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Biomedical subjects

P M Edelbroek

Publications and source records attributed to P M Edelbroek.

At least 19 recordsLinked to original sources
PubMed1996

Photosensitive epilepsy: a model to study the effects of antiepileptic drugs. Evaluation of the piracetam analogue, levetiracetam.

The experimental antiepileptic drug, levetiracetam (UCB L059), a piracetam analogue has been investigated in photosensitive patients in the "photosensitivity model", an early phase II study. A total of 12 patients (10 females, 2 males) with a mean age of 21.5 years (range 13-38) were investigated during a 3 day period in 3 centres (France, The Netherlands, Germany), using the same standardised method. The subjects were either treated with a single oral dose of 250 mg, 500 mg, 750 mg or 1,000 mg. In addition, 4 patients took 250 mg b.i.d. for 3-5 days, after which they were re-examined. In 9 of 12 photosensitive patients (75%) a clear suppression (3 patients) or abolishment (6 patients) of IPS evoked photoparoxysmal EEG responses was found. This effect appeared to be dose-dependent, the higher the dose the greater the effect; complete abolishment was only seen at dosages of 750 mg and 1,000 mg, occurring at peak plasma levels and lasting between 6 and 30 h. There was no indication of pharmacokinetic interaction with concomitant antiepileptic drugs such as valproic acid, ethosuximide or phenobarbitone. No serious side-effects were seen and some patients reported enhancement of their mood. Two patients with myoclonic jerks noticed a clear reduction of their myoclonus, although this was not one of the objectives of the study. In conclusion, levetiracetam showed a clear antiepileptic effect in the photosensitivity model.

Administration, Oral↗
PubMed1994

High-performance liquid chromatographic and megabore gas-liquid chromatographic determination of levetiracetam (ucb L059) in human serum after solid-phase extraction.

For monitoring drug levels of the new potential anticonvulsant drug levetiracetam (ucb L059) in human serum, two assay methods were developed and compared. A solid-phase extraction procedure was followed by either reversed-phase HPLC separation and UV-detection or GLC separation using cold on-column injection on a megabore column and nitrogen-phosphorous detection. Absolute recovery of the drug exceeded 97%. Precision and accuracy values for the 16.0 micrograms/ml quality control sample were 2.4% and 101 +/- 5% (n = 10), respectively, for the GLC method. Precision and accuracy values for the 12.1 micrograms/ml quality control sample were 1.0% and 100 +/- 1% (n = 7), respectively, for the HPLC method. Agreement between both methods was excellent (r = 0.993). Both methods are suitable for pharmacokinetic studies and therapeutic drug monitoring as well. Serum level data for levetiracetam in a patient on chronic antiepileptic medication are presented.

Autoanalysis↗
PubMed1992

Biochemical measures in patients with a somatoform pain disorder, before, during, and after treatment with amitriptyline with or without flupentixol.

The possible relationship between a number of biochemical parameters and measures of pain and depression was studied in chronic pain patients without a major depression. In a double-blind crossover study, patients were treated with amitriptyline combined with a low dose of flupentixol or placebo. We investigated whether pretreatment biochemical values correlated with initial data on pain and/or depression, or whether they had predictive value for treatment outcome. We also studied systematically the effect of both treatment regimes on the biochemical parameters themselves and their relation to the plasma levels of amitriptyline. From our results, the possible involvement of the serotonin system in somatoform pain disorder is confirmed and no direct relation with the noradrenergic system could be inferred. The lack of involvement of a number of putative, depression-related, biochemical parameters suggests that affective disorders and pain syndromes do not share all mechanisms in common.

Adult↗
PubMed1992

Increased neurotoxicity of arsenic in methylenetetrahydrofolate reductase deficiency.

A 16-year-old girl from Surinam presented with mental deterioration and severe paraparesis with areflexia and bilateral Babinski signs. Laboratory examination showed a hyperhomocysteinemia that was caused by 5,10-methylene-tetrahydrofolate reductase (MTHFR) deficiency. In addition, urine samples contained large amounts of arsenic. An open bag with the pesticide copper acetate arsenite was found to be the source of exposure. In remethylation defects such as MTHFR deficiency, the concentration of methyldonors is severely reduced. As arsenic is detoxified by methylation, we suggest that the MTHFR deficiency in this girl might explain the fact that of all family members exposed to arsenic, only she developed severe clinical signs and symptoms of arsenic poisoning.

Adolescent↗
PubMed1992

Conventional and controlled release valproate in children with epilepsy: a cross-over study comparing plasma levels and cognitive performances.

