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Biomedical subjects

F P Meyer

Publications and source records attributed to F P Meyer.

At least 19 recordsLinked to original sources
PubMed2003

Therapeutic drug monitoring of clozapine and relapse--a retrospective study of routine clinical data.

OBJECTIVE: Therapeutic drug monitoring (TDM) of the atypical antipsychotic drug clozapine is recommended. Clinical studies have indicated a therapeutic window for clozapine serum levels in schizophrenic and schizo-affective patients during acute treatment, i.e. for patients who do not respond to treatment with typical antipsychotics. However, despite the frequent use of clozapine also in maintenance treatment, very few data are available showing the relationship between serum levels of clozapine and the prevention of relapse. Thus, the primary objective of the study was to investigate the relationship between serum levels ofclozapine and relapse during maintenance treatment. METHODS: A retrospective study of routine TDM-data was conducted. Samples obtained on an acute treatment ward from patients with < 4 days hospitalization (recent admissions) were regarded as samples associated with relapse. Samples which can be attributed to an intoxication were identified as described in the TDM-form. The serum level of clozapine, as well as age, gender, smoking habits, concurrent drugs, psychiatric diagnosis and dose of clozapine were evaluated. Data analysis was performed on individual samples and, alternatively, on multiple samples from a single patient which are summarized according to a typical clinical situation. RESULTS: 404 serum levels were measured in 86 patients. After exclusion of patients receiving acute treatment, 65 relevant clinical situations were identified in 50 patients: 12 relapses, 8 intoxications (a total of 20 situations with poor outcome) and 45 situations involving patients with good maintenance outcome. Samples involving relapse had serum levels of 198 +/- 211 ng/ml (10-624), intoxications had serum levels of 1,969 +/- 705 ng/ml (900-2,900) and those with good outcome had serum levels of 384 +/- 255 ng/ml (56-1,028) (mean +/- SD (range)). By means of sensitivity of receiver operating characteristic curves (ROC) a lower limit of the therapeutic window can be estimated at about 50-250 ng/ml and an upper limit at about 745-1,050 ng/ml. The frequencies of good and poor outcome were significantly different within and outside these ranges, e.g. chi2 = 11.8 and p < 0.001 for 250 to 745 ng/ml. Comparison of only good outcome and relapse provided a significant difference in the serum level of clozapine (Student's t-test p = 0.024). However, 67% of relapses were predicted in a model of logistic regression only if the variables serum level and concurrent treatment with other psychotropic drugs were included simultaneously as independent variables. Neither variable was able to predict relapse if used as a single variable in separate models. Finally, it was found that serum levels of clozapine were increased in women, in aged patients and in nonsmokers. CONCLUSIONS: It is tentatively concluded that serum levels of clozapine < 50 ng/ml are related to relapse irrespective of concurrent psychotropic drugs. In cases where there are no concurrent psychotropic drugs, serum levels of clozapine < 250 ng/ml are associated with relapse. The risk of relapse is low for serum levels of clozapine > 250 ng/ml irrespective of concurrent psychotropic drugs. The risk of intoxication is increased with serum levels > 750 ng/ml. The TDM of clozapine is recommended during maintenance treatment.

Adult↗
PubMed2002

Absorption kinetics of paracetamol are not influenced by high anxiety levels in preoperative patients.

OBJECTIVE: If the absorption kinetics of orally administered drugs in preoperative patients are influenced by high anxiety levels as maintained by Simpson and Stakes [1987], then this aspect would have to be taken into consideration in the preparation for surgery and would make dose adjustments necessary in such patients. METHODS: We differentiated and quantified the anxiety level in 40 patients, 4 - 5 hours prior to an operation, using the State-Trait Anxiety Inventory (STAI). Subsequently, all patients were given 1000 mg of paracetamol and serum levels were analyzed by means of HPLC. RESULTS: Over the first 3 hours after application there were no significant differences in the parameters C(max) and t(max) between patients with high levels of anxiety and patients with low levels of anxiety. However, AUC (area under curve) values were slightly higher in patients with high levels of anxiety. CONCLUSIONS: No clinically relevant differences in absorption parameters were observed in patients with high and low levels of anxiety.

