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Biomedical subjects

L F Gram

Publications and source records attributed to L F Gram.

At least 163 records · Page 9Linked to original sources
PubMed1981

Dose-dependent kinetics of imipramine in elderly patients.

In a group of elderly depressed patients treated with imipramine (50-200 mg/day), six patients had the dose changed after 1-3 weeks of treatment. In all cases an increased dose resulted in a considerably disproportional rise in the plasma level of the active metabolite desipramine. In a group of elderly depressed patients treated with nortriptyline (40-100 mg/day) the dose/plasma level ratio could be examined in 6 patients, and there was no tendency towards a disproportional rise in plasma level, when the dose was raised. Dose changes, thus, may result in unpredictable changes in plasma levels during imipramine treatment and therapy control by plasma level monitoring may be difficult in these patients. Additional treatment with perphenazine (8-16 mg/day) to patients on imipramine (N = 3) or nortriptyline (N = 2) caused a marked rise in drug levels for imipramine in particular affecting the desipramine levels.

Aged↗
PubMed1981

The Hamilton depression scale. Evaluation of objectivity using logistic models.

The consistency of the Hamilton Depression Scale (HDS) as a measure of the severity of depressive states has been examined when the scale was used weekly during a trial when imipramine. By use of logistic models (Rasch) the consistency of the HDS has been considered across patient-variables as age, sex, plasma levels of imipramine, and diagnosis. The results showed that the original 17-item HDS was without adequate consistency, i.e. the total score of the sample of items was no one-dimensional measure of depressive states. However, a melancholia subscale of the HDS contained items the total of which can be used to compare patients quantitatively, although in some part of the analysis one of these items showed ceiling effect. It was concluded that the melancholia subscale (containing the items depressed mood, guilt, work and interests, retardation, psychic anxiety, and general somatic symptoms) can form the basis for further improvements in the field of quantitative rating scales for depressive states.

Adult↗
PubMed1980

The WHO Depression Scale. Relationship to the Newcastle Scales.

The WHO (World Health Organization) Depression Scale is a new rating scale developed to evaluate the complete clinical history and description of depression. Items of the WHO scale were transformed to cover the items of the two Newcastle scales that are designed to differentiate between endogenous and non-endogenous depressions. In 98 depressed inpatients examined prior to antidepressive therapy only moderate agreement between scores transformed to the two Newcastle scales was found. Also the distribution patterns of the scores on the two scales were different. In patients classified as endogenous on one or both scales a significant relationship between plasma levels of imipramine or clomipramine and antidepressive effect was found. In patients classified on both scales as doubtful - or non-endogenous depressions - no such correlation could be identified. The initial severity of depression, as defined by the Hamilton Depression Scale, was the same in endogenous, doubtful and non-endogenous depression according to the scores transformed to the two Newcastle scales.

Adult↗
PubMed1979

d-Propoxyphene kinetics after single oral and intravenous doses in man.

d-Propoxyphene kinetics was studied in 8 healthy male subjects after single oral doses of d-propoxyphene at 65, 130, and 190 mg and after slow intravenous infusion of 65 mg. Total urinary excretion (7 days) indicated complete oral absorption but systemic availability was reduced corresponding to fist-pass elimination of 30% to 70%. There was linearity between oral dose and the corresponding area under the plasma concentration/time curve of d-propoxyphene and the metabolite norpropoxyphene. The kinetic measurements showed 2- to 3-fold interindividual variations: oral clearance, 1.3 to 3.6 1/min; systemic clearance, 0.6 to 1.2 1/min; apparent volume of distribution, 700 to 1,800 1; d-propoxyphene half-life (t1/2), 8 to 24 hr; and norpropoxyphene t1/2, 18 to 29 hr. There were pronounced intraindividual dose-dependent variations in oral clearance in some subjects. The intravenous concentration curves indicated a 3-compartment distribution model.

Administration, Oral↗
PubMed1977

Interaction of perphenazine with the kinetics of nortriptyline.

The kinetics of nortriptyline in four patients were investigated before and during treatment with perphenazine (24-36 mg/day) by administering 57 mg nortriptyline hydrochloride as an intravenous infusion and evaluating the resulting plasma concentration data according to a two compartment open model. In all patients an increased biological half-life as well as a decreased systemic clearance and rate of metabolism were found in the perphenazine-period, thus confirming the inhibitory effect of perphenazine on the metabolism of nortriptyline found in earlier studies. Some interaction with distribution parameters was also indicated, but on the whole the model parameters did not provide much further information about the interaction. Although the most pronounced changes were found with the patient getting the highest dose of perphenazine, the dose-effect relationship remains obscure.

Dose-Response Relationship, Drug↗
PubMed1976

Comparison of single dose kinetics of imipramine, nortriptyline and antipyrine in man.

The single dose kinetics of imipramine (IP), nortriptyline (NT), and antipyrine (AP) were compared in 7 healthy subjects. Test doses of AP were given intravenously and test doses of IP and NT were given both orally and by intravenous infusion. The plasma concentration/time curves after intravenous IP and NT were analysed according to a 2-compartment open model. In addition a blood flow independent 'true' clearance was calculated according to a sinusoidal perfusion model. Indirect estimates of hepatic blood flow were obtained from the oral and i.v. plasma concentration/time curves after NT administration. Compared to NT, IP had statistically significant higher clearances, shorter half-lives, and smaller apparent volumes of distribution. There was a significant correlation between apparent volume of distribution (Vdbeta) of IP and NT (n = 5, r = 0.85), but only a weak correlation between the clearance measurements of the two compounds. Systemic clearance of AP and IP showed some positive correlation (n = 7, r = 0.73), whereas there were no significant correlations between AP and NT kinetics. The data indicate that inter- and intraindividual variations in hepatic blood flow may influence the measurements. Other possible sources of variability are individual differences in hepatic extraction kinetics, and differences in binding to blood constituents.

Administration, Oral↗
PubMed1976

Plasma levels and antidepressive effect of imipramine.

The relationship between the antidepressive effect of imipramine and the plasma concentrations of imipramine and the active metabolite desipramine was studied in 24 patients suffering from endogenous depression. After a placebo period of 7 days, the patients received imipramine, 75 mg 3 times a day. The dose was reduced in patients with pronounced side effects. Blood samples for drug assay were drawn in the morning, 15 hr after the last drug intake. Imipramine and desipramine in plasma were assayed by quantitative in situ thin-layer chromatography. Individual variations in plasma concentration were 20- to 30-fold in both imipramine and desipramine. Severity of depression was assessed on the Hamilton Rating Scale (HRS). Eleven of 12 patients who responded satisfactorily to the treatment (HRS post-treatment score less than 8) had plasma concentration of imipramine greater than or equal to 45 mug/L, and desipramine greater than 75 mug/L, whereas the 12 patients not responding satisfactorily (post-treatment score on HRS greater than or equal to 8) all had concentrations of imipramine or desipramine or both below these limits.

Adult↗
PubMed1975

Kinetics of nortriptyline in man according to a two compartment model.

Plasma concentrations of nortriptyline have been assayed in four subjects after intravenous infusion of 57 mg nortriptyline hydrochloride. The data were evaluated according to a two compartment open model. The calculated best-fitting curves were in good agreement with the experimental data, better than could be expected from a simpler model. This justifies the assumption that the kinetics of nortriptyline in man may be described by this model with an appropriate input function. The data permitted estimation of all the parameters of the model. The meaning of the parameters is discussed, particularly in relation to individual variation.

Adult↗