Strawberry Decreases Intraluminal and Intestinal Wall Hydrolysis of Testosterone Undecanoate
Male hypogonadism is often treated by testosterone (T) replacement therapy such as oral administration of the ester prodrug, testosterone undecanoate (TU). However, the systemic exposure to T following oral TU is very low due to esterase-mediated metabolism, particularly in the small intestine. The...
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doaj-0dad470cbb5e4bcaa0f3c105f4ebc5392021-01-06T00:01:50ZengMDPI AGMolecules1420-30492021-01-012623323310.3390/molecules26010233Strawberry Decreases Intraluminal and Intestinal Wall Hydrolysis of Testosterone UndecanoateAtheer Zgair0Yousaf Dawood1Suhaib M. Ibrahem2Jong Bong Lee3Wanshan Feng4Peter M. Fischer5Pavel Gershkovich6College of Pharmacy, University of Anbar, Ramadi 31001, IraqCollege of Pharmacy, University of Anbar, Ramadi 31001, IraqCollege of Pharmacy, University of Anbar, Ramadi 31001, IraqSchool of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UKSchool of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UKSchool of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UKSchool of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UKMale hypogonadism is often treated by testosterone (T) replacement therapy such as oral administration of the ester prodrug, testosterone undecanoate (TU). However, the systemic exposure to T following oral TU is very low due to esterase-mediated metabolism, particularly in the small intestine. The aim of this work was to examine the esterase-inhibitory effect of natural fruit extract of strawberry (STW) on the intestinal degradation of TU as a potential approach to increasing the oral bioavailability of T. Herein, the hydrolysis of TU was assessed in fasted state simulated intestinal fluid with added esterase activity (FaSSIF/ES) and Caco-2 cell homogenates in the presence of STW extract. It is noteworthy that STW substantially inhibited the degradation of TU in FaSSIF/ES and Caco-2 cell homogenates at concentrations that could be achieved following oral consumption of less than one serving of STW fruit. This can significantly increase the fraction of unhydrolyzed TU in the intestinal lumen as well as in enterocytes. In addition, it was demonstrated that TU has high intestinal lymphatic transport potential as the association of TU with plasma-derived human chylomicrons was in the range of 84%. Therefore, oral co-administration of TU with STW could potentially increase the intestinal stability of TU and consequently the contribution of lymphatically delivered TU to the systemic exposure of T in vivo.https://www.mdpi.com/1420-3049/26/1/233testosterone undecanoateFaSSIFintestinal degradationfirst-pass metabolismstrawberry |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Atheer Zgair Yousaf Dawood Suhaib M. Ibrahem Jong Bong Lee Wanshan Feng Peter M. Fischer Pavel Gershkovich |
spellingShingle |
Atheer Zgair Yousaf Dawood Suhaib M. Ibrahem Jong Bong Lee Wanshan Feng Peter M. Fischer Pavel Gershkovich Strawberry Decreases Intraluminal and Intestinal Wall Hydrolysis of Testosterone Undecanoate Molecules testosterone undecanoate FaSSIF intestinal degradation first-pass metabolism strawberry |
author_facet |
Atheer Zgair Yousaf Dawood Suhaib M. Ibrahem Jong Bong Lee Wanshan Feng Peter M. Fischer Pavel Gershkovich |
author_sort |
Atheer Zgair |
title |
Strawberry Decreases Intraluminal and Intestinal Wall Hydrolysis of Testosterone Undecanoate |
title_short |
Strawberry Decreases Intraluminal and Intestinal Wall Hydrolysis of Testosterone Undecanoate |
title_full |
Strawberry Decreases Intraluminal and Intestinal Wall Hydrolysis of Testosterone Undecanoate |
title_fullStr |
Strawberry Decreases Intraluminal and Intestinal Wall Hydrolysis of Testosterone Undecanoate |
title_full_unstemmed |
Strawberry Decreases Intraluminal and Intestinal Wall Hydrolysis of Testosterone Undecanoate |
title_sort |
strawberry decreases intraluminal and intestinal wall hydrolysis of testosterone undecanoate |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2021-01-01 |
description |
Male hypogonadism is often treated by testosterone (T) replacement therapy such as oral administration of the ester prodrug, testosterone undecanoate (TU). However, the systemic exposure to T following oral TU is very low due to esterase-mediated metabolism, particularly in the small intestine. The aim of this work was to examine the esterase-inhibitory effect of natural fruit extract of strawberry (STW) on the intestinal degradation of TU as a potential approach to increasing the oral bioavailability of T. Herein, the hydrolysis of TU was assessed in fasted state simulated intestinal fluid with added esterase activity (FaSSIF/ES) and Caco-2 cell homogenates in the presence of STW extract. It is noteworthy that STW substantially inhibited the degradation of TU in FaSSIF/ES and Caco-2 cell homogenates at concentrations that could be achieved following oral consumption of less than one serving of STW fruit. This can significantly increase the fraction of unhydrolyzed TU in the intestinal lumen as well as in enterocytes. In addition, it was demonstrated that TU has high intestinal lymphatic transport potential as the association of TU with plasma-derived human chylomicrons was in the range of 84%. Therefore, oral co-administration of TU with STW could potentially increase the intestinal stability of TU and consequently the contribution of lymphatically delivered TU to the systemic exposure of T in vivo. |
topic |
testosterone undecanoate FaSSIF intestinal degradation first-pass metabolism strawberry |
url |
https://www.mdpi.com/1420-3049/26/1/233 |
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