Search PubMed⌕ Search

Biomedical subjects

S Dawling

Publications and source records attributed to S Dawling.

72 records · Page 4Linked to original sources
PubMed1980

The prediction of tricyclic antidepressant plasma concentrations.

It is possible to predict steady-state plasma nortriptyline concentrations from pharmacokinetic data obtained after giving a single oral dose. The best pharmacokinetic predictor was found to be intrinsic clearance, although simpler kinetic criteria such as the 24, 48, or 72 hour plasma concentration were almost equally valuable. Use of such a tolerance test is a simple yet powerful way of obtaining advance information on individual differences in drug disposition. From such kowledge it should be possible to individualize drug dosage regimes so as to maximize antidepressant action, while at the same time minimizing the risk of toxicity. This test could be applied routinely in the psychiatric care of both inpatients and outpatients.

Depression↗
PubMed1980

Single oral dose pharmacokinetics of clomipramine in depressed patients.

The pharmacokinetics of a single oral dose of clomipramine were examined in a group of depressed patients, 8 female and 2 male with a mean age of 51 years (range 21-78). Their mean clomipramine half-life was 36 hours and mean plasma clomipramine clearance 73 litres per hour, with a wide range in each case. These results differ from those previously reported in volunteer subjects, who had shorter clomipramine half-lives. Pharmacokinetic studies should therefore be performed in patients undergoing treatment, rather than healthy volunteers.

Administration, Oral↗
PubMed1980

Plasma concentration of clomipramine and desmethylclomipramine and clinical response in depressed patients.

In the treatment of endogenous depression with tricyclic antidepressants, poor response has been reported to be associated with both high and low plasma levels of drug. To clarify any such relationship, plasma levels of clomipramine and its metabolite desmethylclomipramine have been compared with clinical response in endogenously depressed patients treated with 150 mg clomipramine nightly for up to six weeks. Although individuals varied considerably in the plasma drug levels attained, steady state was generally reached after two weeks, while desmethylclomipramine usually continued to accumulate in the plasma to higher levels than the parent compound. As measured by Hamilton rating scores, clinical response showed no correlation with plasma clomipramine concentrations, although poor response tended to be associated with low levels of drug and high levels of metabolite. The latter might explain why mean severity of depression and side effects appeared to increase between three and six weeks.

Adult↗
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

Simplified method for monitoring tricyclic antidepressant therapy using gas--liquid chromatography with nitrogen detection.

A simplified gas chromatographic method for the rapid measurement of tricyclic antidepressant drugs in plasma using a nitrogen-sensitive detector is described. All drugs are extracted and chromatographed under identical conditions. Tertiary amines are separated from their secondary amine metabolites, which are determined simultaneously without the need for derivatisation. The lower limit of accurate determination for most drugs is 10 microgram/1. The method has been applied to the routine measurement of amitriptyline and nortriptyline in plasma from patients receiving antidepressant treatment. Large and important interindividual differences in plasma concentrations in the patients investigated have been found, and the significance of these results is discussed.

Antidepressive Agents, Tricyclic↗
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↗
PubMed1978

Measurement of plasma nortriptyline concentrations: radioimmunoassay and gas-chromatography compared.

We compared measurement of plasma nortriptyline by a recently developed radioimmunoassay technique with values obtained by traditional gas chromatography. The coefficient of correlation (r) was 0.98 for 84 samples from 21 controlled patients; for a separate series of 45 samples from 34 patients who were receiving in addition other medication, r was 0.96. Use of radioimmunoassay in the routine determination of plasma nortriptyline concentration is discussed.

Chromatography, Gas↗
PubMed1977

Effect of activated charcoal on absorption of nortriptyline.

The ability of 'Medicoal', a new effervescent, activated charcoal preparation, to adsorb nortriptyline, has been investigated both in vitro and in vivo. A single dose of the effervescent charcoal 30 min after a dose of 75 mg nortriptyline produced a 60% mean reduction in both peak plasma levels and nortriptyline availability in healthy volunteers. Multiple doses of the effervescent charcoal produced 70% mean reduction in peak nortriptyline levels and availabiltiy. Activated charcoal is recommended for the treatment of tricyclic antidepressant poisoning. In in-vitro tests, a 10 g packet of the effervescent preparation containing 5 g activated charcoal) had an adsorptive capacity of approximately 3000 mg nortriptyline, a dose not usually exceeded in most cases of trycyclic antidepressant overdose.

Absorption↗
PubMedDate not supplied

Comparison of the effect of amitriptyline in standard and sustained-release formulations on cardiac systolic time intervals.

