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Biomedical subjects

L F Gram

Publications and source records attributed to L F Gram.

At least 181 records · Page 10Linked to original sources
PubMed1975

First-pass metabolism of imipramine in man.

The systemic availability of orally administered imipramine (IP) varied from 29 to 77% in 4 subjects. The decrease in availability was due to an excess in metabolism after oral administration. This first-pass metabolism did not correlate with plasma half-life, apparent clearance, or the rate of metabolite excretion in urine. There was close correlation with the excess in formation of demethylated metabolites after oral administration, which suggests that the first-pass metabolism is mediated by demethylation, but does not correlate to the total rate of demethylation.

Administration, Oral↗
PubMed1975

First-pass metabolism of nortriptyline in man.

The kinetics of nortriptyline were studied after oral and intravenous (iv) administration of test doses of 50 mg 14C-nortriptyline. The systemic availability of orally administered nortriptyline varied from 0.46 to 0.59 in 6 subjects. The decrease in availability was due to metabolism after administration. Systemic clearance varied from 0.31 to 0.66 L/min. From these measurements indirect estimates of the hepatic blood flow could be made, and a variation from 0.6 to 1.5 L/min was found. Quantitative measurements of first-pass metabolism could also be obtained from urinary metabolite excretion data when the kinetics of metabolite formation and elimination were taken into account. From the second or third day after the test dose, the urinary excretion rate of total radioactivity declined monoexponentially with half-lives closely corresponding to the plasma half-lives of unchanged nortriptyline. Analysis of the data from the iv test according to a 2-compartment open model showed that there was a close correlation between the rate constant of distribution from central to peripheral compartment (k12) and the elimination rate constant in the central compartment (kel). Still, there was some variation in the kel/k12-ratio, and this variation corresponded to the variation of the estimated hepatic blood flow.

Administration, Oral↗
PubMed1975

Quantitative rating of depressive states.

A step-by-step analysis of Beck's and Hamilton's rating scales showed that both scales failed to differentiate adequately between moderate and severe depression measured by a global clinical assessment. Each item of the scales was tested for calibration, ascending monotonicity, and dispersion parallel to the clinical assessment. Twelve items of Beck's scale and six items of Hamilton's scale were found valid with respect to these criteria. Those items should be taken into account in future research for baseline ratings and for change ratings of depressive states quantitatively.

Adult↗
PubMed1975

Quantitative rating of manic states. Correlation between clinical assessment and Biegel's Objective Rating Scale.

We have investigated Biegel's manic-state rating scale and found the interrater reliability high when the scale was administered both by nurses and psychiatrists. In our study of validation, we tested each item of the scale for calibration, ascending monotonicity and dispersion parallel to a global clinical assessment of the manic state. Six of the scale items were then found valid and those items differed from the valid items in studies of Biegel by including increased social contact. Like Biegel, we found a positive correlation between items concerned with depressed mood, indicating a fluctuation in the mood of manic patients during 8 hours of observation.

Adult↗
PubMed1975

Effects of perphenazine on imipramine metabolism in man.

In previous studies we have shown that perphenazine inhibits the metabolism of nortriptyline and imipramine. In this study the metabolism of 14C-imipramine and 14C-desipramine was studied before and during treatment with perphenazine. Studies on the imipramine and desipramine metabolites in urine showed that the major effect of perphenazine is an inhibition of the 2-hydroxylation of imipramine and desipramine. This causes a decreased formation and excretion of non-conjugated and glucuronide bound hydroxy metabolites and accumulation of imipramine and desipramine. There was some relationship between the dose of perphenazine and the decrease in total urinary excretion but the individual variations in response were pronounced (2-3-fold).

Adult↗
PubMed1972

Drug interaction: inhibitory effect of neuroleptics on metabolism of tricyclic antidepressants in man.

Total urinary excretion of radioactivity after oral or intravenous administration of a test dose of (14)C-imipramine was measured in eight patients. They were tested before, during, and after treatment with neuroleptics. Excretion diminished while the patients were being treated with perphenazine, haloperidol, or chlorpromazine, though not during flupenthixol treatment.Total urinary excretion of radioactivity and plasma levels of metabolites and unchanged drug were measured in five patients after a test dose of (14)C-nortriptyline. Each patient was tested before and again during perphenazine treatment. In all patients perphenazine treatment caused: (1) decrease of total urinary excretion, (2) decreased plasma level of metabolites, and (3) increased plasma level of unchanged nortriptyline.These results indicate that neuroleptics inhibit the metabolism of tricyclic antidepressants in man.

Adult↗