Plasma testosterone and androstenedione levels in men were measured after oral administration of free testosterone and testosterone undecanoate. Both androgens were determined by simultaneous, specific radioimmunoassays after separation and isolation by thin layer chromatography. While free unesterified testosterone had no effect on plasma androgen levels, a striking increase of both testosterone and androstenedione levels was noted after administration of testosterone undecanoate, which is otherwise only achieved by parenteral testosterone application. This effect of testosterone undecanoate is probably due to absorption via the lymph rather than via the portal vessels so that peripheral circulation is reached before metabolism in the liver. Testosterone undecanoate promises to be an effective medication for oral androgen replacement.
[3H]-testosterone undecanoate ([3H]TU) was administered orally to 4 patients with a thoracic duct catheter after neck dissection surgery. Appearance of radioactivity in lymph, plasma and urine was measured at different times. Metabolites of TU in these fluids were investigated. Peak levels of radioactivity appeared simultaneously in lymph and plasma (2.5-5 h after administration) while the excretion in urine was highest approximately 2 h after the plasma and lymph peak. The main compounds appearing in the lymph were TU and 5alpha-dihydrotestosterone undecanoate (5alpha-DHTU), but 5beta-DHTU could not be detected. In plasma almost all metabolites were probably conjugated. During the first 24 h approximately 40% of the administered radioactivity was excreted in the urine. The total amount of radioactivity excreted in the urine during the first week was 45-48%. The predominant urinary metabolites were testosterone- and androsterone-glucuronide. The results indicate that TU is metabolized partly in the intestinal wall. The remaining TU and newly-formed 5alpha-DHTU, at least partly, are absorbed via the lymphatic system.
Testosterone undecanoate (TU), either dissolved in arachis oil or as micro-crystal suspension, displays androgenic activity on oral administration to rats in the Hershberger test. The solution in arachis oil is more active than the crystal suspension. When [3H]TU is administered orally to rats, most of it is metabolized in the intestinal wall. The majority of the metabolites probably lose their undecanoate group and are absorbed via the portal vein. The non-metabolized [3H]TU and at least two metabolites are absorbed exclusively via the lymphatic system. One of these metabolites has been identified as 5\g=a\-dihydrotestosterone undecanoate (5\g=a\-DHTU).TU has no harmful effects on the liver of the rabbits on oral administration.It is well known that testosterone is inactive in man on oral administration (Foss 8c Camb 1939) while the widely used orally active androgen methyltestosterone may cause hepatic dysfunction in man: BSP retention (deLorimier et al f965) and jaundice (Werner et al. 1950; Foss 8c Simpson 1959). Foss 8c Simpson (1959) showed that testosterone propionate had no effect on liver function in man on parenteral administration. The present study describes the androgenic activity in rats, the effect on liver function in rabbits and the meta¬ bolism in rats of a new orally active androgen, testosterone undecanoate.
Sixty-three Friesian steers (9 mo old, 257 kg; n = 15 or 16/treatment) were employed in a 2 x 2 factorial to test bovine growth hormone (bGH) and estradiol (Compudose implant). Steers received daily subcutaneous injections of vehicle or bGH (40 micrograms/kg body weight) for 22 wk. Steers were slaughtered 8 wk after the end of bGH treatment (wk 30). Steers had ad libitum access to silage plus a fixed amount (4 to 5.5 kg/d) of concentrate. Average daily gain (ADG) and feed conversion efficiency (FCE) improved (P less than .05) in response both to bGH and to estradiol during wk 0 to 22. Although bGH did not affect ADG or FCE during wk 23 to 30, estradiol improved (P less than .05) them; bGH and estradiol appeared additive (nonsignificant interactions) during wk 0 to 22. At slaughter, estradiol increased (P less than .05) carcass weight and carcass and leg length while decreasing (P less than .05) conformation score and percentage of kidney, knob and channel fat (KHP); bGH decreased (P less than .05) KHP. Although both bGH and estradiol increased (P less than .01) plasma GH, their effects were not additive. Both bGH and estradiol increased (P less than .01) plasma somatomedin-C and decreased (P less than .01) plasma urea nitrogen concentrations; effects were additive. Estradiol, but not bGH, increased (P less than .05) plasma glucose, whereas neither bGH nor estradiol altered plasma creatinine and nonesterified fatty acids. In summary, both bGH and estradiol improved growth and FCE, and their effects appeared to be additive. It is likely that some of their effects were mediated by somatomedin-C.
The pharmacodynamics and enantioselective pharmacokinetics of vedaprofen were studied in six ponies in a two period cross-over study, in which a mild acute inflammatory reaction was induced by carrageenan soaked sponges implanted subcutaneously in the neck. Vedaprofen, administered intravenously at a dosage of 1 mg/kg, produced significant and prolonged inhibition of ex vivo serum thromboxane B2 (TXB2) synthesis and short-lived inhibition of exudate prostaglandin E2 (PGE2) and TXB2 synthesis. Vedaprofen also partially inhibited oedematous swelling and leucocyte infiltration into exudate. Vedaprofen displayed enantioselective pharmacokinetics, plasma concentrations of the R(-) enantiomer exceeding those of S(+) vedaprofen. The plasma concentration ratio, R:S, increased from 69:31 at 5 min to 96:4 at 3 h and plasma mean AUC values were 7524 and 1639 ng x h/mL, respectively. Volume of distribution was greater for S(+) vedaprofen, whilst elimination half-life (t(1/2beta)) and mean residence time were greater for R(-) vedaprofen. The penetration of vedaprofen into inflammatory exudate was also enantioselective. For R(-) and S(+) vedaprofen maximum concentration (Cmax) values were 2950 and 1534 ng/mL, respectively, and corresponding AUC values were 9755 and 4400 ng x h/mL. Vedaprofen was highly protein bound (greater than 99%) in both plasma and exudate. The significance of these data for the therapeutic use of vedaprofen is discussed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.