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Biomedical subjects

R O Friedel

Publications and source records attributed to R O Friedel.

At least 55 records · Page 3Linked to original sources

Quantitation of biologically important primary amines as their isothiocyanate derivatives by gas chromatography using nitrogen detector and validation by selected ion monitoring.

A gas chromatographic method for the quantitation of biologically important primary amines using nitrogen detector is described. The primary amines are converted to their isothiocyanate derivatives by reaction with carbon disulfide. Appropriate non-biological primary amines are used as internal standards. The usefulness of the method is illustrated by analysis of biological samples, such as plasma, urine, cerebrospinal fluid and tissue samples and the results were validated using gas chromatography-mass spectrometry with selected ion monitoring.

Amphetamines↗

A comparison of plasma and serum levels of two tricyclic antidepressants: imipramine and desipramine.

This study was performed to determine the difference, if any, between serum and plasma levels of the tricyclic antidepressant drugs imipramine and desipramine. Serum and plasma samples were drawn simultaneously from patients taking either of these drugs. Statistical analysis indicated no difference in the drug levels; that is, serum and plasma levels were identical.

Blood Chemical Analysis↗

Quantitative mapping of metabolites of imipramine and desipramine in plasma samples by gas chromatographic-mass spectrometry.

Imipramine and desipramine are known to metabolize primarily by demethylation and hydroxylation. Hydroxy metabolites, 2-hydroxyimipramine and 2-hydroxydesipramine, are reported to be pharmacologically active by in vitro studies. We now report a simple gas chromatographic-mass spectrometric selected ion-monitoring (SIM) method for hydroxy metabolites of imipramine and desipramine from plasma samples using deuterated analogues as internal standards. d4-Internal standards for imipramine, desipramine, and their 2-hydroxy derivatives, were prepared in our laboratory and added to plasma samples, extracted at pH 9 with ethyl acetate, then at pH greater than 11 with hexane-isopropanol. The extracts were combined and evaporated under nitrogen. The trifluoroacetyl derivatives were prepared using N-methyl-bis-trifluoroacetamide and analyses were performed using GC-MS selected ion-monitoring in the electron ionization mode. Hydroxylation to 2-hydroxy metabolites varied widely between subjects. We also noticed in vivo methylation of desipramine to imipramine as a pathway of its metabolism in 15% of the subjects. It is suggested that plasma levels of all active metabolites must be considered in the assessment of the relationship of plasma levels of the drug to clinical response.

Biotransformation↗

Electrocardiogram changes and plasma desipramine levels during treatment of depression.

Twenty-six symptomatic subjects who met research diagnostic criteria for major affective disorder and were free of cardiovascular disease were treated for 3 wk with a fixed dosage schedule of desipramine (DMI) to a maximum of 200 mg/day. An electrocardiogram (ECG) and DMI plasma level determinations were obtained before treatment and weekly thereafter. DMI levels during the trial ranged from 13.4 to 882.2 ng/ml. DMI treatment was associated with increase in heart rate (p less than 0.001), prolongation of the PR (p less than 0.001), QRS (p less than 0.001), and QTc intervals (p less than 0.001), and increase in T wave amplitude (p less than 0.001). Significant (p less than 0.001) but relatively weak correlations were noted between DMI plasma levels and heart rate (r = 0.405), QRS interval (r = 0.346), QTc interval (r = 0.534), and T wave amplitude (r = -0.386). PR interval prolongation was independent of DMI levels (r = 0.171). DMI treatment induced no clinically significant ECG alterations or cardiovascular adverse effects. The relevance of DMI plasma level and the possible roles of other contributing factors in the production of these ECG changes are discussed.

Adult↗

Low-dose neuroleptic regimens in the treatment of borderline patients.

The use of pharmacologic agents in treating patients described as borderline generally has been accorded an insignificant, or at best, minor, role. We discuss this observation and review the literature that has dealt with this aspect of treatment. Diagnostic criteria are presented that appear to define a specific population of borderline patients who have been observed to be responsive to low doses of neuroleptic drugs. Five case histories of patients with conditions diagnosed and treated in this manner are presented, followed by a discussion of the implications of this approach in terms of clarifying the nosologic issues that have arisen around the "borderline" concept.

Adult↗

Relationship of plasma levels of chlordiazepoxide and metabolites to clinical response.

The authors report on the relationship between the antianxiety effects of chronically administered chlordiazepoxide (CDX) and plasma levels of CDX and two of its metabolites, desmethylchlordiazepoxide (DMCDX) and demoxepam (DMX). Fifteen subjects with moderate to severe anxiety were studied in a double-blind, placebo-controlled, crossover design. Significant correlations were found between anxiety reduction and DMCDX and DMX plasma levels. No such correlation was observed between anxiety reduction and CDX levels. These data suggest that in chronically treated subjects, DMCDX and DMX have significant antianxiety properties which surpass those of CDX itself.

Adult↗

Analysis of tricyclic antidepressants in human plasma by GLC--chemical-ionization mass spectrometry with selected ion monitoring.

A method is described for the analysis of amitriptyline, doxepin, imipramine, nortriptyline, desmethyldoxepin, desipramine, and protriptyline in human plasma utlizing GLC-chemical-ionization mass spectrometry with selected ion monitoring. The assay is highly specific and is quantitative to at least 1 ng/ml with a standard error typically less than 5%. Representative concentrations of the parent compounds and their monodemethylated metabolites, as meeasured in plasma samples from patients under treatment with tertiary amine tricyclic antidepressants, are given.

Antidepressive Agents, Tricyclic↗

Subtypes of depression--diagnosis and medical management.

Depression is both a common and a greatly undertreated illness in the United States today. The focus of this review is a definition of the characteristics of four subtypes of depression which appear to be differentially sensitive to four different classes of medications. The tricyclic antidepressants should be used for patients with unipolar depression and vegetative symptoms. Lithium appears to be most effective for bipolar depressives. The monoamine oxidase (MAO) inhibitors are best used for patients with atypical depression. Antipsychotic medications appear to be useful for depressed patients with psychotic symptoms or agitation. Recent pharmacokinetic and biochemical data, including serum lithium levels, plasma tricyclic levels, and the predictive ability of pretreatment urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) levels are also reviewed.

Adolescent↗