Acetaminophen↗
PubMed2001

Serum levels of amitriptyline and therapeutic effect in non-delusional moderately to severely depressed in-patients: a therapeutic window relationship.

In a prospective, open clinical study, the relationship between serum levels of amitriptyline (At) and nortriptyline (Nt) and the therapeutic effect after 6 weeks of treatment was investigated. Serum levels were measured by gas-liquid chromatography and the therapeutic effect was assessed by the Hamilton Depression Rating Scale (HAMD) and the Clinical Global Impression Scale (CGI). A number of 25 non-delusional, moderate to severely depressed inpatients were included. A therapeutic window relationship was detected by means of regression analysis (quadratic model). Low and high serum levels were associated with low therapeutic effect. In an intermediate range, the probability of good therapeutic effect was increased. This relationship reached significance for the serum levels of At (p < 0.05) and a trend for the sum of serum levels of At and Nt (p < 0.1). As expressed by the regression coefficient r2, about 25% to 35% of the variability of therapeutic effect was explained by serum levels. Dichotomized data sets according to limits of final values of HAMD and CGI as well as limits of a therapeutic window of 70 ng/ml and 200 ng/ml (sum of At and Nt) revealed significant differences by means of Fisher's exact test (p < 0.05). Furthermore, increased ratios of serum level of Nt per serum level of At were found to be associated with decreased therapeutic effect. Thus, the present data support the existence of a therapeutic window of serum levels of At in depression. Also taking into account other reports, this therapeutic window can be defined as being between about 70 and 220 ng/ml. The assay of serum levels of At can be used to lower the risk of unsatisfactory therapeutic outcome.

Adult↗
PubMed2001

The effect of anxiety and personality on the pharmacokinetics of oral midazolam.

UNLABELLED: We investigated the relationship between the pharmacokinetic variables of oral midazolam and patients' state/trait anxiety and personality. Twenty-six patients received the standard 15-mg oral dose for anxiolysis on the evening before otorhinolaryngological surgery. Blood samples were taken over a 9-h period after the administration, and the samples were analyzed for concentrations of midazolam and its two main metabolites by using a gas chromatography-mass spectrometry procedure. The pharmacokinetic variables maximum concentration, time to reach the maximum concentration, the elimination half-life, and the area under the curve were calculated from these data. When the patients were divided into groups with respect to their anxiety and personality scores, no significant differences in the pharmacokinetic variables of midazolam could be found. Only small, insignificant changes in the maximum concentrations were found with respect to nervousness and emotionality. We conclude that personality traits and anxiety levels had no effect on the pharmacokinetic variables of midazolam. IMPLICATIONS: We conclude that personality traits and anxiety levels had no effect on the pharmacokinetic variables of midazolam. Therefore, it is not necessary to obtain anxiety or personality scores to find the proper midazolam dose for the individual patient.

Administration, Oral↗
PubMed2001

Psycho- and immunopharmacological factors relevant to selection of volunteers in clinical studies.

