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At least 685 records · Page 38Linked to original sources
PubMed1992

Acetazolamide improves action myoclonus in Ramsay Hunt syndrome.

The myoclonus of two patients with Ramsay Hunt syndrome was only partially controlled under treatment with clonazepam, sodium valproate, primidone, and piracetam. Acetazolamide (200 mg daily) was added to these drugs, resulting in a dramatic improvement. Placebo substitution (one patient) and withdrawal of acetazolamide in the other patient resulted in marked aggravation of the myoclonus. The mechanism of action of acetazolamide in myoclonus is unknown. Acetazolamide may be an additional therapeutic possibility for patients with severe action myoclonus.

Acetazolamide↗
PubMed1993

Hypersensitivity vasculitis and systemic lupus erythematosus induced by anticonvulsants.

Vasculitis can be a systemic manifestation of hypersensitivity to many drugs, among them anticonvulsants. The clinical manifestations include rash and renal, hepatic, and pulmonary involvement. Diagnosis is based upon clinical findings and a characteristic biopsy showing granulocytic and sometimes eosinophilic infiltrates around small blood vessels, especially venules. A severe form of hypersensitivity vasculitis, with extensive visceral involvement and poor prognosis, has been encountered very rarely following phenytoin and in isolated cases following carbamazepine and trimethadione administration. Drug-induced systemic lupus erythematosus is much more frequent, with distinct clinical and laboratory abnormalities. The syndrome was described following treatment with most anticonvulsants in clinical use--phenytoin, carbamazepine, ethosuximide, trimethadione, primidone, and valproate, but not phenobarbital or benzodiazepines. The early recognition of these syndromes as being related to drugs is important, because they usually remit upon withdrawal of the offending agent.

Anticonvulsants↗
PubMed1979

Decreased phenytoin levels in antineoplastic therapy.

A case history is reported illustrating the difficulties which may be encountered in maintaining seizure control in patients being treated with antineoplastic therapy. The maintenance of therapeutic serum levels of phenytoin during combined cis-platinum and bleomycin sulfate therapy suggests an absorptive defect, possibly related to damage of the intestinal mucosa. This defect did not appear to alter the absorption of primidone or phenobarbital, since increased dosages were not necessary to maintain these drugs within therapeutic ranges.

Adult↗
PubMed1983

Comparison of assay methods used to measure antiepileptic drugs in plasma.

The various techniques used to measure the concentration of antiepileptic drugs in plasma have been compared using data from the HEATH-CONTROL external quality control scheme. Assay methods were categorized as gas-liquid chromatography with and without derivatization (GLC + D, GLC-ND), radio- and enzyme multiplied immunoassay (RIA, EMIT), thin-layer and high-pressure liquid chromatography (TLC, HPLC), and spectrophotometry and colourimetry. The accuracy of the methods was determined from differences of measurements from the levels of drugs spiked into the samples. Most methods significantly underestimated the spiked drug concentrations. Comparisons of assay precision were made with the standard deviation of measurements or from the performance of individual laboratories in a ranking procedure. Comparable significant differences were found in both analyses. RIA followed by GLC-ND were the least variable methods for phenytoin; EMIT and then GLC-ND were the best for both phenobarbitone and primidone. Spectrophotometric measurements of phenobarbitone were unacceptably variable. TLC and colourimetry performed well for carbamazepine, whereas the GLC methods were the most variable. HPLC topped the list for ethosuximide, whereas EMIT had difficulty with this drug. Methods used for valproic acid were similar in precision. GLC + D was consistently less effective for all drugs when compared with GLC-ND.

Anticonvulsants↗
PubMed1983

Application of substrate-labelled fluorescent immunoassay to the measurement of anticonvulsant and antiasthmatic drug levels in plasma and serum.

The use of the Ames homogeneous Substrate-Labelled Fluorescent Immunoassay is described here. It performed easily and accurately across the therapeutic and low toxic ranges with the drugs phenytoin, phenobarbital, primidone, carbamazepine, and theophylline, and also at high toxic levels subsequent to prior sample dilution. The assay performed well in comparison to the standard assays of gas-liquid chromatography, radioimmunoassay, and enzyme immunoassay, and showed no problems with lipaemic, icteric, or, particularly, uraemic specimens.

Anticonvulsants↗
PubMed1984

Systematic comparison of three basic methods of sample pretreatment for high-performance liquid chromatographic analysis of antiepileptic drugs using gas chromatography as a reference method.

