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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of (deaminohydroxy)toremifene in humans: a new, selective estrogen-receptor modulator (2000)
    Springer
    European journal of clinical pharmacology 56 (2000), S. 469-475 
    Details
    ISSN: 1432-1041
    Keywords: Key words (Deaminohydroxy)toremifene ; Pharmacokinetics ; Triphenylethylene ; FC-1271a ; SERM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Purpose: New selective estrogen-receptor modulators for the treatment and prevention of osteoporosis, cardiovascular disease and breast cancer are currently the focus of intense research. (Deaminohydroxy)toremifene (Z-2-[4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy]ethanol; FC-1271a) has been shown to prevent bone resorption in rats while having no or weak estrogen-like effects on the uterus, which makes it a good candidate drug for osteoporosis prevention. Our purpose here was to examine the pharmacokinetics of (deaminohydroxy)toremifene in humans included in two phase-I studies. Methods: The first was a single-dose, dose-escalation study with 28 healthy male volunteers. Doses ranged from 10 mg to 800 mg. The second study was conducted during a 12-week period with 40 healthy, post-menopausal women, who received repeated oral doses of 25–200 mg. Standard pharmacokinetic parameters were assessed. Results: In the single-dose study, time to reach peak concentration (tmax) ranged from 1.3 h to 4.0 h; peak concentration (Cmax) ranged from 15 ng/ml to 445 ng/ml; and the estimated terminal elimination half-life (mean ± SD; t1/2) was 24.8 ± 7.0 h. In the repeated-dose study, tmax ranged from 1.9 h to 2.6 h at 6 weeks and from 2.5 h to 2.9 h at 12 weeks. Cmax ranged from 295 ng/ml to 1043 ng/ml at 6 weeks and from 25 ng/ml to 1211 ng/ml at 12 weeks. The average t1/2 at all dose levels was 29.7 ± 1.5 h (overall mean ± SD). Strong linear correlations between the dose and Cmax and between the dose and the area under the curve were observed in both studies. Conclusion: Our results indicate that (deaminohydroxy)toremifene has pharmacokinetics suitable for single daily dosing. The prophylactic use of this agent in women susceptible to development of osteoporosis, cardiovascular disease and breast cancer could, therefore, be tested using a once-daily dosing schedule similar to those of other hormone-replacement therapy regimens.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280000176
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  • 2
    Electronic Resource
    Electronic Resource
    Infant mortality in a region of Finland, 1968–1982 (1986)
    Springer
    European journal of pediatrics 145 (1986), S. 467-470 
    Details
    ISSN: 1432-1076
    Keywords: Infant mortality ; Neonatal mortality ; Postneonatal mortality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Infant mortality in a region of Finland with about 450000 people and 5400 annual births was examined during a 15-year period, 1968–1982. Total infant mortality declined from 15.8 per 1000 live births in 1968 to 5.0 in 1982. The lowering of neonatal mortality accounted for the decline, as postneonatal mortality remained at the same level throughout the study period. Despite a decrease of nearly 80%, perinatal disorders remained the leading category of primary causes of death. Mortality from congenital malformations decreased by 50%, mortality from sudden infant death syndrome increased from 0.2 to 0.9 per 1000 live births while mortality from accidents, infectious diseases and other diseases remained minor causes of death with no change in frequency. In the low birth weight category, postponement of deaths from early to late neonatal and postneonatal periods occurred, but total infant mortality in the low birth weight category declined by about 60%. During the last two 3-year periods, decrease in birth weight-specific infant mortality was found in the 500–999 g and 〉2500 g categories. The reasonably high standard of living, good educational level of mothers, well organized primary maternal and child health services and the rapid advances in obstetric and neonatal care equally available and regionalized, have contributed to the favourable progress in infant mortality in Finland.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02429044
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    Paper (German National Licenses)
    Fulltext
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