There are many well-known factors and variables which play a role in the evaluation of pharmacokinetic and pharmacodynamic results gained from healthy volunteers. The genetic constitution is influenced by age, sex, circadian and seasonal variations, dietary factors, immunological function, alcohol intake, smoking, etc. Vesell repeatedly pointed out these facts some time ago [Vesell 1982, Vesell and Passananti 1977]. Since Janke [1964], we have suspected that personality traits can also influence the drug response. The following overview is dedicated to this field designated as differential psychopharmacology which, from the point of view ofthe author, has been given too little attention by pharmacologists and clinical pharmacologists. It has been demonstrated that the effect of psychotropic drugs, including placebo, can be differentially influenced by personality traits, e.g. introversion/extroversion, high level neuroticism/low level neuroticism and success motivation/failure motivation. For example, relatively high doses of diazepam (0.3 mg/kg), when compared to placebo, only impaired the psychophysical performance of extroverted volunteers whereas introverted volunteers remained unaffected. Pharmacokinetic parameters, e.g. absorption, biotransformation, can also be affected by the level of neuroticism or by anxiety, as demonstrated for diazepam, caffeine, paracetamol and theophylline. The absorption kinetics of diazepam and caffeine clearly differ between volunteers with high neuroticism scores and those with low neuroticism scores. Emotionally unstable volunteers absorbed the substances more quickly and more completely than emotionally stable volunteers. There were surprising differences in various immunological indices between dominant and submissive subjects. In dominant volunteers the immune system was more activated than in submissive volunteers. In the future, it will become increasingly necessary to obtain results for such target groups and to avoid generalized data, which may conceal the actual events. Differential clinical psycho-neuro-immunopharmacology may be an approach which is helpful in the development of "volunteer models" for clinical research in Phase I.

Adult↗
PubMed2000

The regional drug-therapy consultation service centre - a conception that has been serving patients and physicians alike for 30 years in Magdeburg (Germany).

OBJECTIVES: Thirty years ago, a drug therapy consultation service centre was established simultaneously with the Institute of Clinical Pharmacology based at the university hospital in Magdeburg. The combination of therapeutic drug monitoring and a drug information service including individual patient-oriented drug dosage and bedside consultation permits an effective support of the treatment of drug related therapeutic problems. Currently, the service offers drug monitoring for 161 drugs and additional 46 metabolites. METHODS AND DISCUSSION: In a representative 2-year period (1997-1998), drug monitoring was performed for 6293 patients, and 569 drug-related inquiries were answered. The main categories of required drug information were: pharmacokinetics/metabolism/analytical problems (38%), adverse drug reactions/drug safety (24%), therapeutic drug use/drug indication (21%) and pharmaceuticals (9%). Further activities of the institute refer to teaching of undergraduates, continuing education of local physicians in recent aspects of drug therapy, providing therapeutic bulletins and conducting supporting clinical studies.

Drug Information Services↗
PubMed2000

Reliability of symptom reports by healthy volunteers treated with placebo over several time periods.

In four test periods (medication-free control, three placebo periods with the suggestion randomised placebo or sedative or stimulant) 78 healthy medical students had to check off on a side-effect questionnaire those symptoms that they had experienced over the previous 72 h (adverse nondrug reactions). In the control period only 14 volunteers (18%) were without symptoms. In the course of 4 weeks this number doubled, and the number of symptoms complained decreased correspondingly, e.g. tiredness, headaches, muscle and joint pains etc. This development is relevant inasmuch as in phase-I studies the well-being of the volunteers is often monitored over protracted periods of time and perhaps decreasing interest or a decreasing motivation must be reckoned with. One or two rounds of tests present special situations, in any case, which cannot be reproduced. As the frequency of the symptoms complained of is modified by the personality structure, balanced groups must be formed for controlled studies. In Phase I trials it may sometimes be useful to characterize the volunteers psychologically.

Adult↗
PubMed2000

Influence of nanoparticles on the brain-to-serum distribution and the metabolism of valproic acid in mice.

The suitability of nanoparticles as a drug-carrier system for the antiepileptic valproic acid has been studied in mice. The aim of the study was to increase the brain-to-serum ratio of the drug to reduce dose-related side effects in the periphery. The influence of nanoparticles on the metabolism of valproic acid was also investigated. The serum kinetics and the brain tissue levels of valproic acid were not altered by administration with nanoparticles. However, the nanoparticles did inhibit the metabolic degradation of valproic acid via mitochondrial beta-oxidation but did not influence any other metabolic pathway. It can be concluded that nanoparticles loaded with valproic acid may help to reduce the toxic side effects of valproate therapy, not by reducing the therapeutically necessary dosage but by inhibition of formation of toxic metabolites. Using their ability to selectively block a pathway nanoparticles may serve as a tool to investigate the metabolic origin of metabolites and their contribution to therapeutic efficacy and side effects.

Animals↗