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O Spigset

Publications and source records attributed to O Spigset.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Drugs in practice].

Explore the source record for details and available documents.

Drug Information Services↗
PubMed2000

Association of venous thromboembolism and clozapine.

Data from the Swedish Adverse Reactions Advisory Committee suggest that use of clozapine is associated with venous thromboembolic complications. We summarise 12 cases of thromboembolism during clozapine treatment. In five cases the outcome was fatal.

Adult↗
PubMed2000

[From ready-made to tailor-made--future possibilities for individualized drug therapy].

Knowledge of the genetic code offers great promise for individualised drug therapy. Recent advances in molecular biology and biotechnology have led to new possibilities in the prediction of therapeutic effects and risks of adverse reactions based upon the patient's individual genotype. In addition, these techniques are the basis of gene therapy and are a prerequisite for the development of many other new drugs. This article presents the current status in these fields and discusses to which extent the present promises can be expected to be realised in the future.

Drug Therapy, Computer-Assisted↗
PubMed2000

Citalopram pharmacokinetics in patients with chronic renal failure and the effect of haemodialysis.

OBJECTIVE: To study the effects of severe renal failure and haemodialysis on the pharmacokinetics of citalopram. METHODS: Four patients with renal failure undergoing haemodialysis and eight healthy controls were given a single dose of citalopram. The concentrations of citalopram and its metabolites desmethylcitalopram and didesmethylcitalopram were measured in serum and urine. On a different day, the four patients undergoing haemodialysis were given another single dose of citalopram, and the drug concentrations were measured in serum from the artery leading to the dialyser and in the dialysate. In addition, one anuric patient treated with citalopram on a regular basis was included in the study. RESULTS: There were no significant differences between the two groups in any of the pharmacokinetic parameters with the exception of the renal clearance of citalopram, which was significantly lower in the renal failure group than in the control group (1.70 ml/min versus 66.2 ml/min, P<0.001). Oral clearance of citalopram was almost identical in the two groups (452 ml/min versus 456 ml/min). The process of haemodialysis cleared about 1% of the dose as citalopram and 1% as desmethylcitalopram only. CONCLUSION: Severe renal failure does not affect the pharmacokinetics of citalopram and modification of the usual citalopram dose does thus not seem to be necessary. The contribution of haemodialysis to the total elimination of citalopram is negligible.

Adult↗
PubMed2000

Serotonin 5-HT2A receptor binding in platelets from patients with Alzheimer's disease or vascular dementia.

It is well known that abnormalities in the brain serotonin system exist in patients with dementia. The present study was performed in order to investigate whether a peripheral serotonin system marker, the platelet 5-HT2A receptor, is affected in dementia. Thirty-eight patients with Alzheimer's disease (AD), 13 patients with vascular dementia, and 40 healthy controls were included in the study. There were no significant differences in receptor density for 5-HT2A receptor binding between the groups. Affinity of the radioligand to the receptor was significantly lower in AD than in vascular dementia and in the controls (p = .006 and p = .003, respectively), whereas there was no significant difference between the vascular dementia group and the control group. In 12 patients, treatment with citalopram was started due to depression or agitation. This treatment significantly reduced the Behavioral Pathology in Alzheimer's Disease Rating Scale scores (p = .001), but did not affect the platelet 5-HT2A receptor status. There was no correlation between 5-HT2A receptor status before treatment and the therapeutic effect of citalopram. The study indicates that platelet 5-HT2A receptor status is of limited value as a peripheral marker in dementia.

Aged↗
PubMed2000

Effect of caffeine on clozapine pharmacokinetics in healthy volunteers.

AIMS: To assess the effects of caffeine on the pharmacokinetics of clozapine in healthy volunteers. METHODS: This was an open label randomized crossover study in 12 nonsmoking healthy male volunteers. The subjects received a single oral dose of 12.5 mg clozapine in each phase with or without concomitant intake of caffeine (mean dose: 550 mg day-1, range: 400-1000 mg day-1 ). Serum concentrations of clozapine and its metabolites desmethyl-clozapine and clozapine-N-oxide were measured during a 48 h period in each phase. In addition, serum concentrations of caffeine and the metabolite paraxanthine were monitored. RESULTS: A 19% increase in mean clozapine AUC(0,infinity) (P=0.05) and a 14% decrease of mean oral clearance of clozapine were observed during concomitant intake of caffeine (P=0.05) compared with intake of only clozapine. Statistically significant decreases of mean ratios between AUC(0, 12h) for desmethyl-clozapine and AUC(0,12h) for clozapine (-18%), and between AUC(0,12h) for clozapine-N-oxide and AUC(0,12h) for clozapine (-23%) were observed during the caffeine phase (P=0.03 and 0.02, respectively). Oral clearance of clozapine and the ratio AUC(0, 12h) for desmethyl-clozapine/AUC(0,12h) for clozapine were correlated with the paraxanthine/caffeine ratio in serum after intake of caffeine (rs=0.62; P=0.03 and rs=0.77; P=0.003, respectively). CONCLUSIONS: These results suggest that caffeine in daily doses of 400-1000 mg inhibits the metabolism of clozapine to an extent that might be clinically significant in certain individuals.