We studied plasma levels and behavioural effects of a newly developed controlled release formulation of valproate (VPA-CR) in children with epilepsy. Valproate plasma levels and performances in attention and vigilance tasks were monitored during a 12-h period (daytime), both during monotherapy of conventional valproate (VPA) and 4 weeks after switching to a similar dosage of VPA-CR taken once daily. There was no significant difference between the two formulations with respect to mean diurnal trough and peak valproate plasma levels, and to mean fluctuation. The significantly higher Cmax/Cmin ratio during VPA-CR seems mainly due to low valproate plasma levels early in the morning. Neuropsychological assessment showed no significant differences, either between patients and controls, or within patients and controls when comparing the results obtained on the VPA and VPA-CR day. During both VPA and VPA-CR treatment, no correlation was found between cognitive performance and valproate plasma levels. The advantage of VPA-CR is that the once daily regimen may increase compliance and is more convenient for schoolchildren.

Adolescent↗
PubMed1991

Analysis of bismuth in serum and blood by electrothermal atomic absorption spectrometry using platinum as matrix modifier.

Bismuth-containing medicines have been used for years, but there is a lack of clinically applicable methods for measuring bismuth in body fluids. We describe a sensitive, accurate and precise method for analysis of bismuth in blood and serum, which is suitable both for monitoring purposes and for further investigations into the biokinetics and safety of bismuth. Bismuth was quantitated with electrothermal atomic absorption spectrometry with Zeeman background correction. In the furnace programme a cool-down step was introduced and platinum was used as a matrix modifier. Recovery for 40 micrograms/l is 93.7 +/- 4.6% (mean +/- SD) from serum and 92.8 +/- 5.4% from blood; within-day precision (n = 10) at 40 micrograms/l is 3.2% for serum and 4.2% for blood. Day-to-day precision at 40 micrograms/l (n = 10) was 4.5% for serum and 4.0% for blood. The detection limit is 0.7 microgram/l for serum and 1.0 microgram/l for blood. Blood samples have to be collected in glass tubes and stored at -20 degrees C.

Animals↗
PubMed1991

Does addition of low-dose flupentixol enhance the analgetic effects of low-dose amitriptyline in somatoform pain disorder?

In a double-blind, crossover study, the effects of 75 mg amitriptyline alone during 5 weeks on pain intensity were compared with the effects of a combination of 75 mg amitriptyline and 3 mg flupentixol during 5 weeks in 34 patients with somatoform pain disorder. Both treatments resulted in a statistically significant reduction in pain. However, pain reduction in the combined treatment did not differ from that in the treatment with amitriptyline as a single drug. Neither tardive dyskinesias nor other serious side effects were observed. The results do not support the clinical practice of adding low-dose neuroleptics to low-dose antidepressants in the treatment of somatoform pain disorder.

Adult↗
PubMed1991

Influence of sulphasalazine and mesalazine on cellular and biochemical oxygen metabolite production. Effect of in vivo administration and an in vitro analysis.

Oxidative damage has been implicated in the pathogenesis of inflammatory bowel disease. In the present study sulphasalazine and mesalazine (5-aminosalicylic acid) in vitro were shown to possess scavenging activity and to attenuate the production of oxygen metabolites by neutrophils. In a double-blind randomized crossover study, with five patients with inflammatory bowel disease in remission and four healthy controls, we evaluated the influence of in vivo administration of sulphasalazine and mesalazine on the neutrophil oxygen metabolite production in vitro. Apart from a small but significant increase in the neutrophil H2O2 and O2 production by sulphasalazine, in particular in controls, in vivo administration of both drugs hardly affected the oxygen metabolite-producing capacity of the cells. This observation was confirmed by in vitro preincubation of neutrophils with the drugs and subsequent oxygen metabolite production analysis. It is concluded that sulphasalazine and mesalazine do not influence the oxidative capacity of neutrophils, but scavenge and attenuate the production of oxygen metabolites when present in the immediate surroundings of the cells. Thus, protection against oxidative damage is definitely one of the modes of action of these drugs.

Aminosalicylic Acids↗
PubMed1990

Analysis of phenprocoumon and its hydroxylated and conjugated metabolites in human urine by high-performance liquid chromatography after solid-phase extraction.

The anticoagulant phenprocoumon is mainly metabolized in humans to hydroxylated metabolites and their glucuronides. A method is described for the determination of phenprocoumon, 4'-hydroxyphenprocoumon, 6-hydroxyphenprocoumon, 7-hydroxyphenprocoumon, and their glucuronide and sulphate conjugates in human urine. Reversed-phase high-performance liquid chromatography is performed after selective extraction with disposable quaternary amine columns of untreated, and beta-glucuronidase- or sulphatase-treated urine samples. Urinary excretion data are presented for total, glucuronidated, sulphated and free phenprocoumon, 4'-hydroxyphenprocoumon, 6-hydroxyphenprocoumon and 7-hydroxyphenprocoumon in twelve patients after an average daily dosage of 1.3-4.2 mg phenprocoumon.

Adult↗
PubMed1990

A simplified assay for measurement of cytosine arabinoside incorporation into DNA in Ara-C-sensitive and -resistant leukemic cells.

