natgillin/translations-raw huggingface dataset:
In the osteoporosis treatment trials, FABLYN therapy resulted in consistent, statistically significant suppression of bone resorption and bone formation, as reflected by changes in serum and urine markers of bone turnover (e. g., C-telopeptide and markers of bone formation: osteocalcin, procollagen type 1 N-terminal propeptide, and bone-specific alkaline phosphatase).
C- telopeptida in označevalcev nastajanja kosti: osteokalcina, N- terminalnega propeptida prokolagena tipa 1 in za kost specifične alkalne fosfataze).
The suppression of bone turnover markers was evident by 3 months and persisted throughout the 36-month observation period in a sub-study of the PEARL study.
Supresija označevalcev premene kostnine je postala očitna po 3 mesecih in je v podštudiji študije PEARL trajala celotno 36- mesečno obdobje opazovanja.
9 5-year results from large, multinational fracture trial (PEARL)
5- letni rezultati velikega multinacionalnega preskušanja zlomov (PEARL)
The study population consisted of 8,556 postmenopausal women with osteoporosis as defined by low BMD (vertebral or hip BMD at least 2.5 standard deviations below the mean value for healthy young women).
Populacijo študije je sestavljalo 8. 556 žensk v postmenopavzi z osteoporozo, definirano z zmanjšano BMD (BMD hrbtenice ali kolka vsaj 2, 5 standardne deviacije pod povprečno vrednostjo pri zdravih mladih ženskah (T- vrednost)).
All women in the study received calcium (1,000 mg/ day) and Vitamin D (400-800 IU/ day).
Vse ženske v tej študiji so jemale kalcij (1. 000 mg/ dan) in vitamin D (400- 800 i. e. / dan).
Fracture incidence in postmenopausal women over 5 years
Pogostnost zlomov pri ženskah v postmenopavzi v obdobju 5 let
reduction (95% CI) vs. placebo New radiographic vertebral fractures
Relativno zmanjšanje tveganja (95% CI) v primerjavi s placebom
n=2,748
Novi rentgenski vretenčni zlomi Odstotni
n=2,744
n=2. 748
41%a
n=2. 744
Percentage of patients with new fracture New radiographic vertebral fracture in patients with ≥ 1
delež bolnic z novim zlomom Novi rentgenski vretenčni zlomi pri bolnicah z
(28%, 52%)
41% a (28%, 52%)
baseline fracture
izhodiščnim zlomom ≥ 1 Odstotni delež bolnic
Percentage of patients with new fracture New radiographic vertebral fracture in patients without any
z novim zlomom Novi rentgenski vretenčni zlomi pri bolnicah
8.7%
n=778 8, 7%
(21%, 57%)
42% b (21%, 57%)
prevalent fracture at baseline Percentage of patients with new fracture Non-vertebral fractures Percentage of patients with non-vertebral fracture
Odstotni delež bolnic z novim zlomom Nevretenčni zlomi Odstotni delež bolnic z
n=1,970 4.4% n=2,852 8.1%
4, 4% n=2. 852
n=1,970 7.4% n=2,852 10.4%
7, 4% n=2. 852
41%c (23%, 55%) 24%d (9%, 36%)
41% c (23%, 55%)
All clinical fractures
nevretenčnim zlomom Vsi klinični zlomi Odstotni delež bolnic s
n=2,852 n=2,852
10, 4% n=2. 852
25%e
24% d (9%, 36%)
Percentage of patients with clinical fracture Abbreviations: n= number of patients; CI = Confidence Intervals a
kliničnim zlomom
(12%, 36%)
25% e (12%, 36%)
p < 0.0001; b p = 0.0004; c p = 0.0002; d p = 0.0020; e p = 0.0004
Okrajšave: n= število bolnic; CI = intervali zaupanja ap < 0, 0001; bp = 0, 0004; cp = 0, 0002; dp = 0, 0020; e p = 0, 0004
-Radiographic vertebral fractures
- Rentgensko ugotovljeni vretenčni zlomi
FABLYN significantly decreased the incidence of new radiographic vertebral fractures (excluding worsening of previous fractures) from 9.3% for placebo to 5.6% for FABLYN (relative risk reduction = 41%, p < 0.0001).