Sera of epileptic patients which were routinely examined by gas chromatography (GC) were also analysed using high-performance liquid chromatography (HPLC). Three basic methods for the pretreatment of samples for HPLC analysis were compared: protein precipitation by adding acetonitrile to the serum, direct serum extraction using ethylacetate, and partitioning of serum and buffer solution over a stationary phase and extraction with dichloromethane/2-propanol. The analytical performance and practicability of the three methods were tested under routine conditions. The following anti-epileptic drugs and metabolites were used in the comparison of HPLC with GC: ethosuximide, primidone, phenobarbital, phenytoin, carbamazepine, N-desmethylmethsuximide, and phenylethylmalonediamide.

Anticonvulsants↗
PubMed1984

Automated high-pressure liquid chromatographic assay for antiepileptic drugs and their major metabolites by direct injection of serum samples.

We present a fully automated high-pressure liquid chromatographic (HPLC) assay for simultaneous quantitation of five antiepileptic drugs [ethosuximide (ES), primidone, phenobarbital, phenytoin, and carbamazepine] and their major metabolites [phenylethylmalondiamide (PEMA), carbamazepine-10,11-dihydro-10,11-diol (CBZD), and carbamazepine-10,11-epoxide (CBZE)] in serum samples without sample pretreatment. Two other metabolites, p-hydroxyphenobarbital (HPB) and 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH), can be separated as well. Interference with serum constituents prevents a quantitative determination. Serum samples are injected onto a pre-column, the biological matrix is eluted with water, and the compounds of interest are subsequently separated on an analytical column. The anticonvulsants are eluted at 60 degrees C with a mobile phase containing acetonitrile:water (21:80 by vol) at a flow rate of 1.0-2.0 ml/min (flow-step gradient). The eluted compounds are monitored at 200 nm. Each analysis requires about 30 min. Analytical recoveries varied from 90 to 98%. Within-day coefficients of variation (CVs) ranged from 0.9 to 4.9%, between-day CVs from 2.8 to 7.6%. The lower limit of detection for all drugs is 0.2 microgram/ml serum, with a sample size of 100 microliters. At therapeutic concentrations we achieved baseline separation for all eight compounds, and there was no interference from other drugs.

Acetonitriles↗
PubMed1985

Effect of phenothiazines on serum antiepileptic drug concentrations in psychiatric patients with seizure disorder.

The intrapatient effect of starting (group A, n = 16), increasing (group B, n = 19), decreasing (group C, n = 23), and discontinuing (group D, n = 34) the phenothiazines (PHZs) thioridazine, chlorpromazine, or mesoridazine on serum phenytoin (PHT), phenobarbital (PB), and primidone (PRI) was studied at a constant antiepileptic drug regimen and between two consecutive steady-state concentration determinations in 92 institutionalized epileptic patients with psychiatric disorders. For PHZ initiation or dosage increase (groups A and B), serum PHT and PHT concentration-to-dose ratio (C/D) decreased by 44 (p less than 0.001) and 41.6% (p less than 0.001) in group A, and 32.9 (p less than 0.001) and 35.3% (p less than 0.005) in group B, respectively. For PHZ dosage decrease or discontinuation (groups C and D), serum PHT and C/D ratio increased by 54.8 (p less than 0.001) and 51.3% (p less than 0.01) in group C, and 71.2 (p less than 0.001) and 69.2% (p less than 0.001) in group D, respectively. The changes for PB were in the same direction, although to a lesser extent. No statistically significant differences were noted for PRI. For groups A and B, the clinical trend was for increase in number of seizures when PHZs were started or dosage increased. For groups C and D, a clear trend for PHT intoxication was evident when PHZ dosages were decreased or discontinued.

Adolescent↗
PubMed1989

Evaluation of assay techniques for the measurement of antiepileptic drugs in serum: a study based on external quality assurance measurements.

The accuracy and precision of eight techniques used to measure a range of eight antiepileptic drugs in human serum were compared using data from 80 samples from the Heathcontrol External Quality Assurance scheme. The fluorescence polarization immunoassay was significantly more precise than other techniques for several analytes, producing the lowest number of measurements rejected as outliers and measurements with the lowest coefficient of variation. Other techniques had a significantly lower precision. Nephelometry (Neph) produced most outliers for phenytoin and carbamazepine and had the highest variability for phenytoin. Gas-liquid chromatography (GLC) with derivatization was most variable for phenobarbitone and primidone. Measurements by GLC with or without derivatization contained greater than 10% of outliers and were least precise for carbamazepine. Differences between the majority of techniques were in many cases, however, not significant. The accuracy of techniques was assessed from differences between sample means and spiked drug concentrations. Neph was notable in producing overestimates at lower concentrations. Immunoassay methods had a 16-21% cross-reactivity with carbamazepine 10,11-epoxide when measuring carbamazepine. All techniques reported underestimates for valproic acid that were thought to result from the hygroscopic nature of the salt used for spiking.