The assays for the detection of unlabeled 1-beta-D-arabinofuranosylcytosine (cytosine arabinoside, Ara-C) incorporation into DNA was simplified. The procedure includes DNA isolation from leukemic cells, quantification of DNA concentrations, breakdown by enzymatic digestion of DNA to nucleosides and a radioimmunoassay (RIA) using an antibody against Ara-C. Different techniques for quantification of DNA concentrations are compared. A fluorimetric technique using Hoechst 33258 is preferred because it is the most specific method. Comparison of this RIA assay with measurement of [3H]-Ara-C/DNA formation under similar conditions in HL-60 cells showed a correlation of 0.99. Ara-C incorporation into DNA of leukemic cells was studied using two rat-leukemia cell lines, one of which is sensitive to Ara-C and the other is an Ara-C-resistant wild type: BNML-Cl/0 and BNML-Cl/Ara-C, respectively. The results showed that Ara-C is incorporated when the cells are incubated at concentrations equal to or higher than the Ara-C concentration that induces 50% growth inhibition after 48 h incubation (IC50). This implies that at lower Ara-C concentration, i.e. levels that do not induce cytotoxicity, Ara-C is not incorporated into DNA. Similar results were obtained with human HL-60 myeloid leukemia cells. The detection limit of this assay is 2 pmol/ml Ara-C; therefore, the assay is more sensitive than measurement of Ara-C triphosphate (Ara-CTP), the only metabolite that can be measured in leukemic cells from patients after in vivo Ara-C administration. On the basis of in vitro studies, the finding of detectable Ara-C/DNA levels in vivo is expected to correlate with cytotoxicity; whether or not the Ara-C/DNA level itself is informative remains to be evaluated.

Animals↗
PubMed1990

Severe lidocaine intoxication by cutaneous absorption.

A severe lidocaine intoxication by cutaneous absorption is described. Data are presented to show a significant absorption of lidocaine through diseased skin when lidocaine cream is used as a local anesthetic. Awareness of this route of intoxication might be important in patients in whom neurologic or psychiatric symptoms develop while large amounts of lidocaine cream are being used.

Female↗
PubMed1990

Low dose amitriptyline in chronic pain: the gain is modest.

In the double-blind placebo-controlled study presented here, the effects were investigated of a low dose of amitriptyline (75 mg) in patients with chronic pain of various origins. The active drug was superior to placebo in reducing pain intensity. The reduction was small. In the second treatment week, the amitriptyline treated patients slept longer. No differences between active drug and placebo were found with respect to daily activities or use of analgesics. Based on our data and those of other studies, it is concluded that amitriptyline (and other antidepressants) in low doses does have a positive effect on the intensity and some other aspects of chronic pain, but that the effect is modest. It must be kept in mind that chronic pain is a very treatment-resistant condition. Therefore, even modest positive effects may be worthwhile.

Adult↗
PubMed1990

Detection of drug interactions with single dose acenocoumarol: new screening method?

In this study, a design for the evaluation of drug interactions with an oral anticoagulant drug was investigated. The interaction between a single dose of acenocoumarol and cimetidine or pentobarbitone was studied. Nine healthy volunteers received three treatments: 1) 10 mg acenocoumarol in combination with cimetidine, 2) 10 mg acenocoumarol in combination with placebo, 3) 10 mg acenocoumarol after one week pretreatment with pentobarbitone. The pharmacokinetics and the pharmacodynamics of acenocoumarol were monitored for 36 h. In all subjects the plasma concentration of acenocoumarol remained consistently higher during cimetidine treatment and consistently lower after pentobarbitone pretreatment compared to placebo treatment. Cimetidine increased the anticoagulant response of acenocoumarol as measured by the Thrombotest and pentobarbitone decreased this response in all subjects. It is concluded from this study that both pharmacokinetic and pharmacodynamic drug interactions with acenocoumarol (and presumably other oral anticoagulants) can be detected after single doses, possibly obviating the use of long-term anticoagulation in healthy volunteers.

Acenocoumarol↗
PubMed1987

Therapeutic drug monitoring of amitriptyline: impact of age, smoking and contraceptives on drug and metabolite levels in bulimic women.

Concentrations of amitriptyline (AT), nortriptyline (NT) and E-10-hydroxynortriptyline (E-10-OH-NT) were measured in 18 women with bulimia receiving 100 mg AT/day for at least 6 wk. After onset of treatment between days 36 and 57 there is a decrease in AT and an increase in E-10-OH-NT concentrations, probably due to an autoinductive effect on hydroxylation. The estimated mean (+/- SD; range; n) elimination half-life time of AT was 14.0 (+/- 7.8 h; 7.5-38.5 h; 14). On day 36, AT concentrations in females using oral contraceptives (OC) were higher than in non-users of OC, which indicates inhibition of AT metabolism by OC. In all smokers the E-10-OH-NT concentrations on day 36 were lower than in non-smokers. Our findings suggest induction of N-demethylation and glucuronidation by smoke components.

Adolescent↗