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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 39 (1990), S. 321-325 
    ISSN: 1432-1041
    Keywords: risk factor ; adverse drug reactions ; epidemiological approach ; aspirin ; benzodiacepines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Age by itself is not an important risk factor for ADRs. Age-related changes are the consequence of a number of individual factors, for example morbidity associated with polypharmacy, decline in renal or liver function in the elderly, hypoalbuminaemia, reduced body weight, etc. The relationship between gastrointestinal bleeding and non-steroidal anti-inflammatory drugs can be assessed globally in large cohort studies with access to computerized data, but complete accuracy requires access to the original patient records. The increase in the risk of GI bleeding in users of NSAIDs and aspirin was 50% above that in non-users. About a quarter of ADRs in hospitalized patients seem not to arise from purely pharmacological mechanisms. They are mainly due to allergic, anaphylactoid, or idiosyncratic reactions and to intolerance. In such non-pharmacological reactions, the time of exposure, reaction time, and even dosage may be important factors in identification of the causal drug. The use of benzodiazepines can be optimized by taking into account potency, time of action and the different syndromes encountered after withdrawal. Following long-term use problems of relapse and rebound are being increasingly recognized, in addition to organic withdrawal symptoms. In psychiatric patients extrapyramidal disorders due to neuroleptics are common. The rates of these ADRs differ markedly between various drugs, even after dosages and co-medications are taken into account. Epidemiological screening for potentially carcinogenic drugs can only be done in large cohorts of patients with pre-recorded full information sets as may be found in an HMO (Health Maintenance Organization). The findings of several such studies have been published in specialist cancer journals. However, most of the associations observed should only be viewed as hypotheses for further investigation. In a classical twenty-year follow-up study of a cohort of phenacetin abusers, there was an excess of patients with renal insufficiency and death related to renal and urogenital causes.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 38 (1990), S. 561-565 
    ISSN: 1432-1041
    Keywords: Drug regimens ; compliance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The utility of a new microprocessor-based method for continuous monitoring of compliance in taking solid medicaments has been evaluated. Medication intake in 31 ambulant patients was assessed in a prospective observational study under the conditions of routine practice. The patients (aged 14–87 y, mean 50 y) were receiving long-term drug treatment for various chronic diseases. There was marked interindividual and intraindividual variation in compliance with different drugs. Deviations from the prescribed dosage regimens were caused by omission of doses (22.7% of prescribed doses) and intake of extra doses (5.6% of prescribed doses). Continuous monitoring revealed that in 19% of the monitoring period no medication was taken, in 13% there was partial intake, and in 8% extra doses were taken. Patient-initiated drug holidays occurred in 50% of patients. They were responsible for 76% of the medication-free time. It is concluded, that continuous compliance monitoring is practicable in ambulatory patients. It provides information about the dynamics of drug intake behaviour that cannot be obtained from medical histories or from clinical or laboratory examination. The information could be used effectively in individual patient care and in clinical drug trials.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: Dosage frequency ; Compliance ; drug-intake behaviour ; oestrogen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The objective of the study was to investigate patient compliance with two different dosage regimens. Ethinyloestradiol 80 μg daily was prescribed to 35 female outpatients to be taken as 20 μg four times daily or 40 μg twice daily for 7 days. It was given to standardise cervical mucus before a sperm cervical mucus penetration-test (SCMPT) was performed. Sixty-five patients with primary infertility (mean age 29.9 y) completed the study. Compliance was assessed by microprocessor-based compliance monitoring. Besides compliance (percentage of prescribed doses taken), the adherence of the patients to the dosage schedule was evaluated — ‘regimen compliance’. The latter parameter of drug intake behaviour was calculated by the number of days in which 2 (BID) or 4 openings (QID) were recorded by the electronic