Zdravilo FABLYN je signifikantno zmanjšalo pogostnost novih rentgensko ugotovljenih vretenčnih zlomov (poslabšanje že od prej obstoječih zlomov tu ni vključeno) z 9, 3% pri placebu na 5, 6% pri zdravilu FABLYN (relativno zmanjšanje tveganja = 41%, p < 0, 0001).
In women with a prevalent vertebral fracture at baseline, FABLYN significantly reduced the incidence of new vertebral radiographic fractures from 14.2% for placebo to 8.7% for FABLYN (relative risk reduction = 42%, p = 0.0004).
10 Pri ženskah s prevladujočim vretenčnim zlomom v izhodišču je zdravilo FABLYN signifikantno zmanjšalo pogostnost novih rentgenskih vretenčnih zlomov s 14, 2% pri placebu na 8, 7% pri zdravilu FABLYN (relativno zmanjšanje tveganja = 42%, p = 0, 0004).
In women without any prevalent vertebral fractures at baseline, the incidence of new radiographic vertebral fractures was significantly reduced from 7.4% for placebo to 4.4% for FABLYN (relative risk reduction = 41%, p = 0.0002).
Pri ženskah brez prevladujočih vretenčnih zlomov v izhodišču se je pomembno zmanjšala pogostnost novih rentgenskih vretenčnih zlomov s 7, 4% pri placebu na 4, 4% pri zdravilu FABLYN (relativno zmanjšanje tveganja = 41%, p = 0, 0002).
Significantly fewer women experienced multiple radiographic vertebral fractures in the FABLYN treatment group versus the placebo group throughout 5 years of dosing (p < 0.0001).
V skupini, zdravljeni z zdravilom FABLYN, je dobilo v 5 letih zdravljenja po več rentgenskih vretenčnih zlomov signifikantno manj žensk kot v skupini s placebom (p < 0, 0001).
Significantly fewer women treated with FABLYN experienced moderate or severe vertebral fractures (as determined by the Genant scale) compared to women treated with placebo (5.2% placebo-treated women versus 3.3% FABLYN-treated women; p = 0.0006).
Zmerni ali težki vretenčni zlomi (klasificirane po Genantovi lestvici) je dobilo signifikantno manj žensk od tistih, ki so jemale placebo (5, 2% žensk s placebom in 3, 3% žensk, zdravljenih z zdravilom FABLYN; p = 0, 0006).
10 -Non-vertebral fractures
- Nevretenčni zlomi
FABLYN significantly decreased the incidence of non-vertebral fractures from 10.4% for placebo to 8.1% for FABLYN (relative risk reduction = 24%, p = 0.0020).
Zdravilo FABLYN je signifikantno zmanjšalo pogostnost nevretenčnih zlomov z 10, 4% pri placebu na 8, 1% pri zdravilu FABLYN (relativno zmanjšanje tveganja = 24%, p = 0, 0020).
The reduction in the incidence of non-vertebral fractures was also observed in postmenopausal women with severe osteoporosis (defined as a baseline lumbar spine BMD T-score ≤ -2.5 + prevalent fracture or BMD T-score ≤ -3) (p = 0.0183).
Zmanjšanje pogostnosti nevretenčnih zlomov so opazili tudi pri ženskah v postmenopavzi s hudo osteoporozo (opredeljeno kot T- vrednost BMD ledvene hrbtenice na začetku študije ≤ - 2, 5 + prevladujoč zlom ali T- vrednost ≤ - 3) (p = 0, 0183).
-All clinical fractures
- Vsi klinični zlomi
FABLYN significantly decreased the incidence of all clinical fractures from 12.1% for placebo to 9.3% for FABLYN (relative risk reduction = 25%, p = 0.0004).
Zdravilo FABLYN je signifikantno zmanjšalo pogostnost vseh kliničnih zlomov z 12, 1% pri placebu na 9, 3% pri zdravilu FABLYN (relativno zmanjšanje tveganja = 25%, p = 0, 0004).