Anticonvulsants↗
PubMed1989

Determination of N-desmethylmethsuximide serum concentrations using enzyme-multiplied and fluorescence polarization immunoassays.

N-Desmethylmethsuximide (NDM), the active metabolite of the antiepileptic agent methsuximide, has been analyzed by gas-liquid chromatography and high-performance liquid chromatography (HPLC) in the past. This study compares methods using two commercially available immunoassays for ethosuximide, the enzyme multiplied immunoassay technique (EMIT) and fluorescence polarization immunoassay (FPIA), with an HPLC method for the measurement of NDM concentrations in serum. Within-day precision studies, utilizing low therapeutic (15.0 mg/L) and toxic (45.0 mg/L) NDM concentrations (n = 20), resulted in coefficients of variation (CVs) of 4.6 and 4.2%, respectively, for EMIT and 5.4 and 3.2%, respectively, for FPIA. Day-to-day precision studies (n = 10) resulted in CVs of 7.6 and 5.5%, respectively, for EMIT and 3.5 and 2.4%, respectively, for FPIA. No interference was observed from toxic concentrations of acetaminophen, caffeine, carbamazepine, methsuximide, phenobarbital, phensuximide, phenytoin, primidone, salicylate, and valproic acid in the EMIT and FPIA procedures. There was good linear correlation between EMIT and HPLC NDM determinations of 50 patient samples (r = 0.970; y = 0.96 x + 0.03), and a similar correlation between FPIA and HPLC NDM determinations in 48 patient samples (r = 0.975; y = 0.91 x + 1.24). Using ethosuximide reagents, both EMIT and FPIA systems can be adapted to reliably measure NDM serum concentrations.

Chromatography, High Pressure Liquid↗
PubMed1994

Improved therapeutic monitoring of drug interactions in epileptic children using carbamazepine polytherapy.

Drug interactions in epileptic children with carbamazepine (CBZ) polytherapy were investigated by analysis of total and free CBZ and its metabolites simultaneously. Heteroinduction effects of CBZ metabolism by other antiepileptic drugs (AEDs), including phenytoin (PHT), phenobarbital (PB), or primidone (PRM), were clearly demonstrated. Serum CBZ level/dose ratios in patients taking CBZ plus other AEDs were decreased while CBZ-10,11-epoxide (CBZ-E) and trans-10,11-dihydroxy-10,11-dihydro-CBZ (CBZ-H) concentrations were significantly increased compared to patients with CBZ alone. Concentration ratios of CBZ-H/CBZ and CBZ-E/CBZ were also significantly higher in patients taking CBZ plus other AEDs. Interactions between CBZ and valproic acid (VPA) involved both protein binding displacement and metabolic inhibition. Patients taking CBZ plus VPA showed significantly increased free fractions of CBZ and CBZ-E and substantially increased serum CBZ-E concentrations and CBZ-E level/dose ratios, while CBZ-H/CBZ-E concentration ratios were decreased compared with patients on CBZ alone. Since this approach investigates the in vivo relationship between substrates and products of the enzymes involved in CBZ biotransformation (the ratios between CBZ and its metabolites), detailed information about the activities of the enzymes may be obtained. This approach appears to be a practical way to improve the monitoring of CBZ metabolism influenced by various physiological or pathological conditions and achieve a better understanding of the drug interactions under different drug regimens (coadministered inhibitor or inducer). This principle may also be adopted for other drugs with similar metabolic characteristics.

Adolescent↗
PubMed1996

A micromethod for the determination of the new antiepileptic drug levetiracetam (ucb LO59) in serum or plasma by high performance liquid chromatography.

An isocratic high performance liquid chromatographic micromethod is described for the quantitation of levetiracetam (ucb L059) in plasma or serum of patients. The chromatography is performed on a 250 x 4 mm I.D. LiChrospher 60 RP-select B, 5-micron column, eluted with an acetonitrile/50 mM phosphate buffer (15:85 vol/vol, pH 5.6) mobile phase, and levetiracetam detected using ultraviolet absorbance at 220 nm. The limit of quantitation was 5 mumol/L and the within-batch and between-batch coefficients of variation were < 7%. No interference from commonly prescribed antiepileptic drugs (carbamazepine and its metabolite carbamazepine epoxide, ethosuximide, gabapentin, lamotrigine, phenobarbitone, phenytoin, primidone, valproic acid, and vigabatrin) was observed, and thus the method can be used to monitor levetiracetam in patients on polytherapy antiepileptic drug regimens.

