Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aromatase inhibitor, 'pyridoglutethimide' (PyG), has been shown previously to suppress serum oestrogen levels in postmenopausal breast cancer patients and to achieve clinical responses at a dose of 500 mg twice daily (b.d.). This report gives the results of a detailed pharmacokinetic and endocrine study of PyG in ten patients. Four doses were tested at intervals of 2 weeks in the following order: 200 mg b.d., 400 mg b.d., 800 mg b.d., 1200 mg b.d. Concentration-time profiles of serum levels of PyG were curvilinear in all patients probably reflecting a saturation of metabolic enzymes. During repeat-dosing metabolism was enhanced approximately 2-fold. Plasma levels of oestradiol were significantly suppressed by the lowest dose of PyG. Although higher doses appeared to achieve greater suppression this was not statistically significant in this small group of patients. There were no significant effects at any dose on the serum levels of cortisol, aldosterone, luteinising hormone, follicle stimulating hormone, prolactin, sex hormone binding globulin or thyroid stimulating hormone. There was a dose-related increase in 17 alpha-hydroxyprogesterone levels and a dose-related decrease in levels of dehydroepiandrosterone sulphate (DHAS). The androgens DHA, testosterone and androstenedione also were significantly suppressed with at least one of the doses of PyG. Synacthen tests did not support these changes being a result of inhibition of 17,20 lyase. It is possible that they are due to enhanced clearance of DHAS. Two patients experienced no toxicity throughout the study, whilst a total of four patients were withdrawn because of side-effects: one at 400 mg b.d., two at 800 mg b.d., and one at 1200 mg b.d. The most frequent side-effects were nausea and lethargy. One patient showed an objective response to treatment.
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PMID:Endocrine, pharmacokinetic and clinical studies of the aromatase inhibitor 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione ('pyridoglutethimide') in postmenopausal breast cancer patients. 193 11

4-Hydroxyandrostenedione (4-OHA), a potent new aromatase inhibitor, was given i.m. (500-1000 mg) to 58 patients with advanced postmenopausal breast cancer. Of 52 assessable patients 14 responded (27%), in 10 (19%) the disease stabilized, and in 28 (54%) the disease progressed. Sterile abscesses occurred at the injection site in 6 patients and painful lumps were found in a further 3 patients. Two patients developed allergic-type reactions and 4 developed lethargy, suspected to be treatment induced. Plasma estradiol levels were suppressed from a mean of 7.2 +/- 0.8 (SE) pg/ml before treatment to 2.6 +/- 0.2, 2.7 +/- 0.2, and 2.8 +/- 0.3 pg/ml after 1, 2, and greater than 4 months, respectively, of treatment and remained suppressed in patients whose disease relapsed. No significant fall in estrone levels was seen. Similarly, dehydroepiandrosterone sulfate, sex hormone binding globulin, and gonadotrophin levels were unaltered after 6 months of treatment. Plasma 4-OHA levels were measured in a radioimmunoassay for androstenedione after chromatographic separation of 4-OHA from androstenedione. Drug concentrations ranged from 0.7 to 23.2 (7.8 +/- 1.1) ng/ml after 2 months on treatment. 4-OHA is an effective drug in the management of postmenopausal patients with breast cancer and does not produce notable systemic side effects.
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PMID:Treatment of advanced postmenopausal breast cancer with an aromatase inhibitor, 4-hydroxyandrostenedione: phase II report. 294 41

We reported the results of a randomized cross-over study comparing SH D 461 M (Climen) and Prempak-C in 38 postmenopausal women who were established users of hormone replacement therapy (HRT). Climen contains 11 tablets of 2 mg estradiol valerate (EV), and 10 tablets with 2 mg EV plus 1 mg of cyproterone acetate. Prempak-C, on the other hand, is a regime consisting of 28 tablets of 0.625 mg conjugated equine estrogens (CEE); the last 12 tablets are taken together with 0.15 mg of norgestrel (NG) tablets. Patients in Sequence I started with Climen for 6 months and then crossed-over to Prempak-C, for the next 6 months; patients in Sequence II, followed the reverse order. Following Climen treatment, significantly higher levels (P < 0.05, t-test) of sex hormone binding globulin (SHBG) and estradiol, when compared to Prempak-C treated subjects, were noted. No significant differences in follicle stimulating hormone (FSH), corticosteroid binding globulin (CBG), renin, angiotensinogen, angiotensin-I and aldosterone levels between the two treatment regimes were noted. While both regimes were effective in reducing menopausal symptoms, none of the regimes could eliminate all symptoms completely. Treatment with Climen appeared to result in less frequent occurrences of some symptoms. During periods of no estrogen (only true for Climen) as well as periods of maximum progestagen and estrogen (P and E), subjects on Climen had significantly lower incidence of some of the symptoms (backache, lack of concentration, lethargy and swelling) when compared to those on Prempak-C.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endocrine effects in Asian postmenopausal women treated with SH D 461 M and Prempak-C. 771 69

We reported the results of a randomized cross-over study comparing SH D 461 M (Climen) and Prempak-C in 38 postmenopausal women who were established users of hormone replacement therapy (HRT). Climen contains 11 tablets of 2 mg estradiol valerate (EV), and 10 tablets with 2 mg EV plus 1 mg of cyproterone acetate. Prempak-C, on the other hand, is a regimen consisting of 28 tablets of 0.625 mg conjugated equine estrogens (CEE); the last 12 tablets are taken together with 0.15 mg of norgestrel (NG) tablets. Patients in Sequence I started with Climen for 6 months and then crossed-over to Prempak-C, for the next 6 months. Patients in Sequence II followed the reverse order. Following Climen treatment, significantly higher levels (P < 0.05, t-test) of sex hormone binding globulin (SHBG) and estradiol, when compared to Prempak-C treated subjects, were noted. No significant differences in follicle stimulating hormone (FSH), corticosteroid binding globulin (CBG), renin angiotensinogen, angiotensin-I and aldosterone levels between the two treatment regimens were noted. While both regimens were effective in reducing menopausal symptoms, none of the regimens could eliminate all symptoms completely. Treatment with Climen appeared to result in less frequent occurrences of some symptoms. During periods of no estrogen (only true for Climen) as well as periods of maximum P and E, subjects on Climen had significantly lower incidence of some of the symptoms (backache, lack of concentration, lethargy and swelling) when compared to those on Prempak-C.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endocrine effects in Asian postmenopausal women, treated with SH D 461 M and Prempak-C. 773 78