P296 Efficacy and tolerability of the 7-day transdermal estradiol patch S21102 in the treatment of postmenopausal symptoms

P294

P295

A 25% DIFFERENCE IN E2 CONCENTRATIONS CONTAINED IN A MATRIX-TYPE PATCH, DOES NOT AFFECT THE DAILY E2 RELEASE

PHARMACOKINETICS OBTAINED WITH

I RocheP, YDonauolob,J Collette’,R Jochemsen”,JY Reginstef, Y Tsouderoti aIRIS,6 placedesPleiades,92415Courbevoie,France.bOptimed,2 av de Vignate, 38610-Gieres,France, “Chu Liege, B-4000 SartTilman,Belgium

OF ESTRADIOL BLOOD CONTENT S21102, A NEW 7-DAY PATCH

0 Lhote, ZRocher,R Jochemsen,Y Tsouderos IRIS, 6 placedesPltiades,92415Courbevoie,France

A pharmacokineticstudy was conductedin 24 post-menopausal womento comparethe one-weektime-profilesof E2 following a 7day applicationof S21102to two applicationson days1 and 5 of a marketedreservoirpatch (ESTRADERM TTS@SO).S21102is a S21102is a newonce-a-week matrix-type patchcontainingE2 anda newmatrix-typetransdermal patchcontaining17Bestradiol(E2) and penetrationenhancer.To assess the daily influenceof the matrix E2 a penetrationenhancer.The two patchesare designedto deliver 50 concentrationon the plasmaestradiollevel, two prototypeswith the pg E2 a day. The study was set-upwith a two-way randomised samematrix, samearea,containingeither2% or 2.5% of E2, have cross-overdesign.E2 wasassayedin blood plasma,taken every 12 beencomparedtogetherand with a marketedreservoirpatch. The hours,by a specificRIA. The limit of quantificationwas5 pg.ml’. study was set-upwith a randomisedcross-overdesign. E2 was The concentration-timeprofiles exhibited less peak-to-through assayedin blood plasmaevery 12 hoursfor a week by a specific fluctuationswith S21102than with TTS 50. Slight fluctuationsof RIA. The limit of quantificationwas5 pg.ml-‘. E2 concentrationswere observedwith S21102,namely everyday The E2 concentration-timeprofiles showedno differencebetween evening concentrationswere higher than morning ones. Such the two matrix patches. In each case,a sustained“plateau” was differencescould not be due to endogenousE2 secretion.More observedover the weekof application.With the reservoirpatch,the likely, they are attributable to circadian changeseither in the E2 plasmaprofile was clearly different with peaks and nadir. release/absorption rate,and/orE2 clearance. However,no significantdifferencein AU(& wasseen,suggesting No significant difference was seen in AU& suggesting bioequivalencewith regardto the total amountof E2 releasedover a bioequivalencebetweenS21102and TTS 50 with regard to the week,both betweenthe two S21102prototypesandbetweeneachof amountabsorbed over a week,but not with regardto the daily rateof themandthe reservoirpatch. absorption. Each of the S21102prototypes,containingeither 2% or 2.5% of S21102 is, therefore, a good candidatefor E2 replacementby estradiol, is a good candidatefor E2 replacementtherapy by transdermal route,with once-a-week application. transdermal route.

P297

P296

25MG OESTRADIOL IMPLANTS AND 1MG NORETHISTERONE AS CONTINUOUS COMBINED HRT IN THE OVER 60’s.

EFFICACY AND TOLERABILITY OF THE 7-day TRANSDERMAL ESTRADIOL PATCH S21102 IN THE TREATMENT OF POSTMENOPAUSAL SYMPTOMS.

C PelissieP,A Mallef, M Agog&, M Renaud”,MH BreiC’,A Gritnard”, I Roche), Y Tsouderosb. *A.M.G.O.P., 72 rue d’Auteui1,75016Paris,France.b IRIS, 6 place desP1Ciades, 92415Courbevoie,France. A once-a-weektransdermalestradiol patch (S21102) has been developedfor HRT. This patchcontainsan absorptionenhancerand delivers5Ougof E2 every 24 hours. The initial evaluationof the patch focused on efficacy, adhesivenessand local tolerance. Seventy-four postmenopausal women were enrolled in an open multicentric study. All womenhad previously beentreatedfor at least3 monthswith a reservoirtransdermal patchof E2 andreceived two (sequential)cycles of treatment (4 patches/cycle). Results: Efficacy wasjudged as good (92%), average(7%) or insufficient (1%) by the investigatorsbasedon the climactericsymptomsand clinical signs of hormonal impregnation. Local tolerancewas reportedto be good (77%) acceptable(20%) or bad (3%) by the patients. Adhesivenesswas assessed for eachpatch during the 2 cyclesand for 55% of the patientswasidenticalor betterthan the adhesiveness of the reservoirpatch previously used. Differences could be recognisedbetweenhorizontal and vertical applications. The once-a-weekpatch was judged to be more esthetically acceptableby 49% of the patients. In addition,66% of themfound that the once-a-weekpatch left lessglue tracesascomparedto the othermodels. In conclusion,the once-a-weektransdermalE2 patch S21102is effective in the treatment of climacteric symptomsand is well tolerated. 208

N.Panav,J. W.W.Studd,R. Sands,D. Zamblera. Departmentof Obstetrics& Gynaecology,ChelseaandWestminster Hospital,FulhamRoad,LondonSW109NH, U.K. We aimedto demonstrate that in womenover 60 yearsof age,low dosecontinuouscombinedHRT benefitsthe skeletalsystemwhilst minimising problemssuch as withdrawal bleeds, endometrial hyperplasiaand progestogenicside effects. 19 postmenopausal womenwererecruitedand seenat 6 monthly intervalsfor 1 year, receiving 25mg oestradiol implants at each visit and lmg norethisterone daily. Patientswereissuedwith daily menstrualand symptomdiariesandthe investigationscarriedout were; FSH & E2 levels- transvaginalultrasoundscansfor endometrialthickness; DEXA bone densitometryand pipelle samplingof endometrium. The meanageof recruitmentwas62 years. The meanbody mass index(BMI) waswithin the normalrangeat 26.5. 3 womenwithdrew early, 2 due to breakthroughbleedingand 1 due to progestogen intolerance. Median oestradiollevels rose from 77pmol/l pretreatmentto 275pmol/lat 1 year. TheFSH levelsdroppedfrom 73.6 to 3.65(iu/l) during that time. Median endometrialthickness,by transvaginalultrasoundscan,remainedunchangedat 4mm,pre and 1 year posttreatment. Endometrialbiopsiesat I year or at drop-out confirmedsuppression in all but 1 patientwho had a proliferative endometrium. Continued