Anticonvulsants↗
PubMed1996

Stability of therapeutic drug measurement in specimens collected in VACUTAINER plastic blood-collection tubes.

Recently Becton-Dickinson marketed a plastic serum-separator tube that uses the same serum-separator gel as the glass tubes. We studied the stability of therapeutic drugs stored in plastic tubes by comparing it with the stability of drugs stored in glass serum-separator tubes and plain red-top glass tubes. We observed no absorption of caffeine, primidone, N-acetylprocainamide, procainamide, theophylline, tobramycin, ethosuximide, acetaminophen, amikacin, valproic acid, methotrexate, salicylate, and cyclosporine in either plastic or glass serum-separator tubes. On the other hand, concentrations of lidocaine, quinidine, phenobarbital, and phenytoin were reduced after storing in both plastic and glass serum-separator tubes, especially with prolonged storage and small sample volume. The reduction in concentrations were due to slow absorption of those drugs by serum-separator gel.

Blood Specimen Collection↗
PubMed1998

A high-performance liquid chromatography micromethod for the simultaneous determination of vigabatrin and gabapentin in serum.

A gradient high-performance liquid chromatography micromethod is described for the simultaneous quantitation of vigabatrin and gabapentin in human serum. Chromatography was performed using a 125- x 3-mm ID Hypersil BDS C-18 column with a 3-microm mini-bore, eluted with a gradient system comprised of phosphate buffer (pH 6.5)-acetonitrile-methanol-water at a flow rate of 0.45 ml/minute. The column eluent was monitored on a fluorescence detector using excitation and emission wavelengths of 340 and 440 nm, respectively. The lower limit of quantitation for vigabatrin and for gabapentin was 5 micromol/l, and the within-batch and between-batch coefficients of variation were <5%. No interference from commonly prescribed antiepileptic drugs (carbamazepine and its metabolite carbamazepine epoxide, oxcarbazepine and its metabolite 10-hydroxycarbazepine, ethosuximide, lamotrigine, phenobarbitone, phenytoin, primidone, and valproic acid) was observed; thus, the method can be used to monitor vigabatrin and gabapentin in patients on polytherapy antiepileptic drug regimens.

Acetates↗
PubMed1999

Liquid chromatographic determination of six antiepileptic drugs and two metabolites in microsamples of human plasma.

A simple, rapid, sensitive, and reproducible high-performance liquid chromatographic (HPLC) method for simultaneous determination of the antiepileptic drugs (ethosuximide, primidone, lamotrigine, phenobarbital, phenytoin, and carbamazepine) and two metabolites (carbamazepine-diol and carbamazepine-epoxide) in human plasma is described. The procedure involves extraction of the drugs from human plasma (100 microL) with ether using 9-hydroxymethyl-10-carbamyl acridan as an internal standard. The extract was evaporated and reconstituted with mobile phase and then injected onto the chromatograph. The drugs and the internal standard were eluted from a Supelcosil LC-18 stainless steel column at ambient temperature with a mobile phase consisting of a 0.01M phosphate buffer/methanol/acetonitrile (65/18/17, v/v/v) adjusted to a pH of 7.5 with phosphoric acid and a flow rate of 1 mL/min. The effluent was monitored at 220 nm. Quantitation was achieved by using peak area ratio of each drug to the internal standard. The intraassay and interassay coefficients of variation (CV) ranged from 2.43% to 6.25% and from 3.02% to 5.85%, respectively. The absolute (extraction) and relative (analytical) recoveries for the drugs ranged from 70.7% to 104.4% and from 88.3% to 106.1%, respectively. Stability tests showed that the drugs were stable in plasma for at least 4 weeks when stored at -20 degrees C. The method was applied clinically for monitoring the AEDs in epileptic patients.

Anticonvulsants↗
PubMed2002

New antiepileptic drugs: review on drug interactions.

