Pharmacokinetics of hard micronized progesterone capsules via vaginal or oral route compared with soft micronized capsules in healthy postmenopausal women: a randomized open-label clinical study.

Purpose: This study aimed to evaluate the pharmacokinetics of hard micronized progesterone capsules (Yimaxin) via the vaginal or oral route compared with soft micronized progesterone capsules (Utrogestan) in a Chinese population. Methods: A prospective single-center randomized open-label trial was conducted in 16 healthy postmenopausal women. They were randomized into two groups to receive four phases of treatment: vaginal Yimaxin, vaginal Utrogestan, oral Yimaxin, or oral Utrogestan, with different sequences. Results: By the vaginal route, steady-state maximum concentration (C-max) of Yimaxin and Utrogestan was 29.13 +/- 8.09 and 12.30 +/- 1.60 mg/L, time to C-max 9.72 +/- 10.50 and 11.03 +/- 9.62 hours, central compartment volume of distribution 4.26 +/- 1.86 and 10.40 +/- 2.32 L, clearance rate 0.18 +/- 0.05 and 0.38 +/- 0.10 L/h, and AUC 261.42 +/- 74.36 and 116.83 +/- 19.72 h.ng/mL, respectively. By the oral route, C-max of Yimaxin and Utrogestan was 62.97 +/- 40.59 and 169.53 +/- 130.24 mg/L, time to C- (max) was 2.88 +/- 1.35 and 2.06 +/- 1.55 hours, central compartment volume of distribution 132.16 +/- 52.13 and 85.08 +/- 55.07 L, clearance rate 3.43 +/- 1.07 and 2.50 +/- 1.04 L/h, and AUC 274.86 +/- 160.28 and 472.00 +/- 250.54 h.ng/mL, respectively. By the vaginal route, C-max , minimum concentration, AUC(0) (72, )and AUC of Yimaxin were higher than Utrogestan, while by the oral route the C-max , AUC(0) (72), and AUC of Utrogestan were higher than Yimaxin. Conclusion: Pharmacokinetic parameters were different between Yimaxin and Utrogestan on vaginal and oral administration. By the oral route, the metabolism and absorption of Utrogestan was superior to Yimaxin, while by the vaginal route Yimaxin was superior.