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F151 Pharmacokinetics of a new estradiol matrix patch in healthy postmenopausal volunteers and symptomatic women
B150 (cant)
F150 CLiNICAL
GROUPING
OF HORMONE THERAPY
REPLACEMENT
J Hutton, S h’lerchko, L Toop, D Moore, L Scatdon and W Bennett, Pharmaceutical Management Agency, P 0 Box 10-254, Wellington, New Zealand.
5.High
In New Zealand (NZ), some hormone replacement therapies (HRTs) have received higher subsidies than others despite similar therapeutic effects. The aim of this study was to determine if the HRTs available in NZ could be grouped to allow more rational dete~ination of subsidies. The literature was researched, and clinicians and drug companies consulted. The resultant analysis showed there is no difference between the therapeutic outcomes of oral HRT and tr~sde~al HRT. Despite considerable individual variability, the therapeutic outcome of HRTs allowed their division into five, rather than three, groups according to the oestrogen dose: Group Oestrogen Type ~oselstrength l.Low Conjugated equine 0.3mg Transdermal oestradiol 25mcg 2.Medium”low Oestradiol valerate Img 17B-oestradiol lmg Conjugated equine 0.625mg 3.Medium Transde~al oestradiol 50mcg 3.9mg Transdermal oestradiol Oestradioi implant 50mg Oestradiol valerate 4.Medium-high 2mg 17B-oestradiol 2nv.s
Conjugated equine Transdermal oestradiol Tr~sde~~ oestradiol Oestradiol implant
1.25mg 100mcg 7.8mg 1OOmg
This grouping should aliow a more rational determination of the public subsidies for HRTs.
Continued
F151
F152
PHARMACOKINETICS OF A NEW ESTRADIOL MATRIX PATCH IN HEALTHY POSTMENOPAUSAL VOLU~EE~S AND SYMPTOMATIC WOMEN
TOLERABILITY AND ADHESION CHARACTERISTICS A NEW MATRIX PATCH (Estr~derm MX 50)
P boiled L Botta’, G Lej%r(;‘t F Ezzd* Ciba-Geigy Basle’, Switzerland and Rueji-Malmaison’, France. The pharmacokinetics (PK) of a new transdermal estradiol (E2) matrix patch, Estrade~ MX, were investigated in healthy postmenopausal volunteers and symptomatic women. E2 was measured in plasma by highly specific RIA. E2 concentrations were corrected for endogenous baseline by subtraction. Bioavailability of E2 from the matrix patch delivering 5Oug E2/day (MX50) was compared to the conventional membrane system, Estraderm TTS 50 (ITSSO), in 34 volunteers at steady state (ss} during a 96 h application (Study A). Mean E2 AUC, (O-96h) [h.pg/mL] was 3678 for MXSO and 3361 for TTSSO, with a 95% CI for the AUC ratio of (0.91, 1.16) . Average plasma levels C,,[pgimL] were 36.9 and 3 I. 1, and mean fluctuation indices (C,,C,“/C,,) were 1.03 and 2.16, respectively. Additional PK data after 12 weeks treatment of symptomatic women were obtained from two clinical trials, one with MXSO (n=49, Study B) and one with MXSO (n=53) and MXIOO (n=47, Study C). Mean E2 levels ]pg/mL] in symptomatic women affer 12 weeks treatment were 36.2 with MXSO (Study B), and 47.9 with MXSO and 103.1 with MXIOQ (Study C). MX50 is bioequivalent to ‘ITS50 for extent of E2 absorption (AUC). Due to differences in patch design and composition (matrix technolo~, lack of ethanok), MX produces less ~uctuating E2 levels and no distinct peak (C,,) . Average E2 concentrations are similar in healthy sub.jects and s~ptomatic women, and E2 levels double from MX50 to MX 100 in a clinical setting. 90
OF
G Della GOD&, RS Berge8, JA Ct&5~‘, CO Dillar$, ‘Ciba-Geigy Corp. NJ; ‘U~NJ, RW Medical School, New Brunswick, NJ; 3Hilltop Research Inc. NJ; Hilltop Research Inc. FL; 4Hilltop Pharmatest Inc.OH, USA. This open label (obse~er-Baird), r~domised, multicen~e study compared skin tolerability and adhesion characteristics of Estraderm TTS 50 (TTS) with a new matrix patch system (Estraderm MX 50), which uses a different adhesive, without alcohol, and delivers equivalent amounts of estradiol. Each of the 758 women wore 4 placebo patches during two 96-hour wear periods. The patch locations were evaluated for 72 hours after removal with respect to erythema, oedema, adhesion, ease of system removal, subject discomfort on system removal, and adhesive residue. In the MX group the foIlowi~g variables were signific~tly lower than in the TTS group: mean erythema scores at the 24 hour timepoint (p < 0.001); percentage of subjects with any degree of erythema (p < 0.005); mean adhesion scores (p <: 0.001). The incidence of erythema scores >3 (i.e. moderate to severe) was low for both systems, as was the overall incidence and severity of oedema. Over 90% of women reported no troublesome discomfort upon removaf of either system. In conclusion, Estraderm MX patches show better skin tolerability and stronger adhesion than Estraderm ‘FI’S patches, and offer an alternative, particularly for women who are sensitive to alcohol or experience adhesion difficulties.