In a 3-year substudy of the PEARL study (n=760), FABLYN significantly increased BMD (compared to placebo) at lumbar spine (3.3%), total hip (3.0%), femoral neck (3.3%), greater trochanter (3.6%), intertrochanteric area (2.6%), Ward’ s triangle (5.9%) and forearm (1.8%) at 3 years.
V 3- letni podštudiji študije PEARL (n=760) je zdravilo FABLYN po 3 letih signifikantno zvečalo BMD (v primerjavi s placebom) v ledveni hrbtenici (3, 3%), celotnem kolku (3, 0%), stegneničnem vratu (3, 3%), velikem trohantru (3, 6%), intertrohanternem predelu (2, 6%), Wardovem trikotniku (5, 9%) in podlaktu (1, 8%).
FABLYN also significantly increased whole body bone mineral content (BMC), compared to placebo, at 3 years.
Zdravilo FABLYN je v primerjavi s placebom po 3 letih tudi signifikantno zvečalo vsebnost kostnih mineralov v vsem telesu (BMC- Bone Mineral Content).
An analysis was conducted of the subjects who were referred to their physician for consideration of treatment with an alternative osteoporosis medicinal product if one of the following was observed: a) ≥ 7% BMD loss at LS or ≥ 10% BMD loss at femoral neck at Month 12; b) ≥ 11% BMD loss at lumbar spine (LS) or ≥ 14% BMD loss at femoral neck at Month 24; c) ≥ 2 on-study radiographic vertebral fractures by Month 24.
Opravili so analizo oseb, ki so jih napotili k njihovemu zdravniku za oceno možnosti zdravljenja s kakšnim drugim zdravilom za osteoporozo, če so opazili kaj od naslednjega: a) ≥7% izgubo BMD v ledveni hrbtenici (LS) ali ≥10% izgubo BMD v stegneničnem vratu v 12. mesecu; b) ≥11% izgubo BMD v LS ali ≥14% izgubo BMD v stegneničnem vratu v 24. mesecu; c) ≥2 rentgenskemu vretenčnemu zlomu, nastalim med študijo do 24. meseca.
These referrals were significantly less frequent in the FABLYN group (0.9%) than in the placebo group (3.3%).
Te napotitve so bile signifikantno redkejše v skupini z zdravilom FABLYN (0, 9%) kot v skupini s placebom (3, 3%).
The study population consisted of 497 women with osteoporosis as defined by low vertebral BMD (T-score ≤ 2.5).
Populacijo študije je sestavljalo 497 žensk z osteoporozo, definirano z majhno BMD vretenc (T- vrednost ≤ 2, 5).
All women in the study received calcium (600-1200 mg/ day) and Vitamin D (400-800 IU/ day).
Vse ženske v tej študiji so jemale kalcij (600- 1. 200 mg/ dan) in vitamin D (400- 800 i. e. / dan).
In this study, FABLYN significantly increased spine and hip (total hip and all subcomponents of the hip) BMD by 2 to 4%.
V tej študiji je zdravilo FABLYN signifikantno zvečalo BMD hrbtenice in kolka (kolka kot celote in vseh sestavnih delov kolka) za 2 do 4%.
Bone histomorphometry
11 Histomorfometrija kosti
11 Lasofoxifene may be associated with benign endometrial effects: endometrial cystic change viewed on ultrasound and histological benign cystic atrophy (a variant of atrophic endometrium), contributing to approximately 1.5 mm increase in mean endometrial thickness.
Lasofoksifen je lahko pri nekaterih osebah povezan z benignimi učinki na endometrij: cistično spremembo endometrija, vidno z ultrazvokom, in histološko benigno cistično atrofijo (varianta atrofičnega endometrija), ki prispeva k približno 1, 5- milimetrskem povečanju povprečne debeline endometrija.
In clinical practice, these benign findings do not warrant further evaluation in women with no vaginal bleeding, in accordance with guidelines for postmenopausal women (see section 4.4).