During the Past decade, nine new antiepileptic drugs (AEDs) namely, Felbamate, Gabapentin, Levetiracetam, Lamotrigine, Oxcarbazepine, Tiagabine, Topiramate, Vigabatrin and Zonisamide have been marketed worldwide. The introduction of these drugs increased appreciably the number of therapeutic combinations used in the treatment of epilepsy and with it, the risk of drug interactions. In general, these newer antiepileptic drugs exhibit a lower potential for drug interactions than the classic AEDs, like phenytoin, carbamazepine and valproic acid, mostly because of their pharmacokinetic characteristics. For example, vigabatrin, levetiracetam and gabapentin, exhibit few or no interactions with other AEDs. Felbamate, tiagabine, topiramate and zonisamide are sensitive to induction by known anticonvulsants with inducing effects but are less vulnerable to inhibition by common drug inhibitors. Felbamate, topiramate and oxcarbazepine are mild inducers and may affect the disposition of oral contraceptives with a risk of failure of contraception. These drugs also inhibit CYP2C19 and may affect the disposition of phenytoin. Lamotrigine is eliminated mostly by glucuronidation and is susceptible to inhibition by valproic acid and induction by classic AEDs such as phenytoin, carbamazepine, phenobarbital and primidone.

Animals↗
PubMed2002

Serum concentrations of topiramate in patients with epilepsy: influence of dose, age, and comedication.

Topiramate is a new antiepileptic drug (AED) approved as add-on therapy. Previous studies have shown that topiramate has only a limited effect on other AEDs, but its own metabolism can be induced by enzyme-inducing drugs. The aim of this study was to investigate the influence of topiramate dose, age, and comedication, especially of carbamazepine, phenytoin, phenobarbital, oxcarbazepine, lamotrigine, and valproic acid (VPA) on topiramate serum concentrations in patients with epilepsy. In total, 480 samples of 344 inpatients who fulfilled the inclusion criteria (e.g., trough concentration, body weight available) were investigated. The topiramate serum concentration in relation to topiramate dose per body weight (level-to-dose ratio) was calculated and compared for patients receiving topiramate monotherapy and for patients receiving topiramate plus one other AED. Analysis of covariance (using age as covariate) showed that comedication had a highly significant influence on the topiramate serum concentrations. Regression analysis including all 480 samples confirmed that in combinations with phenytoin, carbamazepine, phenobarbital, and oxcarbazepine, the topiramate concentrations were significantly lower compared with topiramate monotherapy, whereas VPA and lamotrigine had no significant influence. Moreover, regression analysis indicated that primidone and methsuximide lowered topiramate concentrations, whereas gabapentin, bromide, and sulthiame did not. In addition to comedication, the patient's age was significantly correlated with topiramate clearance. In accordance with the results of previous studies, these results indicated that infants and children had lower topiramate concentrations than adults receiving the same topiramate dose per body weight. Comedication and age should be considered in adjusting topiramate dosage. Determination of topiramate serum concentrations may be useful, especially when enzyme-inducing drugs are withdrawn or added.

Adolescent↗
PubMed2004

Fracture risk associated with use of antiepileptic drugs.

PURPOSE: To assess fracture risk associated with different antiepileptic drugs (AEDs). An increased fracture risk has been reported in patients with epilepsy. Classical AEDs have been associated with decreased bone mineral density. The effects of newer AEDs are unknown. METHODS: We undertook a population-based pharmacoepidemiologic case-control study with any fracture as outcome and use of AEDs as exposure variables (124,655 fracture cases and 373,962 controls). RESULTS: All AEDs were associated with an increased fracture risk in an unadjusted analysis. After adjustment for prior fracture, use (ever) of corticosteroids, comorbidity, social variables, and diagnosis of epilepsy, carbamazepine [CBZ; odds ratio (OR), 1.18; 95% confidence interval (CI), 1.10-1.26], [and oxcarbazepine (OXC; 1.14, 1.03-1.26)], clonazepam (CZP; 1.27, 1.15-1.41), phenobarbital (PB; 1.79, 1.64-1.95), and valproate (VPA; 1.15, 1.05-1.26) were statistically significantly associated with risk of any fracture. Ethosuximide (0.75, 0.37-1.52), lamotrigine (1.04, 0.91-1.19), phenytoin (1.20, 1.00-1.43), primidone (1.18, 0.95-1.48), tiagabine (0.75, 0.40-1.41), topiramate (1.39, 0.99-1.96), and vigabatrin (0.93, 0.70-1.22) were not statistically significantly associated with fracture risk after adjustment for confounders. The relative increase was modest and in the same range for the significant and nonsignificant results. CBZ, PB, OXC, and VPA displayed a dose-response relation. Fracture risk was more increased by liver-inducing AEDs (OR, 1.38; 95% CI, 1.31-1.45) than by noninducing AEDs (1.19; 95% CI, 1.11-1.27). CONCLUSIONS: A very limited increased fracture risk is present in users of CBZ, CZP, OXC, PB, and VPA. A limited significant increase cannot be excluded for the other AEDs because of the statistical power.

Adult↗