Adult↗
PubMed2000

Anticonvulsant use during lactation.

The issue of prescribing anticonvulsant drugs during lactation is clinically important, but also complex. Data for some drugs are completely lacking and for other drugs information is only available from single dose or short term studies or case reports. Moreover, limited knowledge exists about the practical impact of the drug concentrations found in breast milk and there are great methodological problems in the assessment of possible adverse drug reactions in infants. Nevertheless, based on current knowledge, some recommendations can be suggested. Treatment with carbamazepine, valproic acid (sodium valproate) and phenytoin is considered compatible with breastfeeding. Treatment with ethosuximide or phenobarbital (phenobarbitone)/primidone should most probably be regarded as potentially unsafe and close clinical monitoring of the infant is recommended if it is decided to continue breastfeeding. Occasional or short term treatment with benzodiazepines could be considered as compatible with breastfeeding, although maternal diazepam treatment has caused sedation in suckling infants after short term use. During long term use of benzodiazepines, infants should be observed for signs of sedation and poor suckling. Only very limited clinical data are available for the new generation anticonvulsant drugs and no clearcut recommendations can be made until further data are present. If it is decided to continue breast feeding during treatment with these drugs, the infant should be monitored for possible adverse effects. In general, the drug should be given in the lowest effective dose, guided by maternal serum or plasma drug concentration monitoring. If breast feeding is avoided at times of peak drug levels in milk, the exposure of the infant can be reduced to some extent. As breast milk has considerable advantages over formula milk, the benefits of continuing breast feeding should always be taken into consideration in the risk-benefit analysis.

Anticonvulsants↗
PubMed1999

Platelet [3H]paroxetine and [3H]lysergic acid diethylamide binding in seasonal affective disorder and the effect of bright light therapy.

BACKGROUND: Seasonal affective disorder (SAD) has been regarded as a melatonin disorder, but the pathophysiological mechanisms of SAD are to a large extent unclarified. Serotonergic mechanisms have also been studied, but they have shown inconsistent results. METHODS: We have compared [3H]paroxetine and [3H]lysergic acid diethylamide (LSD) binding in platelets from 23 SAD patients and 23 controls. Then SAD patients had 4 weeks of light therapy. On the last treatment day new blood samples were drawn. Symptoms before and after light treatment were measured by SIGH-SAD. RESULTS: Bmax for paroxetine binding before light treatment was higher in SAD patients compared to controls and also higher in responders than in nonresponders. Bmax decreased significantly during light treatment. We also found a negative correlation between the two Bmax values before but not after light treatment. There was a negative correlation between Bmax for paroxetine binding before treatment and clinical status after treatment. Patients with reduced Bmax for LSD binding after treatment had a better clinical treatment response. CONCLUSIONS: The present study indicates that serotonin receptor parameters might be suitable in the prediction of clinical response to light treatment.

Adult↗
PubMed1999

[3H]GBR 12935 binding in platelets from poor and extensive cytochrome P-4502D6 metabolizers.

Previous studies have indicated that part of the binding of [3H] [1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl) piperazine dihydrochloride] ([3H]GBR 12935) to human platelets is to a piperazine acceptor site, which might be associated with cytochrome P-450IID6 (CYP4502D6, debrisoquine-4-hydroxylase). Due to mutant CYP4502D6 alleles, 5-10% of Caucasians are poor metabolizers of CYP4502D6 substrates such as debrisoquine and dextromethorphan. In the present study, possible differences in binding characteristics of [3H]GBR 12935 in platelets from CYP4502D6 poor and extensive metabolizers were investigated. The most prominent finding was a gender difference, with males having significantly higher Kd values than females. There were no differences in Bmax. After correction for gender, there was a tendency towards higher Kd values in poor metabolizers than in extensive metabolizers, although the difference was not statistically significant. Whether this finding corresponds to reduced CYP4502D6 activity is a matter of further investigation.

Adult↗