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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]

Testosterone buciclate
Testosteronebuciclate structure.png
Testosterone buciclate molecule ball.png
Clinical data
SynonymsTestosterone 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
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC30H46O3
Molar mass454.695 g/mol g·mol−1
3D model (JSmol)

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 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,[10] 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.[11]

Pharmacokinetics of testosterone esters

Testosterone ester Form Route of administration Elimination half-life Mean residence time
Testosterone undecanoate Oil-filled capsules Oral 1.6 hours 3.7 hours
Testosterone propionate Oil solution Intramuscular injection 0.8 days 1.5 days
Testosterone enanthate Castor oil solution Intramuscular injection 4.5 days 8.5 days
Testosterone undecanoate Tea seed oil solution Intramuscular injection 20.9 days 34.9 days
Testosterone undecanoate Castor oil solution Intramuscular injection 33.9 days 36.0 days
Testosterone buciclatea Aqueous suspension Intramuscular injection 29.5 days 60.0 days
Notes: Testosterone cypionate has very similar pharmacokinetics to TE. Footnotes: a = Never marketed. Sources: See template.

Parenteral durations of androgens/anabolic steroids

Compound Brand name(s) Type Duration
Testosterone (aq. susp.) Andronaq, Sterotate, Virosterone Androgen 2–3 days
Testosterone propionate Androteston, Perandren, Testoviron Androgen 3–4 days
Testosterone phenylpropionate Testolent Androgen 8 days
Testosterone isobutyrate (aq. susp.) Agovirin Depot, Perandren M Androgen 14 days
Mixed testosterone estersa Triolandren Androgen 10–20 days
Mixed testosterone estersb Testosid Depot Androgen 14–20 days
Testosterone enanthate Delatestryl Androgen 14–20 days
Testosterone cypionate Depovirin Androgen 14–20 days
Mixed testosterone estersc Sustanon 250 Androgen 28 days
Testosterone undecanoate Aveed, Nebido Androgen 100 days
Testosterone buciclate (aq. susp.)d 20 Aet-1, CDB-1781e Androgen 90–120 days
Nandrolone phenylpropionate Durabolin Anabolic 10 days
Nandrolone decanoate Deca Durabolin Anabolic 21 days
Methandriol (aq. susp.) Notandron, Protandren Androgen 8 days
Methandriol bisenanthoyl acetate Notandron Depot Androgen 16 days
Metenolone acetate Primobolan Anabolic 3 days
Metenolone enanthate Primobolan Depot Anabolic 14 days
Note: All are via i.m. injection of oil solution unless noted otherwise. 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

Androgen Structure Ester Relative
mol. weight
Relative
T contentb
Durationc
Position Moiety Type Lengtha Rank Group
Testosterone
Testosteron.svg
1.00 1.00 11 Short
Testosterone propionate
Testosterone propionate.svg
C17β Propanoic acid Straight-chain fatty acid 3 1.19 0.84 10 Short
Testosterone isobutyrate
Testosterone isobutyrate.svg
C17β Isobutyric acid Aromatic fatty acid – (~3) 1.24 0.80 9 Moderate
Testosterone cypionate
Testosterone cypionate.svg
C17β Cyclopentylpropanoic acid Aromatic fatty acid – (~6) 1.43 0.70 8 Moderate
Testosterone phenylpropionate
Testosterone phenpropionate.svg
C17β Phenylpropanoic acid Aromatic fatty acid – (~6) 1.46 0.69 7 Moderate
Testosterone isocaproate
Testosterone isocaproate.svg
C17β Isohexanoic acid Branched-chain fatty acid – (~5) 1.34 0.75 6 Moderate
Testosterone caproate
Testosterone caproate.svg
C17β Hexanoic acid Straight-chain fatty acid 6 1.35 0.75 5 Moderate
Testosterone enanthate
Testosterone enanthate.svg
C17β Heptanoic acid Straight-chain fatty acid 7 1.39 0.72 4 Moderate
Testosterone decanoate
Testosterone decanoate.svg
C17β Decanoic acid Straight-chain fatty acid 10 1.53 0.65 3 Long
Testosterone undecanoate
Testosterone undecanoate.svg
C17β Undecanoic acid Straight-chain fatty acid 11 1.58 0.63 2 Long
Testosterone buciclated
Testosteronebuciclate structure.png
C17β Bucyclic acide Aromatic carboxylic acid – (~9) 1.58 0.63 1 Long
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 = Duration by intramuscular or subcutaneous injection in oil solution (except TiB and TB, which are in aqueous suspension). d = Never marketed. e = Bucyclic acid = trans-4-Butylcyclohexane-1-carboxylic acid. Sources: See individual articles.

See alsoEdit

ReferencesEdit

  1. ^ a b c d e f 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. ^ a b c d e 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. ^ a b c d C. Coutifaris; L. Mastroianni (15 August 1997). New Horizons in Reproductive Medicine. CRC Press. pp. 100–. ISBN 978-1-85070-793-6.
  4. ^ a b 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. ^ a b c 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. ^ a b c 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. ^ 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.
  11. ^ 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.