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  • 1
    ISSN: 1432-1041
    Keywords: Key words Antidepressants ; Prescription database; utili zation ; tolerability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To study whether the newer antidepressants have changed the patterns of antidepressant use, and whether the claimed better adverse effect profile of the newer antidepressants is reflected in their use as monitored by a prescription database. Method: By means of a prescription database (OPED), the use of antidepressants from 1991 to 1993 in Odense, Denmark, was analysed. Results: The 1-year prevalence of antidepressant use increased significantly from 1.60% to 2.00%, which still is below the claimed 1-year prevalence of depression of at least 5%. The increase was mainly due to a rapidly increasing use of the newer antidepressants, accompanied by a moderate decline in the use of older antidepressants (mainly tricyclic antidepressants). The patterns of antidepressant use were very polymorphic, with about 5% being on continuous use for all 3 years and groups of each 20–30% being treated with: (1) several series or (2) one series or (3) only by one prescription. The share of patients presenting only one prescription (20%) was the same for older and newer antidepressants. Likewise, the rate of shifts from older to newer antidepressants or vice versa was the same (7% vs 6%). The duration of treatment did not differ much between older and newer antidepressants. Relative to the defined daily dose (DDD), the older antidepressants were given in much lower doses (median 0.63 DDD) than the newer antidepressants (median 1.05 DDD). Conclusion: It is concluded that many depressed patients are still not receiving antidepressant treatment and that the claimed better adverse effect profile of the newer antidepressants was not clearly reflected in their use.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 8 (1975), S. 343-347 
    ISSN: 1432-1041
    Keywords: Nortriptyline ; pharmacokinetics ; man ; two compartment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of nortriptyline have been assayed in four subjects after intravenous infusion of 57 mg nortriptyline hydrochloride. The data were evaluated according to a two compartment open model. The calculated best-fitting curves were in good agreement with the experimental data, better than could be expected from a simpler model. This justifies the assumption that the kinetics of nortriptyline in man may be described by this model with an appropriate input function. The data permitted estimation of all the parameters of the model. The meaning of the parameters is discussed, particularly in relation to individual variation.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 30 (1986), S. 43-49 
    ISSN: 1432-1041
    Keywords: imipramine ; desipramine ; hydroxymetabolites ; plasma concentration monitoring ; dose-dependent kinetics ; drug interaction ; levomeprazine ; perphenazine ; therapeutic response ; sparteine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seventeen hospitalized patients (age 39–66 years), received a loading dose of 100 mg imipramine HCl and then 50 mg b.i.d. The 12-h plasma concentration at steady-state varied between 40–637 nmol/l for imipramine, 49–1148 nmol/l for desipramine and 89–1603 nmol/l for imipramine + desipramine. Guided by plasma level monitoring, a final therapeutic plasma level between 548–910 nmol/l for imipramine + desipramine was achieved (therapeutic dose range: 50–400 mg/day). Mean time to reach the therapeutic level was 19 days. The mean 2-OH-imipramine/imipramine ratio was 0.24 and mean 2-OH-desipramine/desipramine ratio was 0.56. There was a significant intrapatient correlation between the two ratios, both during 100 mg imipramine/d and at the therapeutic dose level. A low ratio was associated with high imipramine and particularly with a high desipramine level. Well defined steady state levels were established at two different dose levels in 12 patients and at three dose levels in 5 patients. With increasing dose there was a marked and disproportionate rise in the desipramine level and to some extent in the imipramine level. Saturation of imipramine and desipramine hydroxylation appeared to be responsible for the dose-dependent kinetics. Concomitant treatment with levomepromazine and perphenazine in one patient resulted in a significant rise both in imipramine and desipramine concentration, apparently due to inhibition of the hydroxylation. Eleven out of twelve endogenously depressed patients responded completely to treatment, whereas the response was poor in the non-endogenously depressed patients despite optimal drug levels.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 34 (1988), S. 83-86 
