Oral testosterone-triglyceride conjugate in rabbits: single-dose pharmacokinetics and comparison with oral testosterone undecanoate

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Oral testosterone-triglyceride conjugate in rabbits: single-dose pharmacokinetics and comparison with oral testosterone undecanoate

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dc.contributor.author Amory, D. W. en_US
dc.contributor.author Bremner, William J. en_US
dc.contributor.author Amory, John K. en_US
dc.contributor.author Scriba, G. K. E. en_US
dc.date.accessioned 2008-10-17T20:41:56Z
dc.date.available 2008-10-17T20:41:56Z
dc.date.issued 2003-09 en_US
dc.identifier.citation J Androl. 2003 Sep-Oct;24(5):716-20 en_US
dc.identifier.uri http://hdl.handle.net/1773/4386
dc.description.abstract Development of a safe and effective oral form of testosterone has been inhibited by the rapid hepatic metabolism of nonalkylated androgens. Since triglycerides are absorbed via lymphatics and bypass the liver, we hypothesized that a testosterone-triglyceride conjugate (TTC) might allow for safe and effective oral testosterone therapy. Therefore, we studied the single-dose pharmacokinetics of oral administration of TTC in rabbits. Female New Zealand rabbits were administered 2, 4, or 8 mg/kg of TTC in sesame oil by gastric lavage. Testosterone undecanoate (TU) by gastric lavage was used as a positive control. Blood was sampled from a catheter in the auricular artery at 0, 15, 30, 60, 90, 120, 180, 240, 360, 480, and 600 minutes after drug administration. Samples were assayed for testosterone by a fluoroimmunoassay. Mean serum testosterone, area under the curve (AUC), and terminal half-life were calculated. Oral TTC administration resulted in rapid and marked increases in serum testosterone. Oral TTC resulted in higher maximum serum testosterone concentrations than oral TU at 8 mg/kg (TTC: 28.6 +/- 7.9 nmol/L vs TU: 11.9 +/- 2.1 nmol/L; P <.001) and 4 mg/kg (TTC: 11.5 +/- 4.2 nmol/L vs TU: 3.6 +/- 1.0 nmol/L; P <.001). In addition, the AUC was 1.8 to 2.6 times greater for TTC than TU at both doses (P <.05). The terminal half-life for both TU and TTC was between 3 and 5 hours and was not significantly different. We conclude that oral TTC is rapidly absorbed from the rabbit intestine and results in elevated concentrations of serum testosterone. The absorption of TTC appears to be superior to that of TU; however, the in vivo persistence of the 2 compounds is similar. TTC may offer an alternative to the use of TU for oral testosterone therapy. Further testing of this compound is warranted. en_US
dc.language.iso en_US en_US
dc.publisher American Society of Andrology en_US
dc.subject hypogonadism en_US
dc.subject androgen en_US
dc.subject lymphatics en_US
dc.subject.mesh Triglycerides, blood, chemistry, pharmacokinetics en_US
dc.subject.mesh Male en_US
dc.subject.mesh Testosterone, analogs & derivatives, blood, chemistry, pharmacokinetics en_US
dc.subject.mesh Animals en_US
dc.subject.mesh Rabbits en_US
dc.subject.mesh Research Support, U.S. Gov't, P.H.S. en_US
dc.subject.mesh Androgens, blood, chemistry, pharmacokinetics en_US
dc.subject.mesh Models, Animal en_US
dc.subject.mesh Administration, Oral en_US
dc.subject.mesh Comparative Study en_US
dc.subject.mesh Hypogonadism, drug therapy en_US
dc.title Oral testosterone-triglyceride conjugate in rabbits: single-dose pharmacokinetics and comparison with oral testosterone undecanoate en_US
dc.type Article en_US


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