In contrast to progesterone, OHPC is not metabolized by traditional steroid-transforming enzymes and instead is metabolized exclusively via oxidation at the caproate side chain by cytochrome P450 enzymes. As such, it is not thought to have the same tissue-specific activation and inactivation patterns that progesterone does nor the same non-genomic actions that progesterone and its metabolites possess.Further clinical research is anticipated to provide additional data to help clarify the issue of safety with OHPC. In any case, it has been recommended by the American College of Obstetricians and Gynecologists that pregnant women treated with OHPC receive counseling about its risks and benefits. Pharmacokinetics
Absorption
In animals, the bioavailability of OHPC with intramuscular injection is nearly 100%, but its oral bioavailability is very low at less than 3%. In women, 70 mg/day oral OHPC has similar endometrial potency as 70 mg/day oral OHPA and 2.5 mg/day oral medroxyprogesterone acetate, indicating that oral OHPC and OHPA have almost 30-fold lower potency than medroxyprogesterone acetate via oral administration. Studies on progestogenic endometrial changes with oral OHPC in women are mixed however, with one finding weak effects with 100 mg/day whereas another found that doses of 250 to 1,000 mg produced no effects. As a result of its low oral potency, OHPC has not been used by the oral route and has instead been administered by intramuscular injection.
After decades of use, Squibb, the manufacturer, voluntarily withdrew the Delalutin product in the United States in 1999. Renewed interest in OHPC in the United States was sparked with a large NIH-sponsored study in 2003 that found that OHPC reduced the risk of premature birth in selected at-risk pregnant women. With follow-up data showing no evidence of harmful effects on the offspring, the FDA approved the medication, as sponsored by KV Pharmaceutical as Makena, as an orphan drug in February 2011 to reduce the risk of premature birth in women prior to 37 weeks gestation with a single fetus who had at least one previous premature birth. Society and culture
Generic names
Hydroxyprogesterone caproate is the generic name of OHPC and its INN, USAN, BANM, and JAN, while hydroxyprogesterone hexanoate was its former BANM.OHPC is often mislabeled as and confused with progesterone and 17α-hydroxyprogesterone. It should also not be confused with hydroxyprogesterone acetate, hydroxyprogesterone heptanoate, or medroxyprogesterone acetate. Brand names
OHPC is marketed throughout the world under a variety of brand names including Proluton, Proluton Depot, and Makena (US), among many others. It was also formerly marketed under brand names including Delalutin, Prodrox, and Hylutin among others, but these formulations have since been discontinued. It has been marketed under the brand names Gravibinon and Injectable No. 1 (or Chinese Injectable No. 1) in combination with estradiol valerate and under the brand name Primosiston in combination with estradiol benzoate. Availability
OHPC is marketed in the United States and throughout Europe, Asia, and Central and South America.