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Torbjörn Tomson

Publications and source records attributed to Torbjörn Tomson.

31 records · Page 2Linked to original sources
PubMed2003

[Antiepileptic treatment nearly six times more expensive since 1990].

There is a six-fold increase in the costs for antiepileptic drug prescriptions in Sweden from 1990 to 2000. This is mainly caused by a gradual increase in the prescribing of new and more expensive drugs, since the total use of antiepileptic drugs, expressed as defined daily doses per 1,000 inhabitants, is almost unchanged during the same time period. A marked variation in the prescribing of new antiepileptic drugs between different counties in Sweden, suggests that the role of the new compounds is still unclear. The cost effectiveness of new antiepileptic drugs in relation to the older drugs requires further evaluation.

Anticonvulsants↗
PubMed2003

Carbamazepine affects autonomic cardiac control in patients with newly diagnosed epilepsy.

Previous studies indicate that epilepsy patients may have impaired autonomic cardiovascular control in the interictal state although it is unclear whether the observed reduction in cardiovascular responses is due to the epilepsy and the interictal epileptogenic discharges, or to the treatment with antiepileptic drugs. Spectral analysis of heart rate variability makes it possible to partly separate the sympathetic components, low frequency (LF), from the vagal components, high frequency (HF) of autonomic cardiac control. We used spectral analysis of heart rate variability to assess the effect of carbamazepine (CBZ) on autonomic cardiac control in patients with newly diagnosed epilepsy. Fifteen adult outpatients with newly diagnosed seizures/epilepsy underwent 24 h ambulatory EKG recordings before and after commencement of CBZ treatment. Total power as well as low frequency (LF), very low frequency (VLF) and high frequency (HF) power in heart rate variability was calculated. When analysing the full 24 h recordings, patients had significantly lower standard deviation of RR-intervals (P=0.0015), total power (P=0.0010), LF (P=0.0002), VLF (P=0.0025) and HF (P=0.0139) during treatment with CBZ than before. The results were very similar for daytime and night time recordings. Our observations demonstrate that CBZ may suppress both parasympathetic and sympathetic functions in newly diagnosed patients with epilepsy. The possible implications of our results for sudden unexpected death in epilepsy are discussed.

Adult↗
PubMed2003

Therapeutic drug monitoring of the newer antiepileptic drugs.

The aim of the present review is to discuss the potential value of therapeutic drug monitoring (TDM) of the newer antiepileptic drugs (AEDs) felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin, and zonisamide. Studies of the relationship between serum concentrations and clinical efficacy of these drugs are reviewed, and the potential value of TDM of the drugs is discussed based on their pharmacokinetic properties and mode of action. Analytical methods for the determination of the serum concentrations of these drugs are also briefly described. There are only some prospective data on the serum concentration-effect relationships, and few studies have been designed primarily to study these relationships. As TDM is not widely practiced for the newer AEDs, there are no generally accepted target ranges for any of these drugs, and for most a wide range in serum concentration is associated with clinical efficacy. Furthermore, a considerable overlap in drug concentrations related to toxicity and nonresponse is reported. Nevertheless, the current tentative target ranges for felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine (10-hydroxy-carbazepine metabolite), tiagabine, topiramate, vigabatrin, and zonisamide are 125 to 250 micromol/L, 70 to 120 micromol/L, 10 to 60 micromol/L, 35 to 120 micromol/L, 50 to 140 micomol/L, 50 to 250 nmol/L, 15 to 60 micromol/L, 6 to 278 micromol/L, and 45 to 180 micromol/L, respectively. Further systematic studies designed specifically to evaluate concentration-effect relationships of the new AEDs are urgently needed. Although routine monitoring in general cannot be recommended at present, measurements of some of the drugs is undoubtedly of help with individualization of treatment in selected cases in a particular clinical setting.

Anticonvulsants↗
PubMed2003

Unbound valproate fraction in plasma and subcutaneous microdialysate in steady state and after a single dose in humans.

