The effect of esterases on 17α-hydroxyprogesterone caproate

Objective: The aim of this investigation is to determine whether 17α-hydroxyprogesterone caproate is hydrolyzed, in vitro, to 17α-hydroxyprogesterone and caproate. Study Design: The in vitro hydrolysis of dual radioactively labeled 17α-hydroxy-[³H] progesterone [¹⁴C] caproate by human plasma, hepatic and placental S9 fractions as well as recombinant esterases was investigated. The formation of [³H]-17α-hydroxyprogesterone and [¹⁴C]-caproate were determined with the use of high-performance liquid chromatography equipped with an online radioactivity detector. The presence and activity of carboxylesterase and butyrylcholinesterase in the human-derived preparations was confirmed by the hydrolysis of their prototypic substrates p-nitrophenyl acetate, p-nitrophenyl butyrate, and butyrylthiocholine, respectively. Results: The aforementioned human-derived preparations hydrolyzed p-nitrophenyl acetate, p-nitrophenyl butyrate, and butyrylthiocholine. However, when 17α-hydroxyprogesterone caproate was incubated with the human-derived preparations under identical experimental conditions neither [³H]-17α-hydroxyprogesterone nor [¹⁴C]-caproate was detected. Conclusion: 17α-hydroxyprogesterone caproate is not hydrolyzed in vitro by the esterase enzymes present in human plasma, liver, preterm, or term placenta.