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Introduction
Arne Reimers currently is the head of Clinical Pharmacology at the Department of Clinical Chemistry and Pharmacology, Lund University Hospital, Sweden. Arne has a special interest in clinical neuropsychopharmacology, cognitive adverse drug effects, pharmacogenomics incl. pharmacological epigenetics, and (endo)cannabinoids.
Current institution
Additional affiliations
August 2018 - present
August 2002 - August 2006
Publications
Publications (70)
Antiepileptic drugs (AEDs) are effective against seizures, but their use is often limited by adverse effects, among them psychiatric and behavioral ones including aggressive behavior (AB). Knowledge of the incidence, risk factors, and the underlying mechanisms of AB induced by AEDs may help to facilitate management and reduce the risk of such side...
Choosing appropriate medication doses for pregnant women is a difficult balancing act, as the mother's need for treatment must be weighed against the risk of fetal harm. The latter is frequently considered to be the most pressing concern, with the result that drugs are discontinued or doses reduced. It is perhaps less well known that pregnant women...
The number of reports on suspected drug-induced memory impairment submitted to the US Food and Drug Administration increased 30-fold from 2000 to 2022. Drugs are the most common cause of reversible dementia. However, there is very little research on drug-induced cognitive impairment. The aim of this study was to investigate if and how an assessment...
Drug-induced cognitive impairment (DICI) is a well-established, yet under-recognised, complication of many types of pharmacological treatment. While there is a large body of scientific literature on DICI, most papers are about drug-induced dementia in the elderly and one specific drug class. However, DICI also comprises subclinical symptoms, domain...
Många människor använder läkemedel och många läkemedel påverkar hjärnans funktion. Det är därför viktig att neuropsykologen vet hur läkemedel utövar sina effekter och hur dessa kan påverka utfall av neuropsykologiska tester. Detta kapitel ger en introduktion i grundläggande farmakologi samt hur neuro- och psykofarmaka och andra läkemedel påverkar h...
Purpose; Cutaneous adverse drug reactions (cADRs) are a major cause of lamotrigine (LTG) discontinuation. Remarkable variation in their reported incidence suggests confounders and diverse terms and definitions. The aim of this study was to identify immunological cADRs and to throw light on classification and differential diagnoses in children and a...
Purpose
To explore associations between the characteristics of people with epilepsy (PWE) and their attitudes toward generic substitution of antiseizure drugs (ASDs) in epilepsy.
Methods
This was a cross-sectional survey study directed at adults with epilepsy using selected brand drugs: Keppra®, Lamictal®, Lyrica® or Topimax®. Symptoms of anxiety...
Antiepileptic drugs (AEDs) are used to treat epilepsy, i.e., the repeated occurrence of unprovoked epileptic seizures. They are also used in other conditions, e.g., bipolar disorder, neuropathic pain, or migraine. None of the available AEDs does cure epilepsy. Instead, they suppress epileptic discharges in the brain, thereby reducing seizure freque...
HUVUDBUDSKAP:
Depression är vanligt förekommande vid graviditet.
Risken för fosterskador är liten med de flesta antidepressiva läkemedel.
Fysiologiska förändringar i samband med graviditet påverkar läkemedels farmakokinetik.
Metabolism via CYP har stor betydelse för eliminationen av antidepressiva läkemedel.
CYP-aktiviteten kan förändras vid gravid...
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 e...
BACKGROUND:
Improved quality of life (QoL) is one of the most important objectives in the treatment of epilepsy. Recent prospective, clinical studies proved no significant differences between brand antiepileptic drugs (AEDs) and their generic equivalents in terms of seizure control, pharmacokinetics, or safety. In this study, we focused on possible...
The prevalence of neurologic and psychiatric diseases has been increasing for decades and, given the moderate therapeutic efficacy and safety profile of existing pharmacological treatments, there is an urgent need for new therapeutic approaches. Nutrition has recently been recognized as an important factor for the prevention and treatment of neurop...
Introduction: About 70 million people worldwide are estimated to suffer from epilepsy. Despite a large variety of old and new antiepileptic drugs on the market, about 30% of people with epilepsy do not become seizure-free with medical treatment. This is a major individual and public health burden. Most of these difficult-to-treat patients are havin...
Lamotrigine (LTG) was introduced in 1991 as one of the first second‐generation antiepileptic drugs, and very soon its mood‐stabilizing effects were discovered. Today, LTG is one of the most used drugs for epilepsy and mood disorders, especially in women. Because it is devoid of enzyme‐inducing properties, LTG does not affect the efficacy of hormona...
