Lynestrenol phenylpropionate

Lynestrenol phenylpropionate

Clinical data
Other names	LPP; 17α-Ethynylestr-4-en-17β-ol 17β-(3-phenylpropionate); 19-Nor-17α-pregn-4-en-20-yn-17-ol benzenepropanoate
Routes of administration	Intramuscular injection
Drug class	Progestogen; Progestin; Progestogen ester
Identifiers
IUPAC name [(8R,9S,10R,13S,14S,17R)-17-Ethynyl-13-methyl-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl] 3-phenylpropanoate
CAS Number	26490-34-6
Chemical and physical data
Formula	C29H36O2
Molar mass	416.605 g·mol^−1
3D model (JSmol)	Interactive image
SMILES O(C(CCC1C=CC=CC=1)=O)[C@](C#C)1CC[C@]([H])2[C@@]([H])3CCC4=CCCC[C@]4([H])[C@@]3([H])CC[C@@]21C
InChI InChI=1S/C29H36O2/c1-3-29(31-27(30)16-13-21-9-5-4-6-10-21)20-18-26-25-15-14-22-11-7-8-12-23(22)24(25)17-19-28(26,29)2/h1,4-6,9-11,23-26H,7-8,12-20H2,2H3/t23-,24+,25+,26-,28-,29-/m0/s1 Key:JOWUABYPVVAHHK-IISZJVLJSA-N

Lynestrenol phenylpropionate (LPP), also known as ethynylestrenol phenylpropionate, is a progestin and a progestogen ester which was developed for potential use as a progestogen-only injectable contraceptive by Organon but was never marketed.^{[1][2][3][4][5][6][7][8]} It was assessed at doses of 25 to 75 mg in an oil solution once a month by intramuscular injection.^[1][4] LPP was associated with high contraceptive failure at the low dose and with poor cycle control.^[3] The medication was found to produce estrogenic effects in the endometrium in women due to transformation into estrogenic metabolites.^[4]

A single intramuscular injection of 50 to 100 mg LPP in oil solution has been found to have a duration of action of 14 to 30 days in terms of clinical biological effect in the uterus and on body temperature in women.^[9]

LPP has a long biological half-life in rats when given as an intramuscular depot injection; its half-life was similar to that of nandrolone laurate (nandrolone dodecanoate) and was about 2-fold longer than that of nandrolone decanoate, 10-fold longer than that of lynestrenol and nandrolone phenylpropionate, 50-fold longer than that of progesterone, and 430-fold longer than that of nandrolone.^[5][6]

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Parenteral potencies and durations of progestogens^[a]^[b]

Compound	Form	Dose for specific uses (mg)[c]			DOA[d]
		TFD[e]	POICD[f]	CICD[g]
Algestone acetophenide	Oil soln.	–	–	75–150	14–32 d
Gestonorone caproate	Oil soln.	25–50	–	–	8–13 d
Hydroxyprogest. acetate[h]	Aq. susp.	350	–	–	9–16 d
Hydroxyprogest. caproate	Oil soln.	250–500[i]	–	250–500	5–21 d
Medroxyprog. acetate	Aq. susp.	50–100	150	25	14–50+ d
Megestrol acetate	Aq. susp.	–	–	25	>14 d
Norethisterone enanthate	Oil soln.	100–200	200	50	11–52 d
Progesterone	Oil soln.	200[i]	–	–	2–6 d
	Aq. soln.	?	–	–	1–2 d
	Aq. susp.	50–200	–	–	7–14 d
Notes and sources: Sources: [10][11][12][13][14][15][9][16][17][18][19][20][21][22][23][24][25][26][27] All given by intramuscular or subcutaneous injection. Progesterone production during the luteal phase is ~25 (15–50) mg/day. The OIDTooltip ovulation-inhibiting dose of OHPC is 250 to 500 mg/month. Duration of action in days. Usually given for 14 days. Usually dosed every two to three months. Usually dosed once monthly. Never marketed or approved by this route. In divided doses (2 × 125 or 250 mg for OHPC, 10 × 20 mg for P4).

See also

• List of progestogen esters § Esters of 19-nortestosterone derivatives

References

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3. Toppozada M (June 1977). "The clinical use of monthly injectable contraceptive preparations". Obstet Gynecol Surv. 32 (6): 335–47. doi:10.1097/00006254-197706000-00001. PMID 865726.
4. Badawy S, Makhlouf A (1975). "The contraceptive action of lynestrenol phenylpropionate". Adv Plan Parent. 10 (3): 149–53. PMID 789155.
5. van der Vies J (1985). "Implications of basic pharmacology in the therapy with esters of nandrolone". Acta Endocrinol Suppl (Copenh). 271 (3_Suppla): 38–44. doi:10.1530/acta.0.109S0038. PMID 3865480.
6. Van der Vies, J (1969). "Mechanism of action of long-acting hormone preparations". Organorama. 6 (5): 4–8. ISSN 0369-7762. Studies were made with nandrolone phenpropionate (Durabolin), nandrolone decanoate, and 16α-ethylprogesterone in peanut oil injected into the gastrocnemius muscle of rats. The free steroid was much more rapidly resorbed than the esters, explaining the action-prolonging effects obtained with the latter. Generally, resorption rates correlated well with duration of action. Resorption from the muscle was followed by transport to the receptor site in the body, during which time ester hydrolysis may occur, releasing the free steroid. Resorption and hydrolysis take place independently, since plasma with inactivated enzymes (heated to 55°) eluted the compds. from a filter paper strip as rapidly as did normal plasma.
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14. Ufer J (1969). The Principles and Practice of Hormone Therapy in Gynaecology and Obstetrics. de Gruyter. p. 49. ISBN 9783110006148. 17α-Hydroxyprogesterone caproate is a depot progestogen which is entirely free of side actions. The dose required to induce secretory changes in primed endometrium is about 250 mg. per menstrual cycle.
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19. Toppozada MK (April 1994). "Existing once-a-month combined injectable contraceptives". Contraception. 49 (4): 293–301. doi:10.1016/0010-7824(94)90029-9. PMID 8013216.
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24. Chu YH, Li Q, Zhao ZF (April 1986). "Pharmacokinetics of megestrol acetate in women receiving IM injection of estradiol-megestrol long-acting injectable contraceptive". The Chinese Journal of Clinical Pharmacology. The results showed that after injection the concentration of plasma MA increased rapidly. The meantime of peak plasma MA level was 3rd day, there was a linear relationship between log of plasma MA concentration and time (day) after administration in all subjects, elimination phase half-life t1/2β = 14.35 ± 9.1 days.
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