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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
PubMed1995

Megabore capillary gas-liquid chromatographic method with nitrogen-phosphorus selective detection for the assay of haloperidol and reduced haloperidol in serum: results of therapeutic drug-monitoring during acute therapy of eight schizophrenics.

A gas chromatographic method using a HP-5 megabore capillary and nitrogen-phosphorus selective detection for the quantitative analysis of haloperidol (H) and reduced haloperidol (RH) in human serum or plasma is described. A 3-step liquid-liquid extraction is applied. The extraction yield of this procedure is 63% for haloperidol at 20 ng/ml. The limits of detection are 0.4 ng/ml for haloperidol and 1.0 ng/ml for the metabolite if 2 ml of body fluid are applied. At 10 ng/ml the within-day precision is 4.5% for H and 8.3% for RH. Serum levels of eight schizophrenic patients have been monitored weekly over a therapeutic period of six weeks. Seven patients mainly had metabolite ratios RH/H < 1 over the entire period of investigation. They exhibited a linear correlation between dose and serum concentration of haloperidol. In contrast, one patient had metabolite ratios RH/H > 1 over the entire period of the study. Due to considerable increased serum concentrations this patient did not show a linear correlation between the dose and the serum level of haloperidol.

Adult↗
PubMed1995

The healthy volunteer in clinical pharmacology: personality and motivation.

The aim of the present study was to quantify the personality structure and motivation of medical students, who are often the most readily available source of healthy volunteers, since it has long been known that the pharmacodynamics and pharmacokinetics of drugs can be substantially modified by predominant personality traits (e.g. neuroticism, extraversion). Over the course of 4 years, a total of 337 subjects (165 males, 172 females) out of the 496 medical students asked, participated in the study after appropriate instruction. Students were tested using the Motivation Q-Sort method which, by means of questions ("questionnaire sort"), investigates whether a subject tends to react in a success-motivated (SM) or a failure-motivated (FM) mode. The variable measured is the so-called net hope (NH), where NH > 1.6 corresponds to SM and NH < -0.3 corresponds to FM. We also used the Freiburg Personality Inventory (FPI) as a suitable method of determining personality structure. The predominant traits of interest found were nervousness (FPI 1), extraversion (FPI E), and neuroticism (FPI N). In the first series of tests (primary selection), motivation only was determined in 337 volunteers. The range was fairly broad, with NH values from 4.32 (highly SM) to -3.09 (highly FM). In the second series of tests, about 60 SM and 60 FM subjects were selected. The Motivation Q-Sort method was repeated with students placed under more difficult conditions, and the FPI was also performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Influence of endogenous and exogenous effectors on the pharmacokinetics of theophylline. Focus on biotransformation.

Theophylline has been widely used as a bronchodilatory drug for the treatment of neonatal apnoea in premature newborns and patients with obstructive airways disease. The development of analytical equipment and procedures to determine the systemic concentration of theophylline renders it possible to improve the effectiveness of theophylline therapy and reduce the incidence of toxic and adverse effects. Since the beginning of the 1970s, endogenous and exogenous factors (e.g. age, blood pH, concomitant diseases and drug therapy, meal preparation procedure, nutritional habits, pregnancy, gender, smoking and, to a lesser extent, biorhythms), influencing nearly all parameters of theophylline pharmacokinetics have been described. Drug absorption depends on galenic formulation, drug delivery, nutritional habits and the chemical derivatives used. The mean plasma protein binding rates depend on the method of plasma protein determination: acidic blood pH values and advanced age may result in reduced plasma proteins. The volume of distribution depends primarily on age; it is 2-fold greater in newborns than in adults. Furthermore, changes in blood pH values, the plasma protein content and the administration of concomitant drugs may vary this parameter. Biotransformation is the most clinically important pharmacokinetic parameter. Hepatic metabolism accounts for 90% of the metabolism of theophylline. Essentially, 2 microsomal isoenzymes of the cytochrome P450 system appear to be responsible for the N-methylation and 8-hydroxylation of the drug. Age and concomitant disease are the major endogenous effectors influencing biotransformation of theophylline, whereas biorhythms, gender and pregnancy are of lesser importance. Exogenous factors, such as concomitantly administered drugs, smoking and nutritional factors, affect biotransformation by inducing or inhibiting the metabolising enzymes. Because of intra- and interindividual variability in the pharmacokinetics of theophylline, which may be increased by the presence of endogenous and/or exogenous effectors, it is necessary to supervise theophylline therapy by therapeutic drug monitoring if target concentrations are to be achieved.

