Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toremifene is a triphenylethylene derivative structurally and pharmacologically similar to tamoxifen. This Phase I trial assessed the safety, pharmacokinetics, anti-estrogenic, and estrogenic effects of toremifene at six dose levels (10, 20, 40, 60, 200, and 400 mg/day). The most common side-effects associated with therapy included gastrointestinal (nausea/vomiting 43%), anti-estrogenic (hot flashes 29%), and CNS (dizziness/vertigo 12%). Three patients with bone metastases from breast cancer developed hypercalcemia. At doses greater than or equal to 40 mg/day a decline in LH and FSH occurred which was not statistically significant. At all doses tested SHBG rose during therapy. A dose dependent estrogenic blockade was seen on the vaginal epithelium following challenge with transdermal estradiol. Steady-state concentrations of toremifene were reached within 4 weeks, and at doses greater than or equal to 60 mg/day ranged from 879-3445 ng/ml. The half-life was found to be 5 days, and at three weeks following discontinuation of treatment concentrations greater than 24 ng/ml were detected. The N-desmethyl and 4-hydroxy metabolites achieved steady state levels within 4 weeks and had half-lives of 6 and 5 days respectively. Partial responses were seen in 4 patients, 3 with breast cancer treated at 200 mg/day and 1 with endometrial cancer treated at 400 mg/day.
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PMID:Phase I study of the tolerance and pharmacokinetics of toremifene in patients with cancer. 214 80

A double-blind cross-over study with Org OD 14 and placebo was performed in 82 menopausal patients presenting with hot flushes and associated symptoms. Patients were randomly allocated to Org OD 14 or placebo as first treatment, and switched to placebo or Org OD 14 as second treatment. Each treatment period lasted for 16 weeks; no wash-out period was introduced. Tablets containing 2.5 mg of Org OD 14 or matched placebo tablets were supplied. Data on the following variables were obtained and analysed by the non-parametric randomization test for paired observations: hot flushes, sweating, dizziness, palpitations, fatiguability, headache, sleeplessness, irritability, breathlessness, backache and loss of libido and, in 16 patients, on circulating levels of FSH, LH, PRL, T3, T4, cortisol (F), SHBG, TBG and CBG. Twenty patients (13 placebo, 7 Org OD 14) withdrew, because their symptoms did not improve and one patient withdrew for reasons unrelated to treatment, so that 61 patients completed the study. The data demonstrated a good clinical effect and statistically significant differences in favour of Org OD 14 for hot flushes and a number of associated symptoms. Many patients reported on a general feeling of well being and a mood-elevating effect following Org OD 14. Org OD 14 significantly suppressed FSH and LH levels, while those of PRL remained unchanged. Although there was slight suppression of TBG and T4 which attained statistical significance, there was no influence on the most important parameter, T3. SHBG levels were slightly suppressed, whereas F and CBG levels were unaffected.
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PMID:Placebo-controlled cross-over study of effects of Org OD 14 in menopausal women. 675 12