Testosterone buciclate

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

Clinical data
Other names	Testosterone bucyclate; Testosterone 17β-buciclate; 20 Aet-1; CDB-1781; Testosterone 17β-(trans-4-butylcyclohexyl)carboxylate
Routes of administration	Intramuscular injection
Drug class	Androgen; Anabolic steroid; Androgen ester
Pharmacokinetic data
Bioavailability	Oral: very low Intramuscular: very high
Metabolism	Liver
Elimination half-life	Tea seed oil: 20.9 days (i.m.)[1][2] Castor oil: 33.9 days (i.m.)[1][2]
Excretion	Urine
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	105165-22-8
PubChem CID	114819
ChemSpider	19978531
UNII	39BV4XZ2CW
CompTox Dashboard (EPA)	DTXSID90909371
Chemical and physical data
Formula	C30H46O3
Molar mass	454.695 g·mol^−1
3D model (JSmol)	Interactive image
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

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

Route	Medication	Major brand names	Form	Dosage
Oral	Testosterone^a	–	Tablet	400–800 mg/day (in divided doses)
	Testosterone undecanoate	Andriol, Jatenzo	Capsule	40–80 mg/2–4x day (with meals)
	Methyltestosterone^b	Android, Metandren, Testred	Tablet	10–50 mg/day
	Fluoxymesterone^b	Halotestin, Ora-Testryl, Ultandren	Tablet	5–20 mg/day
	Metandienone^b	Dianabol	Tablet	5–15 mg/day
	Mesterolone^b	Proviron	Tablet	25–150 mg/day
Buccal	Testosterone	Striant	Tablet	30 mg 2x/day
	Methyltestosterone^b	Metandren, Oreton Methyl	Tablet	5–25 mg/day
Sublingual	Testosterone^b	Testoral	Tablet	5–10 mg 1–4x/day
	Methyltestosterone^b	Metandren, Oreton Methyl	Tablet	10–30 mg/day
Intranasal	Testosterone	Natesto	Nasal spray	11 mg 3x/day
Transdermal	Testosterone	AndroGel, Testim, TestoGel	Gel	25–125 mg/day
		Androderm, AndroPatch, TestoPatch	Non-scrotal patch	2.5–15 mg/day
		Testoderm	Scrotal patch	4–6 mg/day
		Axiron	Axillary solution	30–120 mg/day
	Androstanolone (DHT)	Andractim	Gel	100–250 mg/day
Rectal	Testosterone	Rektandron, Testosteron^b	Suppository	40 mg 2–3x/day
Injection (IM or SC)	Testosterone	Andronaq, Sterotate, Virosterone	Aqueous suspension	10–50 mg 2–3x/week
	Testosterone propionate^b	Testoviron	Oil solution	10–50 mg 2–3x/week
	Testosterone enanthate	Delatestryl	Oil solution	50–250 mg 1x/1–4 weeks
		Xyosted	Auto-injector	50–100 mg 1x/week
	Testosterone cypionate	Depo-Testosterone	Oil solution	50–250 mg 1x/1–4 weeks
	Testosterone isobutyrate	Agovirin Depot	Aqueous suspension	50–100 mg 1x/1–2 weeks
	Testosterone phenylacetate^b	Perandren, Androject	Oil solution	50–200 mg 1x/3–5 weeks
	Mixed testosterone esters	Sustanon 100, Sustanon 250	Oil solution	50–250 mg 1x/2–4 weeks
	Testosterone undecanoate	Aveed, Nebido	Oil solution	750–1,000 mg 1x/10–14 weeks
	Testosterone buciclate^a	–	Aqueous suspension	600–1,000 mg 1x/12–20 weeks
Implant	Testosterone	Testopel	Pellet	150–1,200 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 ester	Form	Route	Tmax	t1/2	MRT
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	10 days	4.5 days	8.5 days
Testosterone undecanoate	Tea seed oil solution	Intramuscular injection	13.0 days	20.9 days	34.9 days
Testosterone undecanoate	Castor oil solution	Intramuscular injection	11.4 days	33.9 days	36.0 days
Testosterone buciclate^a	Aqueous suspension	Intramuscular injection	25.8 days	29.5 days	60.0 days
Notes: Testosterone cypionate has similar pharmacokinetics to TE. Footnotes: ^a = Never marketed. Sources: See template.

Parenteral durations of androgens/anabolic steroids

Medication	Form	Major brand names	Duration
Testosterone	Aqueous suspension	Andronaq, Sterotate, Virosterone	2–3 days
Testosterone propionate	Oil solution	Androteston, Perandren, Testoviron	3–4 days
Testosterone phenylpropionate	Oil solution	Testolent	8 days
Testosterone isobutyrate	Aqueous suspension	Agovirin Depot, Perandren M	14 days
Mixed testosterone esters^a	Oil solution	Triolandren	10–20 days
Mixed testosterone esters^b	Oil solution	Testosid Depot	14–20 days
Testosterone enanthate	Oil solution	Delatestryl	14–28 days
Testosterone cypionate	Oil solution	Depovirin	14–28 days
Mixed testosterone esters^c	Oil solution	Sustanon 250	28 days
Testosterone undecanoate	Oil solution	Aveed, Nebido	100 days
Testosterone buciclate^d	Aqueous suspension	20 Aet-1, CDB-1781^e	90–120 days
Nandrolone phenylpropionate	Oil solution	Durabolin	10 days
Nandrolone decanoate	Oil solution	Deca Durabolin	21–28 days
Methandriol	Aqueous suspension	Notandron, Protandren	8 days
Methandriol bisenanthoyl acetate	Oil solution	Notandron Depot	16 days
Metenolone acetate	Oil solution	Primobolan	3 days
Metenolone enanthate	Oil solution	Primobolan Depot	14 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

Androgen	Structure	Ester				Relative mol. weight	Relative T content^b	Duration^c
		Position	Moiety	Type	Length^a			Rank	Group
Testosterone		–	–	–	–	1.00	1.00	11	Short
Testosterone propionate		C17β	Propanoic acid	Straight-chain fatty acid	3	1.19	0.84	10	Short
Testosterone isobutyrate		C17β	Isobutyric acid	Aromatic fatty acid	– (~3)	1.24	0.80	9	Moderate
Testosterone cypionate		C17β	Cyclopentylpropanoic acid	Aromatic fatty acid	– (~6)	1.43	0.70	8	Moderate
Testosterone phenylpropionate		C17β	Phenylpropanoic acid	Aromatic fatty acid	– (~6)	1.46	0.69	7	Moderate
Testosterone isocaproate		C17β	Isohexanoic acid	Branched-chain fatty acid	– (~5)	1.34	0.75	6	Moderate
Testosterone caproate		C17β	Hexanoic acid	Straight-chain fatty acid	6	1.35	0.75	5	Moderate
Testosterone enanthate		C17β	Heptanoic acid	Straight-chain fatty acid	7	1.39	0.72	4	Moderate
Testosterone decanoate		C17β	Decanoic acid	Straight-chain fatty acid	10	1.53	0.65	3	Long
Testosterone undecanoate		C17β	Undecanoic acid	Straight-chain fatty acid	11	1.58	0.63	2	Long
Testosterone buciclate^d		C17β	Bucyclic acid^e	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 also

• List of androgen esters § Testosterone esters
• Polytestosterone phloretin phosphate

References

1. 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. 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. C. Coutifaris; L. Mastroianni (15 August 1997). New Horizons in Reproductive Medicine. CRC Press. pp. 100–. ISBN 978-1-85070-793-6.
4. 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. 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. 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.