Eight healthy male volunteers were given single doses of 75 mg standard and sustained-release amitriptyline in a double-blind, crossover trial. Systolic time intervals (STI) were measured hourly on drug and base-line days. Plasma amitriptyline and nortriptyline were measured hourly on drug days. To correct for diurnal variations, STI values on drug days were compared with values of base-line days at the same hour. Both formulations of amitriptyline produced initial decreases in heart rate (followed by a return to normal values) and a significant decrease in ventricular electrical systole (QTc), which began before plasma amitriptyline could be detected. One of the eight volunteers showed T wave depression following amitriptyline. The preejection period (PEPc) increased significantly in three of the eight volunteers (max 19%), and this change was due to an increase in true isovolumetric contraction time (TICT). The left ventricular ejection time (LVETc) decreased significantly in all volunteers (5%, p less than 0.001), the change being greater after sustained-release amitriptyline. Standard amitriptyline produced larger changes than sustained-release amitriptyline in QTc and PEPc. The overall increase in the PEP/LVET ratio, indicating an impairment of cardiac function, was twice as large after standard than after sustained-release amitriptyline (38% and 16%, respectively). The possible mechanisms of cardiac effects of amitriptyline are discussed. Our findings indicate that a sustained-release preparation may be safer than a standard preparation of amitriptyline, particularly if there is a risk of cardiac complications.

Adult↗
PubMedDate not supplied

Dosage adjustment from simple nortriptyline spot level predictor tests in depressed patients.

20 routine patients with endogenous depression were investigated in a kinetic and 4 week treatment study. Steady-state plasma nortriptyline concentrations above 200 microgram/L were associated with a highly significant poorer therapeutic outcome. The correlations between the 24, 48 and 72 hour concentrations and steady-state concentration were very good (r = 0.81, 0.97, 0.94; p less than 0.0001) and better than the correlation between half-life and steady-state (r = 0.65; p less than 0.01). The Spearman rank correlations (Rs) between amelioration of depression measured by the Hamilton Rating Scale (HRS) and the 24, 48 and 72 hour concentrations were highly significant (Rs = 0.74, 0.79, 0.79; p less than 0.001) but for half-life (Rs = 0.33) the correlation was not significant. The single 48 hour plasma nortriptyline concentration following a single oral dose is recommended as a reliable simplified monitoring test suitable for a busy clinic. The test is useful for dosage adjustment to maximise antidepressant action and minimise toxicity. A tentative dosage adjustment schedule for individualising antidepressant treatment with nortriptyline based on the 48 hour or the 24 hour plasma concentration is proposed.

Clinical Trials as Topic↗
PubMedDate not supplied

Pharmacokinetics of single oral doses of nortriptyline in depressed elderly hospital patients and young healthy volunteers.

A single oral dose of 75mg nortriptyline was given to a group of 20 depressed elderly patients in hospital. Subsequent plasma nortriptyline concentrations were used to calculate the half-life and clearance of the drug. These measurements were compared with those made previously in 17 healthy young volunteer subjects. Plasma nortriptyline half-life was longer and clearance slower (p < 0.002) in the elderly group than in the volunteers. There was no correlation of age with either of these parameters within the 2 groups, and no differences in nortriptyline pharmacokinetics could be detected between the male and female volunteer subjects. The possible reasons for these findings and their clinical consequences are discussed.

Administration, Oral↗
PubMedDate not supplied

Amitriptyline dosage prediction in elderly patients from plasma concentration at 24 hours after a single 100mg dose.

Fifteen depressed elderly patients (14 female, 1 male; mean age 85 years) received a single oral dose of amitriptyline. The concentration of amitriptyline plus nortriptyline in a blood sample taken 24 hours later was used to predict by means of a nomogram the amitriptyline dosage required for each patient. Each dose was selected to produce steady-state amitriptyline plus nortriptyline concentrations close to 140 micrograms/L. The daily dosage ranged from 20 to 100mg (mean 62mg). Patients received the individually calculated dose each night, and weekly blood samples were obtained for drug analysis. At 2 weeks, mean amitriptyline plus nortriptyline concentrations were 118 +/- 21 micrograms/L. Eight of the patients were studied for a further 2 weeks and the mean amitriptyline plus nortriptyline concentration was then 111 +/- 19 micrograms/L. The dose prediction test is easy to use and ensures each patient receives an adequate but safer dose of amitriptyline than might otherwise be prescribed routinely.

Aged↗