The aim of the current study was to characterize the observed discrepancy between unbound plasma valproate (VPA) in single dose and steady state in humans. Unbound and total plasma VPA and subcutaneous microdialysate VPA concentrations were estimated in single dose (6 subjects, n = 33) and steady state (11 subjects, n = 110). Trough plasma samples from 14 patients with total VPA concentrations of 300 micromol/L and 14 patients with VPA concentrations ranging from 600 to 700 micromol/L were analyzed for the unbound VPA fraction and compared with the unbound VPA fraction in spiked plasma samples from healthy subjects containing similar total VPA concentrations. The unbound plasma VPA fraction was significantly higher (P < 0.001) in the steady-state group compared with the single-dose group. The unbound VPA fraction was significantly higher in steady state compared with spiked plasma samples at high and low total VPA concentrations (P < 0.001). The difference between microdialysate and unbound plasma VPA concentrations was significant in the steady-state group (P < 0.001), while no difference was observed in the single-dose group. The mean (+/- SD) subcutaneous microdialysate-to-unbound plasma ratio in the single-dose and steady-state groups was 1.08 (+/- 0.401) and 0.74 (+/- 0.123), respectively. The ratio difference between the groups was significant (P < 0.001). The results of the current study show that unbound plasma fractions of VPA are consistently higher in steady state compared with single dose. Together with the finding of higher unbound VPA fraction in steady state compared with spiked plasma samples, these results provide indirect evidence of displacement of VPA from plasma proteins by product(s) of VPA biotransformation. In addition, subcutaneous microdialysate VPA levels were consistently lower than unbound plasma levels in steady state but not after single dose. The mechanisms underlying this observation need to be studied further.

Adult↗
PubMed2003

Serum concentrations and effects of gabapentin and vigabatrin: observations from a dose titration study.

To explore possible concentration-effect relationships, gabapentin (GBP) and vigabatrin (VGB) serum concentrations were obtained from patients participating in an add-on dose-titration trial comparing GBP and VGB in partial epilepsy. Patients randomized to GBP started on 1800 mg/d and could have their dosage increased stepwise to 2400 and 3600 mg/d if seizures persisted. Those randomised to VGB started on 1000 mg/d, and the dose could be increased to 2000 and 4000 mg/d. Blood samples were obtained at steady state, at a nonstandardized time, from 27 patients randomized to GBP and from 36 randomized to VGB. Serum samples were analyzed using high-performance liquid chromatography. The treatment effect was expressed as percentage reduction in number of seizures from baseline. In addition, patients were classified as responders (>50% reduction in number of seizures from baseline) or nonresponders. There was no significant correlation between serum concentrations of GBP and seizure reduction at the lowest dosage, 1800 mg/d (r = -0.02, P = 0.94, Spearman-rank), nor between VGB serum levels and seizure reduction at 1000 mg/d of VGB (r = -0.14, P = 0.44). The serum GBP concentrations among responders to GBP 1800 mg/d were 26 +/- 12 micro mol/L (mean +/- SD), which was not different from serum concentrations in nonresponders, 28+/-13 micro mol/L. Nor was there a difference between serum concentrations of responders and nonresponders to VGB 1000 mg/d (32 +/- 23 and 44 +/- 36 micro mol/L, respectively). Hence, with the present study design we were unable to identify specific target ranges of GBP and VGB serum concentrations.

Acetates↗
PubMed2002

[Epilepsy surgery--a superior but underutilized method. Results of an evidence-based Canadian study].

Wiebe and collaborators have conducted a clinical trial in which patients with temporal lobe epilepsy were randomly assigned to surgery or to continued treatment with antiepileptic drugs. At follow-up after one year, 38 percent of patients in the surgery group were completely seizure free compared with 3 percent among the medically treated control patients. The study demonstrates superiority of surgery in the short one-year perspective for selected patients. Swedish register data indicate that epilepsy surgery is underutilized and that patients are referred to assessment for surgery only after several years delay.

