Testosterone buciclate

Testosterone buciclate
Clinical data
Other namesTestosterone bucyclate; Testosterone 17β-buciclate; 20 Aet-1; CDB-1781; Testosterone 17β-(trans-4-butylcyclohexyl)carboxylate
Routes of
administration
Intramuscular injection
Drug classAndrogen; Anabolic steroid; Androgen ester
Pharmacokinetic data
BioavailabilityOral: very low
Intramuscular: very high
MetabolismLiver
Elimination half-lifeTea seed oil: 20.9 days (i.m.)[1][2]
Castor oil: 33.9 days (i.m.)[1][2]
ExcretionUrine
Identifiers
IUPAC name
  • [(8R,9S,10R,13S,14S,17S)-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl] 4-butylcyclohexane-1-carboxylate
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC30H46O3
Molar mass454.695 g·mol−1
3D model (JSmol)
SMILES
  • CCCCC1CCC(CC1)C(=O)O[C@H]2CC[C@@H]3[C@@]2(CC[C@H]4[C@H]3CCC5=CC(=O)CC[C@]45C)C
InChI
  • InChI=1S/C30H46O3/c1-4-5-6-20-7-9-21(10-8-20)28(32)33-27-14-13-25-24-12-11-22-19-23(31)15-17-29(22,2)26(24)16-18-30(25,27)3/h19-21,24-27H,4-18H2,1-3H3/t20?,21?,24-,25-,26-,27-,29-,30-/m0/s1
  • Key:ODZDZTOROXGJAV-IRWJKHRASA-N

Testosterone buciclate (developmental code names 20 Aet-1, CDB-1781) is a synthetic, injected anabolic–androgenic steroid (AAS) which was never marketed.[3][4][5] It was developed in collaboration by the Contraceptive Development Branch (CDB) of the National Institute of Child Health and Human Development (NICHD) and the World Health Organization (WHO) in the 1970s and early 1980s for use in androgen replacement therapy for male hypogonadism and as a potential male contraceptive.[3] It was first described in 1986.[4] The medication is an androgen ester – specifically, the C17β buciclate (4-butylcyclohexane-1-carboxylate) ester of testosterone – and is a prodrug of testosterone with a very long duration of action when used as a depot via intramuscular injection.[3][6] Testosterone buciclate is formulated as a microcrystalline aqueous suspension with a defined particle size of at least 75% in the range of 10 to 50 μm.[7]

A single intramuscular injection of testosterone buciclate has been found to produce physiological levels of testosterone within the normal range in hypogonadal men for 3 to 4 months.[3][1][8][9][2] The elimination half-life and mean residence time (average amount of time a single molecule of drug stays in the body) of testosterone buciclate were found to be 29.5 days and 60.0 days, respectively, whereas those of testosterone enanthate in castor oil were only 4.5 days and 8.5 days.[8][9][2] Testosterone buciclate also lasts longer than testosterone undecanoate, which has elimination half-lives and mean residence times of 20.9 days and 34.9 days in tea seed oil and 33.9 days and 36.0 days in castor oil, respectively.[1][9][2] In addition, there is a spike in testosterone levels with testosterone enanthate and testosterone undecanoate that is not seen with testosterone buciclate, with which levels stay highly uniform and decrease very gradually and progressively.[1] Testosterone buciclate can maintain testosterone levels in the normal male range for up to 20 weeks with a single intramuscular injection.[10]

Testosterone buciclate is able to reversibly and completely suppress spermatogenesis in men when used at sufficiently high dosages.[8] As such, the results of clinical studies for use of testosterone buciclate as a male contraceptive were promising, and trials continued as late as 1995,[11] but progress ultimately came to a standstill because the WHO was unable to find an industry partner willing to continue the development of the drug.[1] Because of this, the WHO backed away from testosterone buciclate and focused its research instead on testosterone undecanoate, which is also very long-lasting and has the advantage of having already been marketed and approved for medical use.[12]