Choosing appropriate medication doses for pregnant women is a difficult balancing act, as the mother’s need for treatment must be weighed against the risk of fetal harm. The latter is frequently considered to be the most pressing concern, with the result that drugs are discontinued or doses reduced. It is perhaps less well known that pregnant women...
Choosing appropriate medication doses for pregnant women is a difficult balancing act, as the mother’s need for treatment must be weighed against the risk of fetal harm. The latter is frequently considered to be the most pressing concern, with the result that drugs are discontinued or doses reduced. It is perhaps less well known that pregnant women...
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-pregna...
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 No...
Background:
Switching patients from a branded antiepileptic drug (AED) to a generic is often challenging. Several studies have shown that considerable proportions of patients report deteriorated seizure control or increased adverse effects, enforcing a switchback to the original drug. Since tolerability and seizure control usually correlate with A...
Antiepileptic drugs are the cornerstone of epilepsy treatment and are also used in a range of other indications. Measurement of the serum concentrations of antiepileptic drugs has a long tradition as a tool in the treatment of epilepsy in Norway. New and updated national reference ranges for serum concentration measurements of antiepileptic drugs i...
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...
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)...
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 re...
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...
Approximately 50% of all pregnancies in women with epilepsy (WWE) occur unplanned. This is worrying, given the increased occurrence of obstetrical complications in WWE, including the risk of seizures and their possible consequences for both the mother and the unborn child. Hormonal contraception is usually regarded as highly effective, but it is su...
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 catego...
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...
The aim was to assess the clinical relevance of antiepileptic drug (AED) nonadherence by means of therapeutic drug concentration monitoring (TDM). Two hundred eighty-two consecutive patients with epilepsy acutely admitted to hospital for seizures were included. Nonadherence was defined as having a serum concentration/dose ratio at admission of <75%...
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...
Since 1990, sixteen new antiepileptic drugs (AEDs) have been introduced. Most of these new AEDs are only insufficiently studied with respect to women-specific aspects such as endogenous sex hormones, hormonal contraception, pregnancy, breastfeeding, or menopause. This is concerning, because it has been shown for some of the new AEDs that these issu...
The aim was to assess the clinical relevance of antiepileptic drug (AED) nonadherence by means of therapeutic drug concentration monitoring (TDM). Two hundred eighty-two consecutive patients with epilepsy acutely admitted to hospital for seizures were included. Nonadherence was defined as having a serum concentration/dose ratio at admission of <75%...
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 consump...
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...
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 w...
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-α-d...
In Norway several hundred thousand urine samples are analysed annually to reveal substance abuse. Our laboratory analyses substances with a potential of abuse in about 60,000 urine specimens annually. We wished to find out if our standard panel of analyses can detect most of these substances.
In summer 2009, our department analysed ten substances t...
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...
The placenta contains a large variety of metabolizing enzymes, among them UDP-glucuronosyltransferase (UGT). Several UGT2B isozymes have so far been detected in human placenta, but little is known on placental expression of UGT1A isozymes. The antiepileptic drug lamotrigine (LTG) is a UGT1A4-substrate, and its serum concentration falls by over 50%...
In 2007, new Norwegian guidelines suggested that serum concentrations of digitoxin should be in the interval 8 - 15 nmol/l, which is about 50 % lower than previous recommendations.
We studied trends in dosing and serum concentrations of digitoxin in the period 2000 - 08, based on 13 054 serum samples sent to our laboratory for analysis in that peri...
Both Carl Friedrich von Weizsäcker und Max Born belong to the most active scientists, which have raised their voice for peace in the 1950s. While Born, senior to Weizsäcker by one generation, engaged in peace movements at an early stage, which was also due to his emigration, and was a driving force for the Einstein-Russell memorandum, Weizsäcker en...
To investigate long-term trends and changes in the pattern of use of lamotrigine (LTG).
Retrospective survey of a large, routine therapeutic drug monitoring database.
Twelve thousand one hundred and seven samples from 4123 subjects were analysed from October 1999 to May 2007. Within this period, the mean daily dose rose from 183 to 253 mg, whereas...
To study the impact of pregnancy on the serum concentration/dose ratio (C/D-ratio) of topiramate (TPM).
Twelve women with epilepsy using TPM during pregnancy, and 15 pregnancies were studied. The main target variable was the C/D-ratio at baseline and during pregnancy. Additional variables were changes in TPM dose, concomitant use of other antiepile...
The main concerns associated with epilepsy during pregnancy consist of maternal and fetal risks from uncontrolled seizures, and harmful effects of the treatment on the development of the offspring. Although seizure control is maintained in the majority, worsening occurs in a fraction of childbearing women with epilepsy. As multiple factors associat...
