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Biomedical subjects

P M Edelbroek

Publications and source records attributed to P M Edelbroek.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1986

Analgesic and antidepressive effects of low-dose amitriptyline in relation to its metabolism in patients with chronic pain.

The analgesic and antidepressive effects of amitriptyline (AT) in relation to its kinetics and metabolism were studied in 19 outpatients with chronic pain who received a daily dose of 75 mg AT for at least 6 weeks. Riboflavin was added to the medication to check compliance. On days 0, 4, and 8 and weeks 3, 6, 9, and 12 after the start of dosing, blood samples were drawn from the patients 10 +/- 1 hours after the first morning dose and a sample of the first morning urine was taken to check riboflavin. Serum levels of AT and its metabolites, especially nortriptyline (NT) and E-10-hydroxy-nortriptyline (E-10-OH-NT), were measured by HPLC. On day 0 and at 3, 6, and 12 weeks the severity of depression was scored by means of a self-rating depression scale and pain intensity scores were measured. In addition, after 6 weeks of dosing patients estimated their percentage of pain in comparison with baseline. Mean (+/- SD) steady-state concentrations of AT, NT, and E-10-OH-NT were 36 +/- 23.5, 28 +/- 14.9, and 52 +/- 23.7 micrograms/L, respectively, in male patients (n = 8; age 45 +/- 7.4 years) and 34 +/- 14.6, 45 +/- 25.1, and 40 +/- 15.6 micrograms/L, respectively, in female patients (n = 11; age 46 +/- 6.8 years). There was a significant sex-related difference in the NT/AT ratio, which was higher in women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

In vivo studies on high-dose 1-beta-D-arabinofuranosylcytosine (HDara-C) and 1-beta-D-arabinofuranosyluracil (ara-U) with respect to pharmacokinetics, cell kinetics, and cytotoxicity in a rat myelocytic leukemia model (BNML).

From the current studies it can be concluded that comparing the ara-C catabolism to ara-U in leukemic rats and leukemic patients, this process is about 100 times more pronounced in human leukemic cells. The low deaminase activity in leukemic rats probably explains the slow plasma ara-C disappearance curve in the BNML. No cytotoxic effect of ara-U with respect to LCFU-S reduction could be observed, nor did ara-U enhance the cytotoxic effect ara-C in the BNML. These studies have increased the understanding of the relation between ara-C, ara-U plasma levels and deaminase activity.

Animals↗
PubMed1984

Food does not effect in bioavailability of theophylline from Theolin Retard.

The absorption of theophylline from a sustained release tablet preparation ( Theolin Retard 300 mg) was studied in 10 subjects both when fasting and immediately after a standardized breakfast. Intravenous aminophylline was used as the reference material. Food did not influence the absorption from Theolin Retard. The bioavailability was complete (93% after 30 h) both with and without food, and no difference was found in the time to peak of the plasma concentration curve (7 h), or the mean residence time (14 h). The absorption characteristics, with predominantly zero order kinetics, did not change with concomitant intake of breakfast.

Adult↗
PubMed1984

Amitriptyline metabolism in relation to antidepressive effect.

The relationship between amitriptyline (AT) metabolism and clinical response was studied in 14 outpatients treated with a daily dose of 150 mg AT. Riboflavin was added to the medication to check compliance. On days 0, 2, and 7 and at 3, 6, 9, and 13 wk after onset of therapy, blood samples were drawn from the patients 3 (+/- 0.5) hr after the first morning dose and a sample of the first morning urine was taken to check riboflavin. Serum levels of AT and its metabolites, nortriptyline (NT), E- and Z-10-hydroxynortriptyline (E- and Z-10-OH-NT), total (E + Z) 10-hydroxyamitriptyline (tot-10-OH-AT), and desmethylnortriptyline (DNT), were measured by means of HPLC while minimizing adsorption onto glass. On day 0 and after 6 and 13 wk the severity of the depressive disorder was scored by means of the self-rating depression scale of Zung.28 Mean steady-state concentrations of AT, NT, and E-10-OH-NT were in the order of 100 micrograms/l and tot-10-OH-AT and Z-10-OH-NT approximated 20 micrograms/l. DNT concentrations were under 15 micrograms/l. There was great variation in metabolic pattern between patients. After 6 wk concentrations of all compounds were approximately 15% lower than at 3 wk, indicating a weak autoinducible effect of AT or its metabolites. Steady-state concentrations of AT correlated well with that of NT (r = 0.64; P less than 0.05) but not with that of E-10-OH-NT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Experience with a screening method for laxative abuse.

1 Abuse of laxatives may lead to a variety of serious disorders which are usually difficult to recognize because of the heterogenicity of the toxic effects. 2 In order to facilitate the diagnosis of chronic laxative poisoning, a laboratory screening method for the detection of colonic stimulants in urine has been designed and has been applied in practice over a three-year-period. 3 During this period, 157 samples from 81 patients were sent to the laboratory. Fifteen patients (18.5%) were definitely shown to use self-prescribed laxatives. 4 Next to the diphenolic compounds: bisacodyl, phenolphthalein and bisoxatin, the anthraquinone derivative rhein, a metabolite of vegetable laxatives, was found in several cases. In the urine of three patients a substance resembling rhein was found, which was shown to be aloe-emodin. 5 It is concluded that chronic self-poisoning with laxatives is a fairly common disorder than can easily be overlooked. Laboratory screening of the urine of suspected patients is an economic and reliable method for its diagnosis.

Cathartics↗
PubMed1982

Liquid-chromatographic determination of amitryptyline and its metabolites in serum, with adsorption onto glass minimized.

To study correlations between the concentrations, in serum, of amitriptyline and its most important metabolites with clinical response in patients, we developed a "high-performance" liquid-chromatographic method for routine determination of amitriptyline, nortriptyline, total 10-hydroxy-amitriptyline, desmethylnortriptyline, and E(trans)- and Z(cis)-10-hydroxynortriptyline. These compounds are extracted from 1 mL of alkalinized serum into hexane/isoamyl alcohol (99/1 by vol). Perazine is the internal standard. To minimize irreversible adsorption of the drugs onto the glassware, 5 micrograms of maprotiline is added to the organic phase just before evaporation. After a 10-min resolution on a silica column eluted with acetonitrile/methanol/NH4OH (1 mol/L), absorbance is measured at 240 nm. Only chlorimipramine, doxepin, procainamide, and N-acetylprocainamide may interfere with assay of the compounds that probably are therapeutically relevant: amitriptyline, nortriptyline, and E-10-hydroxynortriptyline. Uremia, lipemia, and icterus also do not affect the analysis.

Adsorption↗