TABLE 3.
Pharmacokinetic parameters for TX-001HR and reference products
| Pharmacokinetic parameter | Untransformed data | ||
| TX-001HRa | Reference 1b,c | Reference 2b,d | |
| Progesterone (n = 62) | |||
| Cmax, ng/mL | 89.2 (149.7) | 72.7 (101.9) | 69.7 (87.1) |
| AUC(0-t), ng h/mL | 120.1 (164.1) | 125.9 (152.3) | 111.6 (113.3) |
| AUC(0-inf), ng h/mL | 131.4 (172.5) | 142.1 (160.5) | 126.6 (117.3) |
| tmax, mean (range), h | 3.0 (0.8-10.0) | 3.0 (1.0-12.0) | 4.0 (0.7-18.0) |
| Kel, h−1 | 0.31 (0.24) | 0.27 (0.19) | 0.28 (0.25) |
| t1/2, he | 4.6 (4.5) | 5.2 (5.0) | 5.0 (4.6) |
| AUC% extrap obs | 4.3 (2.5) | 4.8 (3.8) | 5.2 (4.1) |
| Unconjugated estradiol (n = 62) | |||
| Cmax, pg/mL | 64.8 (51.0) | 69.1 (33.1) | 73.4 (43.4) |
| AUC(0-t), pg h/mL | 1,403.7 (763.8) | 1,508.2 (876.7) | 1,658.3 (976.6) |
| AUC(0-inf), pg h/mL | 2,459.4 (4,498.3) | 2,842.9 (4,582.7) | 2,111.0 (1,175.4) |
| tmax, mean (range), h | 9.0 (0.5-36.0) | 10.0 (0.5-35.1) | 10.0 (0.3-36.6) |
| Kel, h−1 | 0.04 (0.02) | 0.05 (0.04) | 0.05 (0.03) |
| t1/2, he | 31.9 (96.0) | 25.1 (28.8) | 20.9 (12.1) |
| AUC% extrap obs | 22.8 (16.7) | 25.5 (20.3) | 25.0 (16.5) |
| Unconjugated estrone (n = 62) | |||
| Cmax, pg/mL | 426.6 (179.3) | 455.5 (189.5) | 467.2 (207.4) |
| AUC(0-t), pg h/mL | 9,096.1 (4,377.3) | 10,156.0 (5,141.6) | 10,507.4 (5,183.1) |
| AUC(0-inf), pg h/mL | 11,995 (6,679) | 13,446 (8,699) | 14,066.2 (7,563.2) |
| tmax, mean (range), h | 5.5 (0.8-36.0) | 8.0 (1.7-18.0) | 10.0 (1.7-18.0) |
| Kel, h−1 | 0.04 (0.01) | 0.04 (0.02) | 0.04 (0.02) |
| t1/2, he | 20.3 (9.4) | 19.5 (9.8) | 20.8 (9.4) |
| AUC% extrap obs | 21.3 (11.2) | 20.4 (11.1) | 21.9 (11.9) |
| Total estrone (n = 61) | |||
| Cmax, ng/mL | 35.4 (17.1) | 19.9 (7.4) | 19.9 (8.0) |
| AUC(0-t), ng h/mL | 201.8 (94.2) | 182.8 (88.8) | 199.7 (94.4) |
| AUC(0-inf), ng h/mL | 213.2 (104.6) | 193.7 (100.5) | 203.1 (81.5) |
| tmax, mean (range), h | 2.5 (0.7-7.0) | 4.0 (1.3-18.0) | 4.0 (1.3-10.0) |
| Kel, h−1 | 0.08 (0.04) | 0.08 (0.04) | 0.07 (0.02) |
| t1/2, he | 10.4 (4.0) | 9.9 (3.1) | 10.8 (3.7) |
| AUC% extrap obs | 4.5 (3.7) | 4.6 (3.5) | 5.4 (4.0) |
Data are presented as mean (SD) unless otherwise stated.
aThe test product is TX-001HR, which combines 2 mg of 17β-estradiol and 200 mg of progesterone in a single capsule (TherapeuticsMD Inc, Boca Raton, FL).
bThe reference product consists of separate formulations of estradiol (Estrace; estradiol USP tablets 2 mg; Teva Pharmaceuticals, Sellersville, PA) and progesterone (Prometrium; progesterone softgel capsule 200 mg; Catalent Pharma Solutions, St Petersburg, FL) administered together.
cReference 1 refers to the first time the reference product was received.
dReference 2 refers to the second time the reference product was received.
eFor these data, t1/2 reflects estimated half-life based on terminal log-linear data points.