Like the closely related progestins hydroxyprogesterone caproate and 19-norprogesterone, gestonorone caproate shows poor activity orally and must be administered parenterally; specifically, via intramuscular injection. Gestonorone caproate is administered by intramuscular injection, and acts as a long-lasting depot by this route. After an intramuscular injection, gestonorone caproate is completely released from the local depot and is highly bioavailable. A single intramuscular injection of 25 to 50 mg gestonorone caproate in oil solution has been found to have a duration of action of 8 to 13 days in terms of clinical biological effect in the uterus in women. At high doses, the duration of action of gestonorone caproate by intramuscular injection has been found to be at least 21 days. Clinical studies have found gestonorone caproate to be satisfactorily effective as a progestogen when injected once a month, whereas it was poorly effective as an injectable contraceptive when it was injected once every two months.
Following a single intramuscular injection of 200 mg radiolabeled gestonorone caproate in 1 mL of solution in men with prostate cancer, maximal levels of gestonorone caproate occurred after 3 ± 1 days and were 420 ± 160 ng/mL. The elimination half-life of gestonorone caproate and its metabolites was 7.5 ± 3.1 days. Approximately 5% of the radioactive steroid content in the blood was unchanged gestonorone caproate. No free gestonorone was observed in circulation or in urine. Gestonorone caproate and its metabolites were eliminated 72% in feces and 28% in urine. Approximately 48 ± 18% of the injected dose had been eliminated after 14 days and approximately 85 ± 12% of the injected dose had been excreted after 30 days.
The metabolism of unesterified gestonorone (17α-hydroxy-19-norprogesterone) is analogous to that of 17α-hydroxyprogesterone, with the corresponding 19-norpregnane metabolites produced. Gestonorone caproate has been found to undergo 5α-reduction similarly to progesterone, 17α-hydroxyprogesterone, and gestonorone, and at a similar rate as these steroids. Conversely however, due to its caproate ester, 5β-reduction of gestonorone caproate is decreased relative to these steroids. As progesterone is metabolized mainly into 5β-pregnanes, decreased 5β-reduction of gestonorone caproate may be involved in its greater potency compared to progesterone. The major metabolites of gestonorone caproate have been reported to be isomers of 19-norpregnanetriol and 19-norpregnanediol-20-one. These metabolites indicate that gestonorone caproate is metabolized mainly by reduction at the C3, C5, and C20 positions. Following an intramuscular injection of 300 mg gestonorone caproate, only a slight increase in urinary pregnanetriol excretion has been observed. Cleavage of the caproate ester of gestonorone caproate is minimal, which indicates that it is not a prodrug of the unesterified steroid.