Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042963 (vomiting)
 31,883 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

Toremifene (Fareston) is a triphenylethylene derivative structurally similar to tamoxifen (Nolvadex) that was selected for development based on its in vitro activity against breast cancer and its lesser uterotrophic effect than tamoxifen in rat models. In phase I and II studies conducted in several countries, toremifene was well tolerated over a wide range of doses (10 to 680 mg/d). The major side effects were hot flashes, nausea, and vomiting. Toremifene's excretion half-life is 5 days. It produces a modest decline in serum levels of luteinizing hormone, follicle-stimulating hormone, and antithrombin III, as well as an increase in sex hormone-binding globulin levels. In studies in which toremifene was used as first-line therapy in patients with estrogen receptor (ER)-positive or ER-unknown tumors, response rates to doses of 40 to 60 mg/day ranged from 30% to 54%. In two larger studies of patients who had proved refractory to tamoxifen therapy, toremifene produced an objective response rate of 4% to 5%. When patients with stable disease were added to those with objective responses, 27% to 28% of patients were considered to derive clinical benefit from toremifene. The dose range chosen for further study was 40 to 60 mg/d.
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PMID:Phase I and II studies of toremifene. 916 2

A 17-day-old Japanese boy was transferred to the hospital because of vomiting and impaired consciousness. His external genitalia was pigmented associated with small penis and penoscrotal hypospadias. He was diagnosed as suffering from adrenal deficiency according to severe electrolyte abnormality, moderate hypoglycemia, metabolic acidosis and extremely elevated 17-OHP and testosterone levels. He turned out to be a compound heterozygote of CYP21A2 mutations by genetic analysis. Through endocrinological evaluation, he seemed to have normal hypophyseal function, intact testosterone production and appropriate 5-alpha-reductase-2 activity. Partial androgen insensitivity could not be ruled out by slight decrease of SHBG in hCG loading test, although mutation was not detected on androgen receptor gene. This is a rare case of a male patient with 21-hydroxylase deficiency accompanied by hypospadias. As the cause of hypospadias in this case has yet to be elucidated, further investigation and careful follow-up are required.
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PMID:Hypospadias in a male patient with 21-hydroxylase deficiency. 1871 94