V klinični praksi ti benigni izvidi, v skladu s smernicami za ženske v postmenopavzi, ne upravičujejo nadaljnjih diagnostičnih postopkov pri ženskah, ki nimajo krvavitev iz nožnice (glejte poglavje 4. 4).
Placebo-treated women had a 1.9% incidence in cystic change over 3 years, whereas the FABLYN-treated women had a 20.4% incidence.
Pogostnost cističnih sprememb v obdobju 3 let, je bila pri ženskah, ki so jemale placebo, 1, 9- odstotna, pri ženskah zdravljenih z zdravilom FABLYN pa 20, 4- odstotna.
Placebo-treated women had a 0.7 mm mean decrease from baseline in endometrial thickness over 3 years, whereas the FABLYN-treated women had a 1.4 mm mean increase.
Pri ženskah, ki so prejemale placebo, se je v obdobju 3 let debelina endometrija zmanjšala povprečno za 0, 7 mm od izhodiščne debeline, pri ženskah, zdravljenih z zdravilom FABLYN, pa se je za povprečno 1, 4 mm zvečala.
In all women with a uterus at baseline, histologically benign endometrial polyps were reported in 34 of 2,302 (1.5%) FABLYN-treated women versus 18 of 2,309 (0.8%) placebo-treated women.
Od vseh žensk, ki so na začetku študije imele maternico, so o histološko benignih endometrijskih polipih poročali pri 34 od 2. 302 (1. 5%) žensk, zdravljenih z zdravilom FABLYN, v primerjavi z 18 od 2. 309 (0, 8%) žensk, ki so jemale placebo.
In a subset of the study population designed to look at endometrial histology (1,080 patients) with a TVU at 3 years, histologically benign endometrial polyps were reported in 20 of 366 (5.5%) FABLYN-treated women and 12 of 360 (3.3%) placebo-treated women.
V podskupini študijske populacije, kjer so proučevali endometrijsko histologijo (1. 080 bolnic) s TVU po 3 letih, so poročali o histološko benignih endometrijskih polipih pri 20 od 366 (5, 5%) žensk, zdravljenih z zdravilom FABLYN, in 12 od 360 (3, 3%) žensk, ki so jemale placebo.
The overall incidence of vaginal bleeding was low (≤ 2.6% in all treatment groups).
Skupna pogostnost vaginalnih krvavitev je bila majhna (≤ 2, 6% v vseh zdravljenih skupinah).
Vaginal bleeding was reported in 74 (2.6%) FABLYN-treated women versus 37 (1.3%) placebo-treated women.
O krvavitvah iz nožnice so poročali pri 74 (2, 6%) ženskah, zdravljenih z zdravilom FABLYN, in pri 37 (1, 3%) ženskah, ki so jemale placebo.
The number of subjects discontinuing treatment as a result of vaginal bleeding was low [FABLYN:
Število oseb v preiskavi, ki so prekinile zdravljenje zaradi vaginalnih krvavitev, je bilo majhno [zdravilo FABLYN:
The number of hysterectomies in the FABLYN-treated group (27/ 2,302 patients, 1.2%) and the placebo-treated group (24/ 2,309 patients, 1.0%) were similar.
Število histerektomij v skupini, zdravljeni z zdravilom FABLYN (27/ 2. 302 bolnic, 1, 2%), in v skupini, ki je jemala placebo (24/ 2. 309 bolnic, 1, 0%), je bilo podobno.
To assess the effect of FABLYN on diagnostic uterine procedures (i. e., hysteroscopy, saline infused sonohysterogram, endometrial biopsy, polypectomy or dilation and curettage), an analysis was conducted on women without planned TVU surveillance (4,055 patients).
Da bi ocenili vpliv zdravila FABLYN na postopke maternične diagnostike (npr. histerektomija, sonohisterogram z vbrizganjem fiziološke raztopine, endometrijska biopsija, polipektomija ali dilatacija in kiretaža), so analizirali ženske brez načrtovanega nadzora s TVU (4. 055 bolnic).
More FABLYN-treated patients (7.0%) had a diagnostic procedure compared to placebo-treated patients (2.7%).