Androgen replacement therapy formulations and dosages used in men
RouteMedicationMajor brand namesFormDosage
OralTestosteroneaTablet400–800 mg/day (in divided doses)
Testosterone undecanoateAndriol, JatenzoCapsule40–80 mg/2–4x day (with meals)
MethyltestosteronebAndroid, Metandren, TestredTablet10–50 mg/day
FluoxymesteronebHalotestin, Ora-Testryl, UltandrenTablet5–20 mg/day
MetandienonebDianabolTablet5–15 mg/day
MesterolonebProvironTablet25–150 mg/day
SublingualTestosteronebTestoralTablet5–10 mg 1–4x/day
MethyltestosteronebMetandren, Oreton MethylTablet10–30 mg/day
BuccalTestosteroneStriantTablet30 mg 2x/day
MethyltestosteronebMetandren, Oreton MethylTablet5–25 mg/day
TransdermalTestosteroneAndroGel, Testim, TestoGelGel25–125 mg/day
Androderm, AndroPatch, TestoPatchNon-scrotal patch2.5–15 mg/day
TestodermScrotal patch4–6 mg/day
AxironAxillary solution30–120 mg/day
Androstanolone (DHT)AndractimGel100–250 mg/day
RectalTestosteroneRektandron, TestosteronbSuppository40 mg 2–3x/day
Injection (IM or SC)TestosteroneAndronaq, Sterotate, VirosteroneAqueous suspension10–50 mg 2–3x/week
Testosterone propionatebTestovironOil solution10–50 mg 2–3x/week
Testosterone enanthateDelatestrylOil solution50–250 mg 1x/1–4 weeks
XyostedAuto-injector50–100 mg 1x/week
Testosterone cypionateDepo-TestosteroneOil solution50–250 mg 1x/1–4 weeks
Testosterone isobutyrateAgovirin DepotAqueous suspension50–100 mg 1x/1–2 weeks
Testosterone phenylacetatebPerandren, AndrojectOil solution50–200 mg 1x/3–5 weeks
Mixed testosterone estersSustanon 100, Sustanon 250Oil solution50–250 mg 1x/2–4 weeks
Testosterone undecanoateAveed, NebidoOil solution750–1,000 mg 1x/10–14 weeks
Testosterone buciclateaAqueous suspension600–1,000 mg 1x/12–20 weeks
ImplantTestosteroneTestopelPellet150–1,200 mg/3–6 months
Notes: Men produce about 3 to 11 mg testosterone per day (mean 7 mg/day in young men). Footnotes: a = Never marketed. b = No longer used and/or no longer marketed. Sources: See template.
Pharmacokinetics of testosterone esters
Testosterone esterFormRouteTmaxt1/2MRT
Testosterone undecanoateOil-filled capsulesOral ?1.6 hours3.7 hours
Testosterone propionateOil solutionIntramuscular injection ?0.8 days1.5 days
Testosterone enanthateCastor oil solutionIntramuscular injection10 days4.5 days8.5 days
Testosterone undecanoateTea seed oil solutionIntramuscular injection13.0 days20.9 days34.9 days
Testosterone undecanoateCastor oil solutionIntramuscular injection11.4 days33.9 days36.0 days
Testosterone buciclateaAqueous suspensionIntramuscular injection25.8 days29.5 days60.0 days
Notes: Testosterone cypionate has similar pharmacokinetics to TE. Footnotes: a = Never marketed. Sources: See template.
Parenteral durations of androgens/anabolic steroids
MedicationFormMajor brand namesDuration
TestosteroneAqueous suspensionAndronaq, Sterotate, Virosterone2–3 days
Testosterone propionateOil solutionAndroteston, Perandren, Testoviron3–4 days
Testosterone phenylpropionateOil solutionTestolent8 days
Testosterone isobutyrateAqueous suspensionAgovirin Depot, Perandren M14 days
Mixed testosterone estersaOil solutionTriolandren10–20 days
Mixed testosterone estersbOil solutionTestosid Depot14–20 days
Testosterone enanthateOil solutionDelatestryl14–28 days
Testosterone cypionateOil solutionDepovirin14–28 days
Mixed testosterone esterscOil solutionSustanon 25028 days
Testosterone undecanoateOil solutionAveed, Nebido100 days
Testosterone buciclatedAqueous suspension20 Aet-1, CDB-1781e90–120 days
Nandrolone phenylpropionateOil solutionDurabolin10 days
Nandrolone decanoateOil solutionDeca Durabolin21–28 days
MethandriolAqueous suspensionNotandron, Protandren8 days
Methandriol bisenanthoyl acetateOil solutionNotandron Depot16 days
Metenolone acetateOil solutionPrimobolan3 days
Metenolone enanthateOil solutionPrimobolan Depot14 days
Note: All are via i.m. injection. Footnotes: a = TP, TV, and TUe. b = TP and TKL. c = TP, TPP, TiCa, and TD. d = Studied but never marketed. e = Developmental code names. Sources: See template.
Structural properties of major testosterone esters
AndrogenStructureEsterRelative
mol. weight
Relative
T contentb
logPc
Position(s)Moiet(ies)TypeLengtha
Testosterone1.001.003.0–3.4
Testosterone propionateC17βPropanoic acidStraight-chain fatty acid31.190.843.7–4.9
Testosterone isobutyrateC17βIsobutyric acidAromatic fatty acid– (~3)1.240.804.9–5.3
Testosterone isocaproateC17βIsohexanoic acidBranched-chain fatty acid– (~5)1.340.754.4–6.3
Testosterone caproateC17βHexanoic acidStraight-chain fatty acid61.350.755.8–6.5
Testosterone phenylpropionateC17βPhenylpropanoic acidAromatic fatty acid– (~6)1.460.695.8–6.5
Testosterone cypionateC17βCyclopentylpropanoic acidAromatic fatty acid– (~6)1.430.705.1–7.0
Testosterone enanthateC17βHeptanoic acidStraight-chain fatty acid71.390.723.6–7.0
Testosterone decanoateC17βDecanoic acidStraight-chain fatty acid101.530.656.3–8.6
Testosterone undecanoateC17βUndecanoic acidStraight-chain fatty acid111.580.636.7–9.2
Testosterone buciclatedC17βBucyclic acideAromatic carboxylic acid– (~9)1.580.637.9–8.5
Footnotes: a = Length of ester in carbon atoms for straight-chain fatty acids or approximate length of ester in carbon atoms for aromatic fatty acids. b = Relative testosterone content by weight (i.e., relative androgenic/anabolic potency). c = Experimental or predicted octanol/water partition coefficient (i.e., lipophilicity/hydrophobicity). Retrieved from PubChem, ChemSpider, and DrugBank. d = Never marketed. e = Bucyclic acid = trans-4-Butylcyclohexane-1-carboxylic acid. Sources: See individual articles.