    ISSN: 1432-1041
    Keywords: thiazide diuretics ; beta-adrenoceptor ; calcium antagonists ; adverse drug reactions ; treatment non-compliance ; hospital admission
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 426 consecutive patients admitted to a Danish University Department of Cardiology have been studied. Drug intake prior to admission by each patient was ascertained from medical records and personal interviews. Adverse drug reactions (ADR) were the primary cause of admission in 49 patients (11.5%), and 16 patients (3.8%) were admitted due to drug non-compliance (DNC). Thiazide diuretics, beta-adrenoceptor blocking agents and calcium antagonists accounted for almost 60% of all the ADR-related admissions. Patients admitted for ADR took significantly more drugs than patients admitted for other reasons. DNC was not correlated with the number of prescribed drugs. It is concluded that drug-related hospital admissions are an important medical and economic problem. Most of the ADRs were well-known and predictable actions of the drugs, and could have been avoided by more careful clinical and laboratory monitoring of the patients. Most of the DNC, too, could have been avoided by giving better information to the patients.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 537-547 
    ISSN: 1432-1041
    Keywords: sparteine ; debrisoquine ; pharmacogenetics ; oxidation polymorphism ; clinical significance ; oxidative drug metabolism ; genetic control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The sparteine/debrisoquine oxidation polymorphism results from differences in the activity of one isozyme of cytochrome P450, the P450db1 (P450 IID1). The oxidation of more than 20 clinically useful drugs has now been shown to be under similar genetic control to that of sparteine/debrisoquine. The clinical significance of this polymorphism may be defined by the value of phenotyping patients before treatment. The clinical significance of such polymorphic elimination of a particular drug can be analyzed in three steps: first, does the kinetics of active principle of a drug depend significantly on P450db1?; second, is the resulting pharmacokinetic variability of any clinical importance?; and third, can the variation in response be assessed by direct clinical or paraclinical measurements? It is concluded from such an analysis that, in general, the sparteine/debrisoquine oxidation polymorphism is of significance in patient management only for those drugs for which plasma concentration measurements are considered useful and for which the elimination of the drug and/or its active metabolite is mainly determined by P450db1. At present, this applies to tricyclic antidepressants and to certain neuroleptics (e.g. perphenazine and thioridazine) and antiarrhythmics (e.g. propafenone and flecainide). Phenotyping should be introduced in to clinical routine under strictly controlled conditions to afford a better understanding of its potentials and limitations. The increasing knowledge of specific substrates and inhibitors of P450db1 allows precise predictions of drug-drug interactions. At present, the strong inhibitory effect of neuroleptics on the metabolism of tricyclic antidepressants represents the best clinically documented and most relevant example of such an interaction.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 37 (1989), S. 155-160 
    ISSN: 1432-1041
    Keywords: imipramine ; desipramine ; quinidine ; sparteine oxidation ; cytochrome P450 isoforms ; genetic polymorphism ; drug interaction ; metabolic clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary On separate occasions 6 extensive metabolizers of sparteine took a single oral dose of 100 mg imipramine and desipramine before and during the intake of quinidine sulphate 200 mg/day. During quinidine the total oral clearance of imipramine on average was reduced by 35%, and that of desipramine by 85%. The clearance of imipramine via demethylation was not significantly reduced during quinidine administration, whereas its clearance by other pathways, largely 2-hydroxylation, was reduced by more than 50%. 2-OH-Imipramine and 2-OH-desipramine were detected in plasma before (maximum concentrations 30–100 nmol · l−1) but not during quinidine. It appears that quinidine is a potent inhibitor of the sparteine/debrisoquine oxygenase, P450dbl, which is responsible for the 2-hydroxylation of imipramine and desipramine, but not of the P450 isozyme responsible for the demethylation of imipramine.