Tak diagnostičen postopek je imelo več bolnic, zdravljenih z zdravilom FABLYN (7, 0%), kot bolnic, ki so jemale placebo (2, 7%).
Diagnostic uterine procedures were performed in a greater number of FABLYN-treated patients as a result of vaginal bleeding (as mandated by the protocol) and asymptomatic endometrial findings (e. g., suspected uterine polyps, endometrial thickness).
Razlog, da so postopek maternične diagnostike opravili pri večjem številu bolnic zdravljenih z zdravilom FABLYN kot pa je narekoval protokol, so bile vaginalne krvavitve (kot je narekoval protokol) in asimptomatske endometrijske ugotovitve (npr. sum na maternične polipe, zadebelitev endometrija).
Effects on breast:
12 Učinki na dojke:
Over the 5 years of the PEARL study (involving 8,556 patients), FABLYN treatment compared to placebo reduced the risk of invasive breast cancer by 85% (placebo:
V 5 letih študije PEARL (ki je zajelo 8. 556 bolnic) je zdravljenje z zdravilom FABLYN v primerjavi s placebom zmanjšalo tveganje invazivnega raka dojke za 85% (placebo:
3 (0.1%); HR 0.15 (CI 0.04, 0.50)), the risk of all breast cancer by 79% (placebo:
3 (0, 1%); HR 0, 15 (CI 0, 04, 0, 50)), tveganje raka dojke ne glede na vrsto raka za 79% (placebo:
5 (0.2%); HR 0.21 (CI 0.08, 0.55)), the risk of estrogen receptor (ER) positive invasive breast cancer by 83% (placebo:
5 (0, 2%); HR 0, 21 (CI 0, 08, 0, 55)), tveganje invazivnega raka dojke, pozitivnega na estrogenske receptorje (ER), za 83% (placebo:
3 (0.1%); HR 0.17 (CI 0.05, 0.57)) and the risk of estrogen receptor (ER) positive breast cancer by 81% (placebo:
3 (0, 1%); HR 0, 17 (CI 0, 05, 0, 57)) in tveganje invazivnega raka dojke, pozitivnega na ER, za 81% (placebo:
4 (0.1%); HR 0.19 (CI 0.07, 0.56)).
4 (0, 1%); HR 0, 19 (CI 0, 07, 0, 56)).
12 Effects on lipid metabolism and cardiovascular risk:
Učinki na presnovo lipidov in kardiovaskularno tveganje:
The effect of FABLYN on the lipid profile was evaluated in a 3-year substudy of the PEARL study; the substudy enrolled 1,014 postmenopausal women.
Vpliv zdravila FABLYN na profil lipidov so ovrednotili v 3- letni podštudiji študije PEARL; podštudija je zajela 1. 014 žensk v postmenopavzi.
Relative to placebo, FABLYN significantly decreased total cholesterol, LDL cholesterol, LDL-associated apolipoprotein B-100, and high sensitivity C-reactive protein (median changes -10.4%, -15.8%, -11.8%, -12.5%, respectively); no significant changes versus placebo were seen for HDL cholesterol or VLDL cholesterol.
V primerjavi s placebom je zdravilo FABLYN signifikantno zižalo celotni holesterol, LDL holesterol, z LDL povezani apolipoprotein B- 100 in C- reaktivni protein z veliko občutljivostjo (mediane spremembe - 10, 4%, - 15, 8%, - 11, 8% oziroma - 12, 5%); pri HDL holesterolu in VLDL holesterolu signifikantnih sprememb v primerjavi s placebom niso našli.
Statistically significant increases were seen for apolipoprotein A-1, which is associated with HDL cholesterol, and serum triglycerides (median changes vs. placebo 6.1% and 4.9%, respectively).
Statistično signifikantno zvišanje so ugotovili pri apolipoproteinu A- 1, ki je povezan s HDL holesterolom, in serumskih trigliceridih (mediane spremembe glede na placebo 6, 1% oziroma 4, 9%).
