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Reference ranges for antiepileptic drugs revisited : A practical approach to establish national guidelines

Background and objective: Laboratories sometimes use different reference ranges for the same antiepileptic drug (AED), particularly for new and poorly investigated drugs. This may contribute to misunderstandings, concerns or inappropriate dose changes, which in turn may affect therapeutic effect, drug safety or treatment adherence. Therefore, the Norwegian Association of Clinical Pharmacology wish

No association between non-bullous skin reactions from lamotrigine and heterozygosity of UGT1A4 genetic variants *2(P24T) or *3(L48V) in Norwegian patients

Purpose High initial serum concentrations increase the risk of cutaneous adverse reactions. Genetic variants of the main metabolizing isoenzyme, uridine diphosphate glucuronosyltransferase (UGT) 1A4 influence the elimination of lamotrigine (LTG). Our aim was to investigate the potential association between the two best studied variants, *2 (P24T) and *3 (L48V), and the occurrence non-bullous skin

Pharmacokinetic variability, efficacy and tolerability of eslicarbazepine acetate–A national approach to the evaluation of therapeutic drug monitoring data and clinical outcome

Background Eslicarbazepine acetate (ESL) is a new antiepileptic drug (AED), still insufficiently studied regarding pharmacokinetic variability, efficacy and tolerability. The purpose of this study was to evaluate therapeutic drug monitoring (TDM) data in Norway and relate pharmacokinetic variability to clinical efficacy and tolerability in a long-term clinical setting in patients with refractory e

Hormone replacement therapy with estrogens may reduce lamotrigine serum concentrations : A matched case–control study

Lamotrigine (LTG) is an antiepileptic drug that is metabolized via glucuronidation. Since the glucuronidizing enzyme is inducible by estrogens, LTG serum concentrations may fall by 50–60% when combined with hormonal contraceptives that contain ethinyl estradiol (EE). Little is known about a possible interaction between estrogens used for hormone replacement therapy (HRT) and LTG, and the few avail

The Impact of Pharmacokinetic Interactions with Eslicarbazepine Acetate Versus Oxcarbazepine and Carbamazepine in Clinical Practice

Background: Eslicarbazepine acetate (ESL) is a new anti-epileptic drug (AED) chemically related to oxcarbazepine (OXC) and carbamazepine (CBZ) and is increasingly used in clinical practice. The purpose of the study was to investigate 2-way pharmacokinetic interactions between ESL and other AEDs as compared to OXC and CBZ. Methods: Anonymous data regarding age, gender, use of AEDs, daily doses and

Treatment non-adherence in pseudo-refractory epilepsy

Non-adherence to antiepileptic drug treatment strongly affects the outcome of epilepsy and is frequently clinically unrecognized. This review addresses current knowledge on medication-taking behavior in people with epilepsy, as well as the importance of tailoring interventions to the individual patterns of non-adherence.Non-adherence can be categorized as non-initiation, poor execution (accidental

Frequencies of UGT1A4∗2 (P24T) and∗3 (L48V) and their effects on serum concentrations of lamotrigine

The gene encoding uridine diphosphate glucuronosyltransferase (UGT) 1A4 shows considerable polymorphism. Several common drugs are metabolised by UGT1A4, among them lamotrigine (LTG). Experimental and clinical studies suggest that certain variants of UGT1A4 are associated with altered enzyme activity. However, results are conflicting. This clinical study aimed to investigate the frequencies of two

Interactions between hormonal contraception and antiepileptic drugs : Clinical and mechanistic considerations

Antiepileptic drugs (AEDs) and hormonal contraceptives may affect each other's metabolism and clinical efficacy. Loss of seizure control and unplanned pregnancy may occur when these compounds are used concomitantly. Although a large number of available preparations yield a plethora of possible drug combinations, most of these drug interactions are predictable and, thus, avoidable. Unfortunately, t

New antiepileptic drugs and women

Since 1990, sixteen new antiepileptic drugs (AEDs) have been introduced. Most of these new AEDs have only been insufficiently studied with respect to women-specific aspects such as endogenous sex hormones, hormonal contraception, pregnancy, breastfeeding, or menopause. This is of concern because it has been shown for some of the new AEDs that these factors may have a clinically significant impact

Is dietary caffeine involved in seizure precipitation?

Caffeine acts as a central nervous stimulant by blocking A1 and A2A adenosine receptors. Its effect on seizures is complex. Animal studies and case reports indicate that acute caffeine exposure may induce seizures, whereas chronic exposure might have an opposite effect. Patients acutely hospitalized for seizures (n=174) were asked for their consumption of caffeinated beverages 24. h prior to admis

Relating fatty acid composition in human fingertip blood to age, gender, nationality and n-3 supplementation in the Scandinavian population

This study investigated data obtained from whole blood fatty acid (FA) composition of 3476 Norwegian and Swedish individuals, which provided background information including age, gender, nationality and self-motivated n-3 supplement consumption. The aim of this paper was to statistically relate this background information on the subjects to their whole blood FA profile, focusing mainly on the n-3

Second-generation antiepileptic drugs and pregnancy : A guide for clinicians

When treating pregnant women with antiepileptic drugs (AEDs), clinicians have to balance potential fetal adverse effects against the risks of uncontrolled maternal disease. Only recently have emerging scientic data provided a rational basis for treatment decisions considering both aspects. The focus of research is currently moving from the first to the second AED generation. Lamotrigine is relativ

Benzoylated uronic acid building blocks and synthesis of n-uronate conjugates of lamotrigine

A chemoenzymatic approach towards benzoylated uronic acid building blocks has been investigated starting with benzoylated hexapyranosides using regioselective C-6 enzymatic hydrolysis as the key step. Two of the building blocks were reacted with the antiepileptic drug lamotrigine. Glucuronidation of lamotrigine using methyl (2,3,4-tri-O-benzoyl-a-D-glycopyranosyl bromide)uronate proceeded to give

Lamotrigine and its N2-glucuronide during pregnancy : The significance of renal clearance and estradiol

Purpose: To investigate the physiological mechanisms behind the pronounced decline of lamotrigine (LTG) serum concentrations during pregnancy. Methods: Serum and urine concentrations of LTG and its main metabolite, LTG-N2-glucuronide (LTG-GLUC), were measured monthly in 21 pregnancies of 19 women using LTG. Simultaneously, a panel of biochemical variables was monitored to evaluate liver and kidney

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Bakgrunn.I 2007 kom det anbefalinger om at serumkonsentrasjonen av digitoksin bør ligge i området 8 – 15 nmol/l, noe som er ca. halvparten av det som tidligere var ansett som optimalt, og forslag til nye doseringsrutiner.Materiale og metode.Utviklingen for angitt dosering og serumkonsentrasjoner av digitoksin er undersøkt med utgangspunkt i 13 054 prøver sendt til Avdeling for klinisk farmakologi