![Figure 2 Individual serum concentration/dose ratios [(mmol/L)/(mg/day)]...](profile/Arne-Reimers/publication/5670532/figure/fig2/AS:339892631556100@1458048126497/ndividual-serum-concentration-dose-ratios-mmol-L-mg-day-at-baseline-and-during-the_Q320.jpg)
![Serum concentration/dose ratio [(mmol/L)/(mg/day)] of levetiracetam...](profile/Arne-Reimers/publication/5670532/figure/tbl3/AS:780907489280002@1563194262517/Serum-concentration-dose-ratio-mmol-L-mg-day-of-levetiracetam-during-and-after_Q320.jpg)
To investigate changes in levetiracetam (LEV) serum concentration/dose ratio (C/D-ratio) in relation to pregnancy.
Altogether 21 consecutive pregnancies in 20 women with epilepsy receiving LEV during gestation were studied retrospectively. The main target variable was the C/D-ratio before and during pregnancy, and in the post partum period. Seconda...
In some situations, and particularly when intoxications are suspected, it would be advantageous if medicines and drugs of abuse could be swiftly detected in serum or urine.
The Department of Clinical Pharmacology at St. Olav University Hospital has since 2004 been developing a comprehensive toxicology service (at all hours 7-days/week) for immediat...
To investigate the impact of age and co-treatment with other drugs on the serum concentrations of lamotrigine in children and adolescents.
A review of routine serum concentration measurements of lamotrigine performed in our laboratory yielded a total of 744 serum samples from 296 subjects (110 males, 186 females, age: 2-19 years) suitable for stati...
To measure the serum concentrations of lamotrigine throughout a complete menstrual cycle.
Serum concentrations of lamotrigine, estradiol, and progestogen throughout a menstrual cycle were measured in 2 young women not using hormonal contraception.
The physiological hormonal fluctuations during an ovulatory cycle were not associated with clinically...
Efficient prevention of adverse drug reactions (ADRs) requires knowledge about their severity and pharmacological mechanisms and is dependent on reliable data on their frequencies and possible risk factors. The study was conducted to investigate the prescribers' experience and understanding of the ADRs of psychotropic drugs, and their attitude towa...
To study the interaction between lamotrigine (LTG) and hormonal contraception.
LTG serum concentrations of female patients using either no hormonal contraception (n=18), an ethinyl estradiol (EE)-containing (n=11), or a progestogen (PG)-only-containing compound (n=16) were analyzed. Patients were recruited prospectively, and blood samples were draw...
We present a systematic study on the interaction potential of lamotrigine, with focus on psychoactive drugs. A review of routine serum concentration measurements of lamotrigine performed in our laboratory yielded a total of 1733 serum samples from 829 patients (530 women, 299 men) suitable for statistical analysis. Main results for the whole study...
We present a systematic study on the interaction potential of lamotrigine, with focus on psychoactive drugs. A review of routine serum concentration measurements of lamotrigine performed in our laboratory yielded a total of 1733 serum samples from 829 patients (530 women, 299 men) suitable for statistical analysis. Main results for the whole study...
The effects of myoglobin on renal microcirculation were studied in anesthetized rats subjected to hemorrhagic hypotension. Capillary flow distribution was determined by allowing two dyes to circulate for 3 and 1 min, respectively, freezing the left kidney and quantifying the dye distribution in histological sections by analyzing the distances of re...
The effects of the medicinal plant rue (Ruta graveolens L.) on MS-related visual-field defects was tested. In five of nine patients the scotomata were reduced by a single dose of an aqueous extract of 3 g of the drug; the effect was reversible, appearing after only about two hours and lasting for one to two days. There was no detectable action in f...
Questions
Questions (3)
What is the therapeutic index (LD50/ED50 of oxycodone)? Preferably in humans but any number with a reference would be welcome. I am preparing a lecture for medical students on opioid pharmacology and I am suprised that I cannot find anything on the net. Even for other opioids it is surprisingly hard to find any data.
Viruses, per definition, are not alive as they don't have a metabolism. How then do they attach to a cell, make a hole into the cell membrane, inject their DNA into this cell, make it travel through the cell to the nucleus, enter the nucleus and splice it into the host DNA? These steps, or at least the first two of it, apparently require energy that has to come from the virus. Where does this energy come from, without any metabolism?
When developing population pharmacokinetic models, body weight and age are usually tested separately as covariates, implying that they are independent. However: in children, age and body weight are strongly correlated. Higher age means higher body weight. Is it indeed possible to treat these two variables as if they were separate when developing POP-PK models for children? If so, how?
