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Perspective: multi-configurational methods in bio-inorganic chemistry

Transition metal ions play crucial roles in the structure and function of numerous proteins, contributing to essential biological processes such as catalysis, electron transfer, and oxygen binding. However, accurately modeling the electronic structure and properties of metalloproteins poses significant challenges due to the complex nature of their electronic configurations and strong correlation e

Allt fler kvinnor i fertil ålder tar antidepressiva läkemedel

Depression is common during pregnancy, and a considerable proportion of pregnant women take antidepressants. Modern antidepressants (e.g. SSRIs) are fairly safe to use during pregnancy. Several physiological changes occur in the pregnant state, possibly affecting the pharmacokinetics of many drugs. Metabolism via CYP enzymes are important for the elimination of antidepressants. This metabolism mayDepression is common during pregnancy, and a considerable proportion of pregnant women take antidepressants. Modern antidepressants (e.g. SSRIs) are fairly safe to use during pregnancy. Several physiological changes occur in the pregnant state, possibly affecting the pharmacokinetics of many drugs. Metabolism via CYP enzymes are important for the elimination of antidepressants. This metabolism may

Zonisamide serum concentrations during pregnancy

Purpose: To investigate the change in zonisamide (ZNS) serum concentration and its consequences in pregnant women with epilepsy. Methods: Six hospitals in Norway and Denmark screened their records for women who had been using ZNS during pregnancy. Absolute serum concentrations as well as concentration/dose (CD)-ratios were compared to non-pregnant values. Descriptive data on seizure control and ob

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