At 5 years in the overall study population (N=8,556), the incidence of major coronary events, including coronary death, non-fatal myocardial infarction, new ischemic heart disease, hospitalization for unstable angina, and revascularisation procedures, was significantly lower.
Po 5 letih je bila v celotni populaciji študije (N=8. 556) pogostnost pomembnih koronarnih dogodkov, vključno s koronarno smrtjo, miokardnim infarktom, ki se ni končal z bolničino smrtjo, novo ishemično boleznijo srca, hospitalizacijo zaradi nestabilne angine in postopki revaskularizacije, signifikantno manjše.
There were 0.51 events/ 100 patient-years for FABLYN-treated patients compared to 0.75 events/ 100 patient-years in placebo-treated patients (HR 0.68; 95% CI 0.50, 0.93, p= 0.016).
Pri bolnicah, zdravljenih z zdravilom FABLYN, je bilo 0, 51 dogodka/ 100 bolnikov- let, pri bolnicah, ki so dobivale placebo, pa 0, 75 dogodka/ 100 bolnikov- let (HR 0, 68; 95% CI 0, 50, 0, 93, p= 0, 016).
There were 0.48 events/ 100 patient years in the placebo group and 0.36 events/ 100 patient years among FABLYN-treated patients (HR = 0.75; 95% CI 0.51, 1.10, p = 0.140).
V skupini s placebom je bilo 0, 48 dogodka/ 100 bolnikov- let in 0, 36 dogodka/ 100 bolnikov- let med bolnicami, zdravljenimi z zdravilom FABLYN (HR = 0, 75; 95% CI 0, 51, 1, 10 p = 0, 140).
Effects on vulvar and vaginal atrophy (VVA):
Učinki na atrofijo vulve in vagine (VVA- vulvar and vaginal atrophy):
The efficacy of FABLYN in the treatment of VVA was investigated in two 12-week Phase 3 studies in postmenopausal women with moderate or severe signs and symptoms of VVA, regardless of osteoporosis status (involving 889 patients).
Učinkovitost zdravila FABLYN za zdravljenje VVA so raziskali v dveh 12- tedenskih študijah faze 3 pri ženskah v postmenopavzi z zmernimi ali težkimi znaki in simptomi VVA, ne glede na status osteoporoze (zajeli sta 889 bolnic).
In both studies, it decreased the severity of the subject’ s most bothersome baseline VVA symptom, decreased vaginal pH, decreased the percentage of vaginal parabasal cells from the maturation index (MI) and increased the percentage of vaginal superficial cells from the MI.
V obeh študijah je zdravilo FABLYN zmanjšalo stopnjo izraženosti najbolj motečega simptoma VVA bolnice ob začetku študije, znižanega nožničnega pH, zmanjšalo odstotni delež vaginalnih parabazalnih celic iz indeksa dozorevanja (MI- maturation index) in zvečalo odstotni delež vaginalnih površinskih celic iz MI.
Pharmacokinetic data from over 2,000 postmenopausal women including patients in selected osteoporosis clinical trials contributed to a population pharmacokinetic analysis.
K populacijski farmakokinetični analizi so prispevali farmakokinetični podatki, pridobljeni pri okrog 2. 000 ženskah v postmenopavzi, vključno z bolnicami v izbranih kliničnih preskušanjih osteoporoze.
Absorption:
13 Absorpcija:
The apparent volume of distribution (V/ F) of lasofoxifene in postmenopausal women is approximately 1,350 l.
Navidezni volumen porazdelitve (V/ F) lasofoksifena pri ženskah v postmenopavzi je približno 1. 350 l.
Lasofoxifene is highly bound to proteins in human plasma (> 99%).
Lasofoksifen se v velikem deležu veže na beljakovine v človeški plazmi (> 99%).
Lasofoxifene binds to both albumin and α 1-acid glycoprotein; however, it does not affect the binding of either warfarin or propranolol.
Lasofoksifen se veže tako na albumin kot na α1- kisli glikoprotein; vendar pa ne vpliva na vezavo niti varfarina niti propranolola.