Absorption↗
PubMed1995

[The effect of valproic acid monotherapy on behavior and cognitive performance of children with idiopathic generalized epilepsy].

Valproic acid (VPA) currently plays an important role in the treatment of several different types of epilepsy. Especially in children and adolescents, VPA is used because of a minimum of adverse effects and generally little impact on cognitive and psychomotor functions. However, reports in the literature regarding the influence of VPA on behavior and cognitive performance and on EEG parameters vary widely. We investigated the effect of VPA monotherapy on behavioral components (attention, concentration, inhibitory control), cognitive efficiency (motor reaction time, learning, retention) and evoked potentials in 19 children aged 6 to 14 years with idiopathic generalized epilepsy and compared the results with those of healthy controls matched for age. In addition, we analyzed the serum levels of VPA and some of the VPA metabolites in all of the children with epilepsy immediately before the psychophysiological assessments. Our results show marked differences between the children with epilepsy and the healthy controls in all types of behavior and cognitive performance assessed. Abnormal behavior (disturbances of attention and concentration, impulsive behavior patterns) and significant changes in evoked potentials appear to be correlated with serum levels of VPA and certain VPA metabolites.

Adolescent↗
PubMed1995

[Special qualification of a photometric procedure for determination of salicylic acid in therapeutic drug monitoring].

A procedure for the determination of salicylic acid from human serum is presented. It is based on an acidic extraction, a basic reextraction and the detection of salicylic acid as its iron-III-complex by photometry. The procedure is quantitative over a wide range of linearity, easy to carry out and is especially suitable for therapeutic drug monitoring in the treatment of juvenile rheumatoid arthritis.

Arthritis, Juvenile↗
PubMed1994

Determination of nifedipine in human serum by gas chromatography-mass spectrometry: validation of the method and its use in bioavailability studies.

A procedure for the determination of nifedipine in human serum is described. The light-sensitive substance is isolated from serum by liquid-liquid extraction and analyzed using capillary gas chromatography with a mass-selective detector. The validation of the method shows that the extraction recovery is ca. 85%, the limit of detection is 2 ng/ml and the standard deviations of the intra-day precision test range from 5.8 to 7.4% with respect to the concentration. The procedure is highly selective and sensitive. It is especially suited for bioavailability studies because of its stability and high sampling rate.

Biological Availability↗
PubMed1994

Sensitive capillary gas chromatographic-mass spectrometric method for the therapeutic drug monitoring of valproic acid and seven of its metabolites in human serum. Application of the assay for a group of pediatric epileptics.

A sensitive capillary gas chromatographic-mass spectrometric method for the determination of valproic acid and 7 of its metabolites is described. It is based on the selected-ion monitoring of the tert.-butyldimethylsilyl derivatives using N-(tert.-butyldimethylsilyl)-N-methyl-trifluoracetamid (MTBSTFA) as the derivatization reagent. The limits of detection for valproic acid and its metabolites are in the low ng/ml-range, except for the 4-hydroxy metabolite with a limit of detection of 100 ng/ml. The method has been tested against an established GC method for valproic acid. The assay has been used for therapeutic drug monitoring in epileptic pediatric patients. The concentrations of the omega- and omega 1-oxidation metabolites in a group of patients receiving additional antiepileptic drugs were found to be significantly enhanced compared to the levels found in a monotherapy group.

Biotransformation↗
PubMed1994

Indicative therapeutic and toxic drug concentrations in plasma: a tabulation.

The table presented provides the therapeutic, toxic and lethal serum concentrations (to the extent demonstrable) of drugs. The use of plasma levels when administering drugs increases the likelihood of attaining a therapeutic response and serves to minimize the toxicity. The therapeutic range of agents should be used as a guideline and must be interpreted in conjunction with other monitoring parameters.

Adult↗
PubMed1993

[The bioequivalence of two nifedipine sustained-release formulations after single administration in steady state].

Investigations into the Bioequivalence of Two Nifedipine Controlled-release Formulations after Single Application and in Steady State. The bioequivalence of nifedipine (CAS 21829-25-4) in controlled-release formulation (Corinfar retard dragees) was tested versus a reference preparation in 22 subjects in a cross-over design after the first dose and in steady state. Compared to the reference, the preparations tested were found to have a relative bioavailability of 0.86 and 0.95, respectively. The bioavailability parameters of the preparations tested did not differ from each other. In particular, the fluctuation indices were noted to be highly similar. In view of the marked prolonged-action effect, a twice-per-day application is possible for the majority of the patients.

