Levonorgestrel butanoate

Levonorgestrel butanoate
Clinical data
Other namesLNG-B; HRP-002; Levonorgestrel 17β-butanoate; 17α-Ethynyl-18-methyl-19-nortestosterone 17β-butanoate; 17α-Ethynyl-18-methylestr-4-en-17β-ol-3-one 17β-butanoate
Routes of
administration
Intramuscular injection
Drug classProgestogen; Progestogen ester
ATC code
  • None
Identifiers
  • [(8R,9S,10R,13S,14S,17R)-13-ethyl-17-ethynyl-3-oxo-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-yl] butanoate
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.081.125
Chemical and physical data
FormulaC25H34O3
Molar mass382.544 g·mol−1
3D model (JSmol)
  • CCCC(=O)O[C@]1(CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=CC(=O)CC[C@H]34)CC)C#C
  • InChI=1S/C25H34O3/c1-4-7-23(27)28-25(6-3)15-13-22-21-10-8-17-16-18(26)9-11-19(17)20(21)12-14-24(22,25)5-2/h3,16,19-22H,4-5,7-15H2,1-2H3/t19-,20+,21+,22-,24-,25-/m0/s1
  • Key:GPKLGCALNRZIDS-AYEDEZQKSA-N

Levonorgestrel butanoate (LNG-B) (developmental code name HRP-002), or levonorgestrel 17β-butanoate, is a steroidal progestin of the 19-nortestosterone group which was developed by the World Health Organization (WHO) in collaboration with the Contraceptive Development Branch (CDB) of the National Institute of Child Health and Human Development as a long-acting injectable contraceptive. It is the C17β butanoate ester of levonorgestrel, and acts as a prodrug of levonorgestrel in the body. The drug is at or beyond the phase III stage of clinical development, but has not been marketed at this time. It was first described in the literature, by the WHO, in 1983, and has been under investigation for potential clinical use since then.

LNG-B has been under investigation as a long-lasting injectable contraceptive for women. A single intramuscular injection of an aqueous suspension of 5 or 10 mg LNG-B has a duration of 3 months, whereas an injection of 50 mg has a duration of 6 months. The drug was also previously tested successfully as a combined injectable contraceptive with estradiol hexahydrobenzoate, but this formulation was never marketed. LNG-B has been tested successfully in combination with testosterone buciclate as a long-lasting injectable contraceptive for men as well.

LNG-B may have several advantages over depot medroxyprogesterone acetate, including the use of much lower comparative dosages, reduced progestogenic side effects like hypogonadism and amenorrhea, and a more rapid return in fertility following discontinuation. The drug has a well-established safety record owing to the use of levonorgestrel as an oral contraceptive since the 1960s.

Parenteral potencies and durations of progestogens
Compound Form Dose for specific uses (mg) DOA
TFD POICD CICD
Algestone acetophenideOil soln.-75–15014–32 d
Gestonorone caproateOil soln.25–508–13 d
Hydroxyprogest. acetateAq. susp.3509–16 d
Hydroxyprogest. caproateOil soln.250–500250–5005–21 d
Medroxyprog. acetateAq. susp.50–1001502514–50+ d
Megestrol acetateAq. susp.-25>14 d
Norethisterone enanthateOil soln.100–2002005011–52 d
ProgesteroneOil soln.2002–6 d
Aq. soln. ?1–2 d
Aq. susp.50–2007–14 d
Notes and sources:
  1. Sources:
  2. All given by intramuscular or subcutaneous injection.
  3. 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.
  4. Duration of action in days.
  5. Usually given for 14 days.
  6. Usually dosed every two to three months.
  7. Usually dosed once monthly.
  8. Never marketed or approved by this route.
  9. 1 2 In divided doses (2 × 125 or 250 mg for OHPC, 10 × 20 mg for P4).