testosterone buciclate

{{Short description|Chemical compound}}

{{Drugbox

| Verifiedfields =

| Watchedfields =

| verifiedrevid =

| 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

| image = Testosterone buciclate.svg

| image_class = skin-invert-image

| width = 250px

| image2 = Testosterone buciclate molecule ball.png

| width2 = 250px

| tradename =

| pregnancy_AU =

| pregnancy_US =

| pregnancy_category =

| legal_AU =

| legal_CA =

| legal_UK =

| legal_US =

| legal_status =

| routes_of_administration = Intramuscular injection

| class = Androgen; Anabolic steroid; Androgen ester

| bioavailability = Oral: very low
Intramuscular: very high

| protein_bound =

| metabolism = Liver

| elimination_half-life = Tea seed oil: 20.9 days ({{abbrlink|i.m.|intramuscular injection}})
Castor oil: 33.9 days ({{abbr|i.m.|intramuscular injection}})

| excretion = Urine

| CAS_number_Ref =

| CAS_number = 105165-22-8

| CAS_supplemental =

| ATC_prefix =

| ATC_suffix =

| ATC_supplemental =

| PubChem = 114819

| IUPHAR_ligand =

| DrugBank_Ref =

| DrugBank =

| ChemSpiderID_Ref =

| ChemSpiderID = 19978531

| UNII = 39BV4XZ2CW

| KEGG =

| ChEBI =

| ChEMBL =

| synonyms = Testosterone bucyclate; Testosterone 17β-buciclate; 20 Aet-1; CDB-1781; Testosterone 17β-(trans-4-butylcyclohexyl)carboxylate

| C=30 | H=46 | O=3

| 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

| StdInChI_Ref =

| StdInChI = 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

| StdInChIKey_Ref =

| StdInChIKey = 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.{{cite book| vauthors = Hargreave TB | chapter = Towards male hormonal contraception| veditors = Coutifaris C, Mastroianni L |title=New Horizons in Reproductive Medicine| chapter-url = https://books.google.com/books?id=dmokq_M-gm8C&pg=PA100|date=15 August 1997|publisher=CRC Press|isbn=978-1-85070-793-6|pages=100–}}{{cite book|author=William Llewellyn|title=Anabolics|url=https://books.google.com/books?id=afKLA-6wW0oC|year=2009|publisher=Molecular Nutrition Llc|isbn=978-0967930473|pages=138–140}}{{cite journal | vauthors = Behre HM, Nieschlag E | title = Testosterone buciclate (20 Aet-1) in hypogonadal men: pharmacokinetics and pharmacodynamics of the new long-acting androgen ester | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 75 | issue = 5 | pages = 1204–1210 | date = November 1992 | pmid = 1430080 | doi = 10.1210/jcem.75.5.1430080 }} 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. It was first described in 1986. 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.{{cite book | vauthors = Behre HM | chapter = Testosterone Buciclate | veditors = Bhasin S |title=Pharmacology, Biology, and Clinical Applications of Androgens: Current Status and Future Prospects| chapter-url = https://books.google.com/books?id=hurRyWje4DMC&pg=PA472 |date=13 February 1996|publisher=John Wiley & Sons|isbn=978-0-471-13320-9|pages=472–}} 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.{{cite book | vauthors = Behre HM, Weinbauer GF, Nieschlag E | chapter = Testosterone Buciclate | pages = 471–480 | veditors = Bhasin S, Gabelnick HL, Spieler JM | title = Pharmacology, Biology, and Clinical Applications of Androgens: Current Status and Future Prospects | chapter-url = https://books.google.com/books?id=hurRyWje4DMC&pg=PA471 | date = 13 February 1996 | publisher = John Wiley & Sons | isbn = 978-0-471-13320-9 | quote = 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 [...].}}

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.{{cite book| vauthors = Luetjens CM, Wistuba J, Weinbauer G, Nieschlag E | chapter = The Leydig Cell as a Target for Male Contraception | veditors = Payne AH, Hardy MP |title=The Leydig Cell in Health and Disease | chapter-url= https://books.google.com/books?id=x4ttqKIAOg0C&pg=PA423|date=28 October 2007|publisher=Springer Science & Business Media|isbn=978-1-59745-453-7|pages=423–}}{{cite book| vauthors = Nieschlag E, Behre HM | chapter = Testosterone Therapy | veditors = Nieschlag E, Behre HM, Nieschlag S |title=Andrology: Male Reproductive Health and Dysfunction | chapter-url= https://books.google.com/books?id=mEgckDNkonUC&pg=PA442 |date=13 January 2010|publisher=Springer Science & Business Media|isbn=978-3-540-78355-8|pages=441–446}}{{cite journal | vauthors = Behre HM, Abshagen K, Oettel M, Hübler D, Nieschlag E | title = Intramuscular injection of testosterone undecanoate for the treatment of male hypogonadism: phase I studies | journal = European Journal of Endocrinology | volume = 140 | issue = 5 | pages = 414–419 | date = May 1999 | pmid = 10229906 | doi = 10.1530/eje.0.1400414 | s2cid = 22597244 | citeseerx = 10.1.1.503.1752 }} 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. 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. 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. Testosterone buciclate can maintain testosterone levels in the normal male range for up to 20 weeks with a single intramuscular injection.{{cite book| vauthors = Wang C, Swerdloff RS | chapter = Androgen Pharmacology and Delivery Systems | veditors = Bagatell C, Bremner WJ |title=Androgens in Health and Disease| chapter-url = https://books.google.com/books?id=vDcBCAAAQBAJ&pg=PA146|date=27 May 2003|publisher=Springer Science & Business Media|isbn=978-1-59259-388-0|pages=146–}}

Testosterone buciclate is able to reversibly and completely suppress spermatogenesis in men when used at sufficiently high dosages. 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,{{cite journal | vauthors = Behre HM, Baus S, Kliesch S, Keck C, Simoni M, Nieschlag E | title = Potential of testosterone buciclate for male contraception: endocrine differences between responders and nonresponders | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 80 | issue = 8 | pages = 2394–2403 | date = August 1995 | pmid = 7543113 | doi = 10.1210/jcem.80.8.7543113 }} 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.{{cite book | vauthors = Nieschlag E, Behre HM, Engelmann U, Schwarzer U | chapter = Male Contrabution to Contraception | veditors = Nieschlag E, Behre H |title=Andrology: Male Reproductive Health and Dysfunction|chapter-url=https://books.google.com/books?id=05fsCAAAQBAJ&pg=PA412|date=29 June 2013|publisher=Springer Science & Business Media|isbn=978-3-662-04491-9|pages=316, 412}} 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.{{cite journal | vauthors = Nieschlag E, Kumar N, Sitruk-Ware R | title = 7α-methyl-19-nortestosterone (MENTR): the population council's contribution to research on male contraception and treatment of hypogonadism | journal = Contraception | volume = 87 | issue = 3 | pages = 288–295 | date = March 2013 | pmid = 23063338 | doi = 10.1016/j.contraception.2012.08.036 }}

{{Androgen replacement therapy formulations and dosages used in men}}

{{Pharmacokinetics of testosterone esters}}

{{Parenteral durations of androgens/anabolic steroids}}

{{Structural properties of major testosterone esters}}