.     

Plasma norepinephrine and left ventricular hypertrophy in systemic hypertension

The relations between some pressure and humoral factors, and some echocardiographic indexes of left ventricular (LV) hypertrophy were studied in 64 patients with essential hypertension. Fifty-seven percent of these patients showed echocardiographic evidence of LV hypertrophy (LV mass greater than 215 g). Multivariate stepwise regression analysis showed that only mean blood pressure (BP) and circulating norepinephrine (NE) levels were significantly related to LV mass index in the group of patients with LV hypertrophy. However, mean BP was the only factor related to LV mass index in the subgroup of patients with LV hypertrophy and plasma NE within the normal laboratory range, whereas NE was the sole factor related to LV mass index in the subgroup with LV hypertrophy and abnormally elevated NE levels (greater than mean + 2 standard deviations of the normal laboratory range). Correlation of LV mass index vs NE was -0.35 (not significant) in the former group of patients and 0.89 (p less than 0.01) in the latter group. NE showed no relation with the echocardiographic variables in the hypertensive patients without LV hypertrophy; in this group, diastolic BP was the only factor related to LV mass index. Circulating NE levels were slightly higher in patients with LV hypertrophy (213 +/- 68 ng/liter) than in those without LV hypertrophy (187 +/- 46 ng/liter), but differences were not significant when adjusting NE for age. Plasma renin activity was not dissimilar in the absence or presence of hypertrophy. In conclusion, our findings suggest that NE might be associated with pressure factors in regulating LV hypertrophy development only in a subgroup of hypertensive patients characterized by echocardiographic LV hypertrophy and abnormally elevated circulating NE levels.     

HPLC法测定卡马西平血药浓度

目的建立反相高效液相色谱法测定人血清中卡马西平(CBZ)血药浓度的方法学。方法血清用乙酸乙酯提取,选择地西泮(Diazepam)为内标,采用Symmetry C18(250mm×4.6mm,5μm)分析柱,流动相为乙腈-水(70:30),检测波长为285nm,流速0.8m L·min-1,柱温35℃。用高效液相色谱法测定CBZ血药浓度。结果 CBZ和内标地西泮的保留时间分别为4.2min,6.3min,分离效果良好,CBZ的血药浓度在1.25~40μg·m L-1范围内呈现良好的线性关系(R=0.9998),平均回收率97.6%,日内RSD<5%。结论本法快速、简便、准确,适合临床常规监测需要。     

Role of calcium in the inotropic effects of caffeine in cardiac Purkinje fibers

The inotropic effects of caffeine (1-3 mM) were studied in the presence and absence of strophanthidin in canine Purkinje fibers perfused in vitro. Caffeine (1 mM) induced a similar initial increase in contractile force in different calcium solutions (+22, +23 and +24% in 0.54, 2.7 and 8.1 mM calcium, respectively) and when propranolol (3.4 X 10(-6) M) was present. Also, caffeine increased contractile force in high potassium (16.2 mM) at a time when the slow action potentials were unaltered. After the increase, 1 mM caffeine decreased force by about 50%, and the decrease was larger when caffeine (3 mM) or [Ca]0 (8.1 mM) was higher. In the presence of caffeine, strophanthidin (3 X 10(-7)-1 X 10(-6) M) increased force (+302%) if caffeine (0.3 mM) and Ca concentrations (0.54 mM) were low. If either caffeine or calcium was increased, strophanthidin had no effect or decreased force. Strophanthidin alone increased force and then decreased it; caffeine increased force in the first stage and decreased it during the second stage. The positive inotropic effect (+224%) of low sodium (78.4 mM versus 149.4 mM in Tyrode solution) was also abolished by caffeine (-24%). In ventricular muscle fibers, caffeine increased force more (+59%) and reduced force less in the presence of strophanthidin. The results indicate that caffeine increases force initially by releasing calcium from intracellular stores. The caffeine-induced decline in force is modulated by calcium in that it is exaggerated by agents or procedures which increase cellular calcium (strophanthidin, high calcium, low sodium solutions) and is reversed in a low calcium solution.     

Surgical treatment of endocardial cushion defects.

A recent surgical experience with the spectrum of atrioventricular (A-V) canal is reviewed. Twenty-five patients underwent surgery for the partial and complete from of this defect in the 4 years from 1971 through 1974. Sixteen had a partial defect, two a transitional defect and seven complete A-V canal. The characteristic murmurs accompanied by cardiac enlargement, pulmonay overcirculation and left axis deviation in the electrocardiogram were sufficient for diagnosis in most cases. Cardiac catherization was performed in all patients preoperatively and in 11 postoperatively. The operative approach, including a double patch modification of the usual repair for complete canal, is considered. Definitive repair, rather than pulmonary arterial banding, is advocated regardless of the patient's age. The operative mortality rate is low in patients with the ostium primum type of defect but is related to associated intracardiac anomalies in those with the complete form of the defect. Residual mitral insufficiency is a common finding after surgical repair of both partial (75 percent) and complete (100 percent) A-V canal. Although no patient in the series died of florid mitral regurgitation, the long-range effects of this complication may lead to mitral valve replacement.     

The effect of bacterial infections on ketone concentrations in rat liver and blood and on free fatty acid concentrations in rat blood.

The concentrations of cytoplasmic lactate and pyruvate and the NAD+/NADH ratio and the concentrations of mitochondrial acetoacetate, beta-hydroxybutyrate, and the NAD+/NADH ratio were determined in normal, fed, and fasted rats, and in rats infected with Streptococcus pneumoniae, Francisella tularensis, and Salmonella typhimurium. The various infections were found to have little or no effect on the cytoplasmic parameters. In normal rats, fasting caused a marked increase in blood and hepatic ketone concentration and in serum free fatty acid content. Fasted infected rats, however, did not show the increase in ketone bodies or serum free fatty acids normally associated with fasting alone. The mitochondrial NAD+/NADH ratio increased as the infections progressed, reversing the normal trend. The introduction of an infection during the fasting state when ketone bodies and serum free fatty acids were elevated caused a marked depression in their concentration. These data have led to a postulation of decreased lipolysis in the infected host to account for the lowered hepatic and blood ketone bodies and the decreased level of serum free fatty acids.     

Early hemoperfusion for emergency treatment of carbamazepine poisoning

Objectives

To investigate the clinical value of early hemoperfusion (HP) in emergency treatment of carbamazepine (CBZ) poisoning.