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Biomedical subjects

R Braithwaite

Publications and source records attributed to R Braithwaite.

14 recordsLinked to original sources
PubMed1979

The role of plasma level monitoring of tricyclic antidepressant drugs as an aid to treatment.

Use of the tricyclic antidepressant drugs is the most common pharmacotherapeutic approach to the treatment of depression. It is a common clinical experience to find that a fair proportion of patients fail to show a satisfactory response and that others complain of side-effects. Important factors which influence this situation are the diagnostic criteria used to select patients for drug treatment, the dosage prescribed and individual compliance. Measurement of plasma drug concentrations has been proposed as a more rational way of increasing the efficacy of antidepressant medication and avoiding toxicity. A number of studies have shown a correlation between plasma concentrations of these drugs and clinical effects, but the relationship is far from simple. With amitriptyline and nortriptyline there is good evidence for a 'therapeutic window' within which maximum antidepressant action is obtained. Many patients being treated with these drugs have plasma levels outside recommended therapeutic ranges. Experience in our department has shown that there are a number of clinical situations where routine plasma level monitoring of selected antidepressants is of value: (1) inadequate clinical response; (2) side-effects/toxicity; (3) complicating medical conditions; (4) suspected poor compliance; and (5) long-term therapy. Such measurements are a relatively simple and inexpensive way of maximizing the benefits of drug therapy and a means of tailoring drug dosages to suit individual requirements.

Aged↗
PubMed1979

Techniques for plasma protein binding of demethylchlorimipramine.

The cerebrospinal fluid (CSF) and plasma levels of demethylchlorimipramine (DMCI) were determined during treatment of depression or obsessive-compulsive disorders with chlorimipramine. In 18 patients the mean CSF/plasma ratio of DMCI was 2.6% +/- 0.7 SD with fourfold variation (1.1% to 4.0%). In spite of this variation, the levels in CSF and plasma at steady state correlated closely (r = 0.91; p less than 0.001). With equilibrium dialysis for the determination of the protein binding of DMCI, a much higher free fraction was found in patients (8.0 +/- 1.6%) and in control subjects (8.2 +/- 1.4%). It was shown that part of the plasma binding capacity was lost during the incubation. Results obtained by ultrafiltration (3.9 +/- 1.0% unbound drug) were closer to the in vivo results, but this method also had disadvantages; much of the drug was absorbed on the ultrafiltration dialysis membrane. Our results suggest that there is a need for care in the selection of a technique for studies of drug protein binding.

Blood Proteins↗
PubMed1978

Effect of delayed administration of activated charcoal on nortriptyline absorption.

Activated charcoal is known to reduce the absorption of therapeutic doses of nortriptyline in vivo when administered 30 min after drug ingestion. In a group of volunteers, one sachet (10 g) of a new activated charcoal preparation, 'Medicoal' was found to produce a highly significant reduction in nortriptyline absorption when given as long as four hours after nortriptyline dosing. Activated charcoal may therefore be useful in the treatment of tricyclic antidepressant poisoning even if a delay of several hours ensues before medical help is sought.

Adult↗
PubMed1978

Ion-pair liquid chromatography of amitriptyline and metabolites in plasma.

A method is described for the determination of amitriptyline and nortriptyline in the plasma of patients during treatment. The method is based on liquid chromatography of the amines as ion-pairs with perchlorate. The separation column is packed with silica gel, and a mixture of diisopropyl ether, dichloromethane, methanol and water containing the counter ion is used as eluent. High efficacy and stability of the system is achieved. The separation of metabolites is demonstrated. The cis- and trans-10-hydroxy isomers of amitriptyline and nortriptyline are easily resolved with this chromatographic system.

Amitriptyline↗
PubMed1978

High plasma nortriptyline levels in the treatment of depression. I.

Following a 3-day single-dose kinetic study, 21 moderate to severely depressed inpatients were treated with 100 mg of nortriptyline nightly. Eighteen patients completed the 4-wk trial. The severity of depression was measured by weekly Hamilton Rating Scale and global rating. Blood for plasma nortriptyline estimation was taken at weekly intervals 12 h following the nighttime dose. There was a 6-fold variation in mean plasma nortriptyline levels, ranging from 120 microgram/L to 681 microgram/L. Patients with high plasma levels (greater than 200 microgram/L) showed significantly poorer clinical responses than those with levels in routine treatment, high plasma nortriptyline levels are significantly less effective than intermediate levels. Single-dose pharmacokinetic data obtained on the same patients showed a highly significant correlation with mean steady-state plasma levels obtained, which themselves correlated with clinical response. The value of predicting high plasma nortriptyline levels which are associated with poor response is discussed.

Adult↗