F150 CLiNICAL
GROUPING
OF HORMONE THERAPY
REPLACEMENT
J Hutton, S h’lerchko, L Toop, D Moore, L Scatdon and W Bennett, Pharmaceutical Management Agency, P 0 Box 10-254, Wellington, New Zealand.
5.High
In New Zealand (NZ), some hormone replacement therapies (HRTs) have received higher subsidies than others despite similar therapeutic effects. The aim of this study was to determine if the HRTs available in NZ could be grouped to allow more rational dete~ination of subsidies. The literature was researched, and clinicians and drug companies consulted. The resultant analysis showed there is no difference between the therapeutic outcomes of oral HRT and tr~sde~al HRT. Despite considerable individual variability, the therapeutic outcome of HRTs allowed their division into five, rather than three, groups according to the oestrogen dose: Group Oestrogen Type ~oselstrength l.Low Conjugated equine 0.3mg Transdermal oestradiol 25mcg 2.Medium”low Oestradiol valerate Img 17B-oestradiol lmg Conjugated equine 0.625mg 3.Medium Transde~al oestradiol 50mcg 3.9mg Transdermal oestradiol Oestradioi implant 50mg Oestradiol valerate 4.Medium-high 2mg 17B-oestradiol 2nv.s
Conjugated equine Transdermal oestradiol Tr~sde~~ oestradiol Oestradiol implant
1.25mg 100mcg 7.8mg 1OOmg
This grouping should aliow a more rational determination of the public subsidies for HRTs.
Continued
F151
F152
PHARMACOKINETICS OF A NEW ESTRADIOL MATRIX PATCH IN HEALTHY POSTMENOPAUSAL VOLU~EE~S AND SYMPTOMATIC WOMEN
TOLERABILITY AND ADHESION CHARACTERISTICS A NEW MATRIX PATCH (Estr~derm MX 50)
P boiled L Botta’, G Lej%r(;‘t F Ezzd* Ciba-Geigy Basle’, Switzerland and Rueji-Malmaison’, France. The pharmacokinetics (PK) of a new transdermal estradiol (E2) matrix patch, Estrade~ MX, were investigated in healthy postmenopausal volunteers and symptomatic women. E2 was measured in plasma by highly specific RIA. E2 concentrations were corrected for endogenous baseline by subtraction. Bioavailability of E2 from the matrix patch delivering 5Oug E2/day (MX50) was compared to the conventional membrane system, Estraderm TTS 50 (ITSSO), in 34 volunteers at steady state (ss} during a 96 h application (Study A). Mean E2 AUC, (O-96h) [h.pg/mL] was 3678 for MXSO and 3361 for TTSSO, with a 95% CI for the AUC ratio of (0.91, 1.16) . Average plasma levels C,,[pgimL] were 36.9 and 3 I. 1, and mean fluctuation indices (C,,C,“/C,,) were 1.03 and 2.16, respectively. Additional PK data after 12 weeks treatment of symptomatic women were obtained from two clinical trials, one with MXSO (n=49, Study B) and one with MXSO (n=53) and MXIOO (n=47, Study C). Mean E2 levels ]pg/mL] in symptomatic women affer 12 weeks treatment were 36.2 with MXSO (Study B), and 47.9 with MXSO and 103.1 with MXIOQ (Study C). MX50 is bioequivalent to ‘ITS50 for extent of E2 absorption (AUC). Due to differences in patch design and composition (matrix technolo~, lack of ethanok), MX produces less ~uctuating E2 levels and no distinct peak (C,,) . Average E2 concentrations are similar in healthy sub.jects and s~ptomatic women, and E2 levels double from MX50 to MX 100 in a clinical setting. 90
OF
G Della GOD&, RS Berge8, JA Ct&5~‘, CO Dillar$, ‘Ciba-Geigy Corp. NJ; ‘U~NJ, RW Medical School, New Brunswick, NJ; 3Hilltop Research Inc. NJ; Hilltop Research Inc. FL; 4Hilltop Pharmatest Inc.OH, USA. This open label (obse~er-Baird), r~domised, multicen~e study compared skin tolerability and adhesion characteristics of Estraderm TTS 50 (TTS) with a new matrix patch system (Estraderm MX 50), which uses a different adhesive, without alcohol, and delivers equivalent amounts of estradiol. Each of the 758 women wore 4 placebo patches during two 96-hour wear periods. The patch locations were evaluated for 72 hours after removal with respect to erythema, oedema, adhesion, ease of system removal, subject discomfort on system removal, and adhesive residue. In the MX group the foIlowi~g variables were signific~tly lower than in the TTS group: mean erythema scores at the 24 hour timepoint (p < 0.001); percentage of subjects with any degree of erythema (p < 0.005); mean adhesion scores (p <: 0.001). The incidence of erythema scores >3 (i.e. moderate to severe) was low for both systems, as was the overall incidence and severity of oedema. Over 90% of women reported no troublesome discomfort upon removaf of either system. In conclusion, Estraderm MX patches show better skin tolerability and stronger adhesion than Estraderm ‘FI’S patches, and offer an alternative, particularly for women who are sensitive to alcohol or experience adhesion difficulties.