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  • 7
    ISSN: 1432-1041
    Keywords: clinical pharmacology ; European Medical Schools ; teaching ; organization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A World Health Organisation (European Regional Office) working party has been established to review the progress of clinical pharmacology in European countries. As part of this review a questionnaire on the teaching of chlinical pharmacology was sent to the Deans of all 350 medical schools in the region. Very few replies were received from U.S.S.R., Greece and Portugal and these countries' returns were not analysed further. The overall compliance rate (excluding these countries) was 82% with a figure of 84% from Western Europe and 74% from Eastern Europe. An average time of 96 h (range 0–320) was devoted to pharmacology teaching in the medical curriculum in Western Europe with 124 (0–240) h in Eastern Europe. In contrast 28 h (0–210) was devoted to clinical pharmacology teaching in Western Europe and 27 h (0–90) in Eastern Europe. On average in Western Europe each medical school had 2 individuals trained in clinical pharmacology with 1.3 posts in the subject and the figures for Eastern Europe were 2.3 and 1.1 respectively. However these figures hide a wide variance in the teaching of clinical pharmacology. Particularly in Western Europe there are a number of medical schools in Italy, Spain and the Federal Republic of Germany (FRG) where clinical pharmacology is not taught and there is a dearth of individuals trained in the subject. Every effort to encourage clinical pharmacology and its teaching should be made, particularly in these countries.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 50 (1996), S. 161-165 
    ISSN: 1432-1041
    Keywords: Key words Sumatriptan ; Migraine treatment; prescription database ; heavy drug consumption ; pharmacoepidemiology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Sumatriptan is highly efficacious in aborting acute attacks of migraine. Owing to recent reports of misuse of sumatriptan, we performed a study of its use in a Danish population. Methods: Data were retrieved from a prescription database covering a period of 27 months after release of the drug. Consumption was described by the defined daily dose (DDD) unit and total individual consumption during the period was calculated. Those who received more than one prescription for sumatriptan were classified according to peak use of sumatriptan into high (≥ 60 DDD/31 days) (n = 45), intermediate (30–59 DDD/31 days) (n = 127) and low (〈 30 DDD/31 days) (n = 1423) consumption groups. Individual usage of other medication was described. Results: We identified 2,878 users of sumatriptan, of whom 1,283 (45%) only redeemed one prescription. The use of sumatriptan was highly skewed. The 1% heaviest users accounted for 20% of the total consumption. The median total individual consumption of sumatriptan was 500 DDD, 192 DDD, and 24 DDD in the three groups of multiple redeemers, respectively. Pronounced differences in the total amounts of opioids and ergot alkaloids used were also found, with the high peak consumption group being the heaviest consumers of all drug categories, although half of them had only received large doses of sumatriptan. Fifty seven % of high peak users redeemed more than 29 DDD of sumatriptan within one month of initiation of treatment. The 45 high peak users had received the bulk of their medication, largely in tablet formulation, from 31 prescribers. The data points to rebound headache as a plausible underlying mechanism, but incorrect use of sumatriptan for migraine prophylaxis is also a possibility. Overuse of sumatriptan has serious economic consequences and its long-term health effects are not known.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 28 (1985), S. 725-726 
    ISSN: 1432-1041
    Keywords: d-propoxyphene ; norpropoxyphene ; pharmacokinetic changes ; deep peripheral compartment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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  • 10
    ISSN: 1432-1041
    Keywords: amitriptyline ; imipramine ; clomipramine ; antidepressant overdose ; clinical effects ; pharmacokinetics ; cardiotoxicity ; maprotiline ; doxepine ; nortriptyline ; opipramol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty-nine cases of self-poisoning with antidepressants (amitriptyline, imipramine, clomipramine, maprotiline, doxepine, nortriptyline, opipramol) were examined by frequent observation of CNS effects, heart rate, blood pressure and standard ECG, 24 h-ECG-monitoring, measurement of systolic time intervals, EEG recordings and frequent measurement of serum levels of antidepressants and primary metabolites. None of the patients died. Maximum total serum antidepressant level (parent compound + desmethyl metabolite) ranged from 20 to 2200 µg/l, with concentrations above 500 µg/l in 11 cases. The serum amitriptyline concentration remained high for 3–4 days in some of the severely intoxicated patients and the decay curves were compatible with partly saturated elimination. A degree of unconsciousness and the occurrence of excitation and hallucinations were generally seen in cases with total serum antidepressant levels above 500 µg/l. Grand mal seizures occurred more frequently at high antidepressant levels, but could not be predicted from the EEG recordings. Increased heart rate and prolonged QRS- and QTc-intervals were significantly correlated with the total serum antidpressant level. 24 h-ECG-monitoring revealed no serious arrhythmias or instances of heart block. Hypotension was only seen initially in few patients. Systolic time interval measurements showed changes suggesting impaired myocardial performance (elevated PEP/LVET ratio) at intermediate (60–500 µg/l) but not high (〉500 µg/l) total serum antidepressant levels. Measurement of serum concentration in antidepressant intoxication is important for identification of patients with high serum levels and the corresponding risk of developing toxic reactions, and to exclude patients with a low concentration who do not require intensive observation.
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