See also

References

  1. 1 2 3 4 5 6 Eberhard Nieschlag; Hermann Behre (29 June 2013). Andrology: Male Reproductive Health and Dysfunction. Springer Science & Business Media. pp. 316, 412. ISBN 978-3-662-04491-9.
  2. 1 2 3 4 5 Behre HM, Abshagen K, Oettel M, Hübler D, Nieschlag E (1999). "Intramuscular injection of testosterone undecanoate for the treatment of male hypogonadism: phase I studies". Eur. J. Endocrinol. 140 (5): 414–9. CiteSeerX 10.1.1.503.1752. doi:10.1530/eje.0.1400414. PMID 10229906.
  3. 1 2 3 4 C. Coutifaris; L. Mastroianni (15 August 1997). New Horizons in Reproductive Medicine. CRC Press. pp. 100–. ISBN 978-1-85070-793-6.
  4. 1 2 William Llewellyn (2009). Anabolics. Molecular Nutrition Llc. pp. 138–140. ISBN 978-0967930473.
  5. Behre HM, Nieschlag E (1992). "Testosterone buciclate (20 Aet-1) in hypogonadal men: pharmacokinetics and pharmacodynamics of the new long-acting androgen ester". J. Clin. Endocrinol. Metab. 75 (5): 1204–10. doi:10.1210/jcem.75.5.1430080. PMID 1430080.
  6. Shalender Bhasin (13 February 1996). Pharmacology, Biology, and Clinical Applications of Androgens: Current Status and Future Prospects. John Wiley & Sons. pp. 472–. ISBN 978-0-471-13320-9.
  7. Hermann M. Behre; Gerhard F. Weinbauer; Eberhard Nieschlag (13 February 1996). "Testosterone Buciclate". In Shalender Bhasin; Henry L. Gabelnick; Jeffrey M. Spieler (eds.). Pharmacology, Biology, and Clinical Applications of Androgens: Current Status and Future Prospects. John Wiley & Sons. pp. 471–480. ISBN 978-0-471-13320-9. Testosterone buciclate is applied intramuscularly as a microcrystalline aqueous suspension. [...] After air milling [...] of crystalline testosterone buciclate to a particle size of at least 75% in the range of 10 - 50 μm, the drug was [...] suspended in sterile, aqueous suspension vehicle [...].
  8. 1 2 3 Anita H. Payne; Matthew P. Hardy (28 October 2007). The Leydig Cell in Health and Disease. Springer Science & Business Media. pp. 423–. ISBN 978-1-59745-453-7.
  9. 1 2 3 Eberhard Nieschlag; Hermann M. Behre; Susan Nieschlag (13 January 2010). Andrology: Male Reproductive Health and Dysfunction. Springer Science & Business Media. pp. 441–446. ISBN 978-3-540-78355-8.
  10. Carrie Bagatell; William J. Bremner (27 May 2003). Androgens in Health and Disease. Springer Science & Business Media. pp. 146–. ISBN 978-1-59259-388-0.
  11. Behre HM, Baus S, Kliesch S, Keck C, Simoni M, Nieschlag E (1995). "Potential of testosterone buciclate for male contraception: endocrine differences between responders and nonresponders". J. Clin. Endocrinol. Metab. 80 (8): 2394–403. doi:10.1210/jcem.80.8.7543113. PMID 7543113.
  12. Nieschlag E, Kumar N, Sitruk-Ware R (2013). "7α-methyl-19-nortestosterone (MENTR): the population council's contribution to research on male contraception and treatment of hypogonadism". Contraception. 87 (3): 288–95. doi:10.1016/j.contraception.2012.08.036. PMID 23063338.
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