Canada↗
PubMed2002

Microdialysis sampling of carbamazepine, phenytoin and phenobarbital in subcutaneous extracellular fluid and subdural cerebrospinal fluid in humans: an in vitro and in vivo study of adsorption to the sampling device.

The purpose of the study was to determine if binding of the drugs to the sampling equipment during microdialysis would influence the results for carbamazepine, phenytoin and phenobarbital. In vitro experiments with microdialysis catheters and separate parts of catheters were performed to estimate the degree of drug binding to the dialysis equipment. A mathematical model to calculate drug binding and recovery is proposed. In vivo protein unbound carbamazepine concentrations in subcutaneous extracellular fluid at different flow rates (6 patients), unbound carbamazepine (1 patient) and unbound phenobarbital (I patient) in subdural cerebrospinal fluid and subcutaneous extracellular fluid were estimated and the in vivo data were compared to the in vitro results and data generated by the mathematical model. Binding to the soft outlet polyurethane tubing was extensive and variable for phenytoin, which precluded in vivo testing, but limited and more predictable for carbamazepine and phenobarbital. None of the three compounds bound to the hard internaltubing. Phenytoin and phenobarbital did not bind to the dialysis membrane, while a small degree of binding may be present for carbamazepine. In vivo estimates of carbamazepine protein unbound subcutaneous extracellular concentrations by microdialysis, adjusted for binding to the plastic tubing, were 81% of protein unbound plasma concentrations. In single case studies, subdural cerebrospinal fluid and subcutaneous extracellular levels of carbamazepine and phenobarbital were similar and when corrected for binding to the plastic tubings they were also close to protein unbound plasma concentrations. Microdialysis can be used for reliable estimations of protein unbound carbamazepine and possibly phenobarbital concentrations when drug binding to the plastic tubing is considered. Reliable estimation of unbound phenytoin is not possible at present.

Adult↗
PubMed2002

Topiramate kinetics during delivery, lactation, and in the neonate: preliminary observations.

PURPOSE: To study the pharmacokinetics of topiramate (TPM) during delivery, lactation, and in the neonate. METHODS: TPM concentrations in plasma and breast milk were measured with fluorescence polarization immunoassay (FPIA) in five women with epilepsy treated with TPM during pregnancy and lactation. Blood samples were obtained at delivery from mothers, from the umbilical cord, and from the newborns on three occasions (24, 48, and 72 h) after delivery. Blood and breast milk also were collected from mothers 2 weeks, and 1 and 3 months postpartum. Blood samples also were drawn from the infants during breast-feeding. Three of the mother-infant pairs were studied both at delivery and during lactation; two contributed with data from delivery only. RESULTS: The umbilical cord plasma/maternal plasma ratios were close to unity, suggesting extensive transplacental transfer of TPM. The mean milk/maternal plasma concentration ratio was 0.86 (range, 0.67-1.1) at 2-3 weeks after delivery. The milk/maternal plasma concentration ratios at sampling 1 and 3 months after delivery were similar (0.86 and 0.69, respectively). Two to 3 weeks after delivery, two of the breast-fed infants had detectable (>0.9 microM) concentrations of TPM, although below the limit of quantification (2.8 microM), and one had an undetectable concentration. CONCLUSIONS: Our limited data suggest free passage of TPM over the placenta and an extensive transfer into breast milk. Breast-fed infants had very low TPM concentrations, and no adverse effects were observed in the infants.

Anticonvulsants↗
PubMed2002

Risk factors for suicide in epilepsy: a case control study.