monitor. As a third parameter, the deviation from the prescribed dosing intervals, i.e. 12 or 6 h, was also determined. Partial compliance was the predominant finding and only 9 patients (13.8%) were over-compliant. Mean compliance was 75.7% in all 65 patients as a group, range 7.1 to 143%. The mean compliance with the QID regimen was 67% compared to 85% with the BID regimen. ‘Regimen compliance’, the percentage of doses taken on schedule, was 36% and 63% for the QID and BID regimens, respectively. Drug-intake behaviour was more erratic with the QID than the BID regimen, as indicated by the 55% of opening intervals recorded which exceeded the range of 3–9 h (mean: 6 h), compared to only 19% exceeding 6–18 h intervals (mean: 12 h). The present study provides evidence that the prescribed dosage frequency has an impact on drug compliance by patients. From a practical point of view, it seems reasonable to use treatment regimens that are as simple as possible, provided that they are pharmacologically and clinically appropriate.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 39 (1990), S. 577-581 
    ISSN: 1432-1041
    Keywords: Benzbromarone ; elimination phenotypes ; pharmacokinetics ; metabolism ; genetic variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Following oral administration of the uricosuric drug benzbromarone two major metabolites appear in the circulation, 1'-hydroxy-benzbromarone (M1), and a second product (M2) of unknown structure. The plasma concentrations of the parent drug and of M1 and M2 have now been compared in two different elimination phenotypes, 10 subjects who eliminated the drug rapidly (S1–10) and one individual (S11) whose elimination capacity was impaired, presumably due to genetic variation (S11). The AUC (0–96) of the parent drug in S11 was 145 gmg · ml−1 h, and in the other individuals it averaged 18.3 (11.4–24.5) μg · ml−1 h. The plasma elimination half life of benzbromarone was 3.34 (1.77–5.24) h in the rapid eliminators, and 13.08 h in the subject with the elimination defect. The mean plasma elimination half life of the metabolites in S1–10 amounted to 20.1 (11.9–41.2) h for M1, and 17.2 (12.9–30.7) h for M2. In S11 the plasma elimination half life of M1 was prolonged to 76.6 h, and of M2 to 75.4 h. Thus, the elimination defect in S11 was not restricted to the parent drug, but it also involved the two major metabolites M1 and M2. This might be a consequence of a hepatic enzyme deficiency, or be due to impairment of drug excretion.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1041
    Keywords: Midazolam ; lipoprotein binding ; albumin binding ; plasma triglycerides ; intravenous lipid infusions ; severely ill patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Severely ill patients often require total parenteral nutrition including intravenous liqid emulsions concurrently administered with lipophilic drugs. Therefore we investigated whether therapeutic application of a mixed medium chain/long chain triglyceride infusion affects the disposition of midazolam necessary for sedation in patients on artificial respiration. The concentrations of midazolam were measured in unfractionated plasma, and in lipoprotein fractions isolated from ex vivo blood samples, including determination of triglycerides and cholesterol; the albumin level was also analysed. Midazolam in the VLDL fraction was only 0.246 μg·ml−1, whereas the total plasma concentration averaged 1.101 μg·ml−1, and the midazolam content of the LDL plus HDL fractions amounted to 1.771 μg·ml−1. Albumin in these lipoprotein fractions was just as unequally distributed. A lipid infusion resulted in a significant elevation of total triglycerides from 157 to 221 mg·dl−1 and VLDL-triglycerides from 77 to 155 mg·dl−1. The triglyceride content of the LDL plus HDL fraction rose from 102 to 139 mg·dl−1. At the same time the midazolam concentration in unfractionated plasma and in the VLDL and the LDL + HDL fractions decreased to 0.899 μg·ml−1, 0.130 μg·ml−1, and 1.265 μg·ml−1, respectively. Cholesterol and albumin concentrations were not affected. The data show for the first time that a significant increase in plasma triglycerides during an intravenous lipid infusion does not result in accumulation of midazolam in lipoproteins, probably because albumin binding of the drug is very strong. The lack of midazolam trapping is important with respect to the safety of concurrent use of lipophilic drugs and intravenous lipid infusions.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 45 (1993), S. 211-215 
    ISSN: 1432-1041
