Effect of endogenous steroid hormones on 17-alpha-hydroxyprogesterone caproate metabolism.
OBJECTIVE
Plasma concentrations of 17-alpha-hydroxyprogesterone caproate (17-OHPC) vary substantially in pregnant patients who receive an identical dose. Endogenous steroid hormones may alter 17-OHPC metabolism, which contributes to this large variability.


METHODS
Pooled human liver microsomes were incubated with 17-OHPC alone or in combination with progesterone, hydroxyprogesterone, estrone, estradiol, or estriol. High-performance liquid chromatography with ultraviolet detection was used to quantify 17-OHPC.


RESULTS
Under the conditions that were studied, 17-OHPC metabolism was inhibited by 37% by a combination of endogenous steroid hormones. Progesterone alone significantly inhibited 17-OHPC metabolism by 28% (P < .001).


CONCLUSIONS
17-OHPC metabolism is inhibited significantly by endogenous steroids and, in particular, progesterone. This effect may account for some of the large variation in plasma 17-OHPC concentrations that is seen in pregnant patients who receive a fixed dose of medication.
Magee-Womens Hospital, Department of Obstetrics, Gynecology, and Reproductive Sciences, Division of Maternal-Fetal Medicine, Pittsburgh, PA, USA.
Courtney D
CD
Cuppett
Yang
Y
Zhao
Steve
S
Caritis
Shimin
S
Zhang
Wenchen
W
Zhao
Raman
R
Venkataramanan
D000077713:17 alpha-Hydroxyprogesterone Caproate; D004967:Estrogens / Q000494:pharmacology*; D006801:Humans; D006908:Hydroxyprogesterones / Q000378:metabolism / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology*
D004967:Estrogens; D006908:Hydroxyprogesterones; D000077713:17 alpha-Hydroxyprogesterone Caproate; D011374:Progesterone