PURPOSE: Suicide is considered to be one of the most important causes of death contributing to the increased mortality of persons with epilepsy. We investigated the association between the risk of suicide in persons with epilepsy and clinical factors that might increase or have been suggested to increase the risk of suicide. METHODS: A case-control study was nested within a cohort of 6,880 patients registered in the Stockholm County In-Patient Register with a diagnosis of epilepsy. The study population was followed up through the National Cause of Death Register. Twenty-six cases of suicide, 23 cases of suspected but not proven suicide, and 171 controls, living epilepsy patients, were selected from the cohort. Clinical data were collected through medical record review. RESULTS: There was a ninefold increase in risk of suicide with mental illness and a 10-fold increase in relative risk (RR) with the use of antipsychotic drugs. The estimated RR of suicide was 16.0 [95% confidence interval (CI), 4.4-58.3] for onset of epilepsy at younger than 18 years, compared with onset after 29 years. The risk of suicide seemed to increase with high seizure frequency and antiepileptic drug (AED) polytherapy, although the estimates were imprecise and the associations not statistically significant. Insufficient data on seizure frequency and changes in AED dosage due to incomplete case records were associated with high RRs. We found no association between risk of suicide and any particular AED, with type of epilepsy, or localization or lateralization of epileptogenic focus on EEG [RR = 0.3 (95% CI, 0.1-1.7)]. CONCLUSIONS: The profile of the epilepsy patient who commits suicide that emerges from our study is a patient with early onset (particularly onset during adolescence) but not necessarily severe epilepsy, psychiatric illness, and perhaps inadequate neurologic follow-up. Previous reports of an association with temporal lobe epilepsy could not be confirmed.

Adolescent↗
PubMed2001

To the Editor.

Explore the source record for details and available documents.

Journal Article↗
PubMedDate not supplied

Progress report on new antiepileptic drugs: a summary of the Seventh Eilat Conference (EILAT VII).

The Seventh Eilat Conference on New Antiepileptic Drugs (AEDs) (EILAT VII) took place in Villasimius, Sardinia, Italy from the 9th to 13th May 2004. Basic scientists, clinical pharmacologists and neurologists from 24 countries attended the conference,whose main themes included advances in pathophysiology of drug resistance, new AEDs in pediatric epilepsy syndromes, modes of AED action and spectrum of adverse effects and a re-appraisal of comparative responses to AED combinations. Consistent with previous formats of this conference, the central part of the conference was devoted to a review of AEDs in development, as well as updates on second-generation AEDs. This article summarizes the information presented on drugs in development, including atipamezole, BIA-2-093, fluorofelbamate, NPS 1776, pregabalin, retigabine, safinamide, SPM 927, stiripentol, talampanel,ucb 34714 and valrocemide (TV 1901). Updates on felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine,topiramate, vigabatrin, zonisamide, new oral and parenteral formulations of valproic acid and SPM 927 and the antiepileptic vagal stimulator device are also presented.

Adult↗
PubMedDate not supplied

Phenytoin and phenobarbital inhibit human HERG potassium channels.

Drugs that inhibit the cardiac rapid delayed rectifier potassium ion current (IKr) channel can be proarrhythmic and their clinical use has been associated with sudden unexpected death (SUD). Since SUD is about 20 times more common among people with epilepsy than in the general population, and some data indicate that drug treatment may contribute, we tested the hypothesis that the classic antiepileptic drugs phenytoin (PHT), carbamazepine (CBZ), and phenobarbital (PB) have a potential to block IKr. The whole cell patch-clamp recording technique was used to study the effects on IKr channels expressed by the human ether-a-go-go related gene (HERG) stably expressed in Human Embryo Kidney (HEK) 293 cells. Tail currents, which are purely related to HERG, were blocked with an IC50 (the concentration when 50% inhibition was obtained compared to control values) of 240 microM for PHT and 3 mM for PB. A 20% inhibition of tail currents was obtained at CBZ concentrations of 250 and 500 microM. Collective data show that drugs with the same margins (ratio HERG IC50/unbound therapeutic concentration), as PHT and PB, may have arrhythmogenic potential, especially when used in predisposed patients and in the case of drug-drug interactions. SUD in epilepsy is generally a seizure-related phenomenon. However, our data suggest that PHT and PB may play a contributing role, perhaps by making some patients more vulnerable to the cardiovascular depression induced by seizures.

Cation Transport Proteins↗