    Keywords: Compliance monitoring ; Lovastatin ; dose timing ; chronopharmacology ; plasma lipids ; familial hypercholesterolaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The objective of the study was to compare compliance with and the hypocholesterolaemic effect of lovastatin given once daily as a morning or an evening dose. Twenty-four out-patients with familial hypercholesterolaemia were randomly assigned to receive placebo first, then lovastatin 20 mg, to be taken once daily for 4 weeks, either with the breakfast or evening meal, in a single-blind fashion. Drug compliance was assessed by pill counts and continuous electronic monitoring. Two compliance parameters were evaluated, consumption, defined as percentage of prescribed doses taken, and time compliance, the percentage of total dosing events recorded within defined intervals (6.00–10.00 h, and 17.00–21.00 h), for the morning and evening regimes. Both regimes satisfactorily reduced the total and LDL-cholesterol concentrations, and there was no significant difference in the extent of the reductions. Pill counts overestimated compliance, as revealed by the monitoring method. The times of actual consumption of doses by the patients often differed from that prescribed, predominantly in patients who were told to take the evening dose. Partial time compliance may have confounded the efficacy of the drugs. Electronic compliance monitoring appears to be particularly useful in chronopharmacological studies.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 39 (1990), S. 173-176 
    ISSN: 1432-1041
    Keywords: Benzbromarone ; elimination ; phenotype distribution ; drug metabolism ; drug polymorphism ; adverse reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma benzbromarone concentration-time profile in a healthy subject who retained the compound much longer than other individuals is described. The data suggested that determination of the 24 h plasma concentration of the parent drug after a single oral dose of 100 mg benzbromarone would be an appropriate procedure to determine the elimination phenotype. Based on this procedure, 148 of 153 healthy individuals (97%) in a population study were found to eliminate benzbromarone rapidly. In one subject the 24 h benzbromarone plasma concentration was very similar to the that observed in the individual who had been more fully characterized. Four participants gave intermediate results. The data are compatible with a bimodal or trimodal distribution of different benzbromarone elimination phenotypes.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 46 (1994), S. 455-459 
    ISSN: 1432-1041
    Keywords: Ciclotropium ; heart rate ; pharmacokinetic/pharmacodynamic modelling ; effect compartment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Ciclotropium is a recently developed parasympathicolytic agent. Plasma concentration and heart rate increase (the most prominent anticholinergic effects) were measured in 12 healthy subjects before, during and after a 15-min intravenous infusion of 10 mg ciclotropium. The effect was described by using either a linear or a nonlinear (E max) effect model linked to a linear three-compartment kinetic model via an effect compartment. Maximum heart rate increase was 33 (10) beats·min−1, and half-value duration of effect was 41 (9) min. Total plasma clearance was 0.51 (0.13) l·min−1, and mean terminal elimination half-life was 12 (4) h, whereas the equilibration half-lives of drug removal from the effect compartment ranged from 2 to 14 min.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: A 2.1 kb DNA segment carrying the purine-cytosine permease gene (FCY2) of Saccharomyces cerevisiae was sequenced, the primary structure of the protein (533 amino acids) deduced and a folding pattern in the membrane is proposed for the permease protein. Expression of the FCY2 gene product requires a functional secretory pathway and is reduced in mnn9, a mutant strain deficient in outer chain glycosylation. The FCY2 gene was mapped on the right arm of chromosome V close to the HIS1 gene.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 65 (1994), S. 1671-1673 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: GaP films, epitaxially grown at a low temperature (LT) of ∼200 °C by gas source molecular beam epitaxy, were reported recently to have excess phosphorus. In this letter, we report on the quantitative determination of the excess phosphorus in the LT films, using various approaches. Analytical scanning transmission electron microscopy, double-crystal x-ray diffraction, and particle-induced x-ray emission showed that the LT GaP films incorporated excess phosphorus of ∼0.6–2 at. %. The amount of excess phosphorus estimated from Raman scattering measurements, using the LO-TO phonon frequency splitting data of the as-grown LT GaP and bulk GaP, was in general agreement with those obtained from other techniques.
    Type of Medium: Electronic Resource
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