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Pharmacokinetics Absorption Conjugated estrogens are soluble in water and are well absorbed from the gastrointestinal tract after release from the drug formulation. However, PREMPRO and PREMPHASE contain a formulation of medroxyprogesterone acetate (MPA) that is immediately released and conjugated estrogens that are slowly released over several hours. MPA is well absorbed from the gastrointestinal tract. Table 1 summarizes the mean pharmacokinetic parameters for unconjugated and conjugated estrogens, and medroxyprogesterone acetate following administration of 2 PREMPRO 0.625 mg/ 2.5 mg and 2 PREMPRO 0.625 mg/ 5 mg tablets to healthy postmenopausal women. Text Continues Below
TABLE 1. PHARMACOKINETIC PARAMETERS FOR UNCONJUGATED AND CONJUGATED ESTROGENS (CE) AND MEDROXYPROGESTERONE ACETATE (MPA) DRUG 2 x 0.625 mg CE/ 2. 5 mg MPA
Combination Tablets
2 x 0.625 mg CE/ 5 mg MPA
Combination Tablets
(n= 54) (n= 51) PK Parameter Arithmetic Mean
(% CV)
Cmax (pg/ mL) tmax (h) t1/ 2 (h) AUC
(pgh/ mL)
Cmax (pg/ mL) tmax (h) t1/ 2 (h) AUC
(pgh/ mL) Unconjugated Estrogens
Estrone 175
(23)
7.6
(24)
31.6
(23)
5358
(34)
124
(43)
10
(35)
62.2
(137)
6303
(40) BA* -Estrone 159
(26)
7.6
(24)
16.9
(34)
3313
(40)
104
(49)
10
(35)
26.0
(100)
3136
(51) Equilin 71
(31)
5.8
(34)
9.9
(35)
951
(43)
54
(43)
8.9
(34)
15.5
(53)
1179
(56) PK Parameter Arithmetic Mean
(% CV)
Cmax (ng/ mL) tmax (h) t1/ 2 (h) AUC
(ngh/ mL)
Cmax (ng/ mL) tmax (h) t1/ 2 (h) AUC
(ngh/ mL) Conjugated Estrogens Total Estrone 6. 6
(38)
6.1
(28)
20.7
(34)
116
(59)
6.3
(48)
9.1
(29)
23.6
(36)
151
(42) BA* -Total
Estrone
6.4
(39)
6.1
(28)
15.4
(34)
100
(57)
6.2
(48)
9.1
(29)
20.6
(35)
139
(40) Total Equilin 5. 1
(45)
4.6
(35)
11.4
(25)
50
(70)
4.2
(52)
7.0
(36)
17.2
(131)
72
(50) PK Parameter Arithmetic Mean
(% CV)
Cmax (ng/ mL) tmax (h) t1/ 2 (h) AUC
(ngh/ mL)
Cmax (ng/ mL) tmax (h) t1/ 2 (h) AUC
(ngh/ mL) Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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