13 Metabolism:
Presnova:
The binding affinities of the major circulating metabolites of lasofoxifene were at least 31-fold and 18-fold less than those of lasofoxifene for the estrogen receptor alpha and the estrogen receptor beta, respectively, indicating that these metabolites are unlikely to contribute to the pharmacologic activity of lasofoxifene.
Vezavna afiniteta poglavitnih presnovkov lasofoksifena v krvi za estrogenski receptor alfa in estrogenski receptor beta je bila vsaj 31- krat oziroma 18- krat manjši od vezavne afinitete lasofoksifena, kar kaže, da ni verjetno, da bi ta presnovka prispevala k farmakološki aktivnosti lasofoksifena.
Oxidation, by multiple cytochrome P450s including CYPs 2D6 and 3A4/ 5, and conjugation of lasofoxifene are the two primary mechanisms of elimination of lasofoxifene from the systemic circulation.
Oksidacija z več citokromi P450, med drugim CYPs 2D6 in 3A4/ 5, in konjugacija lasofoksifena sta dva primarna mehanizma odstranjevanja lasofoksifena iz sistemskega krvnega obtoka.
The apparent oral clearance (CL/ F) of lasofoxifene in postmenopausal women is approximately 6.6 l/ hr.
Navidezni peroralni očistek (CL/ F) lasofoksifena pri ženskah v postmenopavzi je približno 6, 6 l/ h.
Following oral administration of 14C-labeled lasofoxifene in solution to humans, approximately 72% of the radioactive dose was recovered by day 24 (approximately 66% in feces and 6% in urine).
Po peroralnem dajanju lasofoksifena v raztopini, označenega s 14C so v naslednjih 24 dneh prestregli približno 72% radioaktivnega odmerka (približno 66% v blatu in 6% v urinu).
Linearity/ non-linearity:
Linearnost/ nelinearnost:
At steady state, the half-life of lasofoxifene in postmenopausal women is approximately 6 days, resulting in small fluctuations in concentrations over the 24-hour dosing interval.
V stanju dinamičnega ravnovesja znaša razpolovni čas lasofoksifena pri ženskah v postmenopavzi približno 6 dni, kar pri 24- urnem presledku med odmerki povzroča majhna nihanja koncentracij.
Elderly:
14 Starejše bolnice:
This analysis included 2,049 postmenopausal women consisting of 85.5% Caucasian, 8.6% Hispanic, 3.4% Asian, and 1.9% African American.
V to analizo je bilo vključenih 2. 049 žensk v postmenopavzi, in sicer 85, 5% belk, 8, 6% Latinoameričank, 3, 4% Azijk in 1, 9% Afroameričank.
14 Gender:
Spol:
Lasofoxifene was studied, as a single 0.25 mg dose, in healthy subjects and subjects with mild or moderate hepatic impairment.
Lasofoksifen so v obliki enkratnega 0, 25 miligramskega odmerka proučevali pri zdravih osebah in osebah z blagimi ali zmernimi okvarami jeter.
Plasma lasofoxifene exposure was approximately the same in healthy subjects as in subjects with mild hepatic impairment (Child-Pugh Class A) and was modestly increased (38%) in subjects with moderate hepatic impairment (Child-Pugh Class B) compared to healthy subjects.
Izpostavljenost lasofoksifenu v plazmi je bila pri zdravih osebah približno enaka kot pri osebah z blago okvaro jeter (razred A po Child- Pughovi lestvici), pri osebah z zmerno okvaro jeter (razred B po Child- Pughovi lestvici) pa je bila v primerjavi z zdravimi osebami zmerno zvečana (38%).
Subjects with severe hepatic impairment have not been studied (see section 4.4).
Oseb s težko okvaro jeter niso proučevali (glejte poglavje 4. 4).
Since less than 2% of lasofoxifene is recovered in urine as unchanged active substance, a study in subjects with renal insufficiency was not conducted.
Ker se v urinu pojavi manj kot 2% lasofoksifena v obliki nespremenjene zdravilne učinkovine, pri osebah z insuficienco ledvic niso opravili nobene študije.