Adult↗
PubMed1992

Variability of serum levels for three oral 8-methoxypsoralen brands.

We conducted a pilot study to investigate the serum level patterns of 3 commercial and internationally introduced 8-methoxypsoralen (8-MOP) preparations in 9 patients for their bioequivalence and registered the interindividual variability of serum levels over 8 h after intake of 30 mg 8-MOP equivalent doses. On average, the highest serum levels (Cmax 120.1, range 235-61 ng.ml-1) were reached as early as 0.5-1 h after ingestion of Geroxalen soft gelatin capsules, whereas lower serum levels were seen after intake of the Oxsoralen hard gelatin capsules (Cmax 82.3, range 154-47 ng.ml-1) and the Mopsoralen tablets (Cmax 81.3, range 172-26 ng.ml-1). The importance of 8-MOP serum level determination for better and efficient PUVA therapy is discussed.

Adult↗
PubMed1992

[Do piroxicam and diclofenac impair reaction performance?].

The non-steroid agents diclofenac (1 mg/kg) and piroxicam (0.3 mg/kg) were studied for their performance-influencing effect in an acute placebo controlled cross-over trial involving 11 normal subjects in intraindividual comparison. Various cognitive tests (vigilance measurement, d2-test, concentration performance test), a determination test, and a flicker frequency test did not reveal verum effects when compared to placebo. In contrast, for subjects administered piroxicam, the self-state questionnaire according to Nitsch showed marked positive effects on the motivation and activation on the subjects. Numerical improvements (without being statistically significant) were also seen with respect to outgoingness and exertion increase. Moreover, subjects administered piroxicam were observed to be more concentrated and relaxed, whereas diclofenac exerted no influence on performance and the state of mind.

Adult↗
PubMed1991

Aquaculture disease and health management.

Disease problems constitute the largest single cause of economic losses in aquaculture. In 1988, channel catfish producers lost over 100 million fish worth nearly $11 million. Estimates for 1989 predict even higher losses. The trout industry reported 1988 losses of over 20 million fish worth over $2.5 million. No data are available on losses sustained by producers of shellfish. Bacterial infections constitute the most important source of disease problems in all the various types of production. Gram-negative bacteria cause epizootics in nearly all cultured species. Fungal diseases constitute the second most important source of losses, especially in the culture of crustaceans and salmon. External protozoan parasites are responsible for the loss of large numbers of fry and fingerling fin fishes and are a cause of epizootics among young shellfish. The number of therapeutants approved by the Food and Drug Administration is limited. Research to support the registration of promising therapeutic agents is urgently needed.

Animals↗
PubMed1991

[Side effects of nifedipine in healthy probands within the scope of a discontinued bioavailability study].

In a prematurely discontinued bioavailability study of 40 mg nifidepine retard dragees, it was shown in four subjects that cardiovascular side effects may occur at nifedipine levels equal to or higher than some 80 ng/ml serum. These cases were suggestive of a relationship between the areas under the concentration vs. time curves in the range of side effects, AUC (tC80), and the so-called side effects scores which were derived from the number and the duration of undesirable side effects.

Adult↗
PubMed1991

[Time course of inhibition of caffeine elimination in response to the oral depot contraceptive agent Deposiston. Hormonal contraceptives and caffeine elimination].

In the course of six months, the influence of the oral depot contraceptive, Deposiston (3 mg ethinylestradiol sulphonate and 10 mg norethisterone acetate per menstrual cycle) on the pharmacokinetics of caffeine as a model substance was studied in seven women in intraindividual comparison. The first examination began prior to administration of Deposition. The women were subjected to little challenge as saliva was used as the measuring compartment. Deposiston was found markedly delay the elimination half-life life of caffeine (p less than 0.05): t1/2 prior to therapy 4.9 +/- 2.6 h and, after as little as 2 mg ethinylestradiol sulphonate 8.0 +/- 3.5 h. In contrast to the effect observed for preparations containing less estrogen, these longer half-lives persisted throughout the trial. As expected, the AUC values were slightly elevated during this period, whereas clearance values were reduced.

Adult↗