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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone and Men's Health Articles
Where does hydrolysis of ND occur in the human body after release from an oil depot?
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<blockquote data-quote="madman" data-source="post: 278224" data-attributes="member: 13851"><p>I would say the schematic illustration (post #16/Figure 2B) from the Testosterone Therapy with Subcutaneous Injections: A Safe, Practical and Reasonable Option paper is not an accurate representation.</p><p></p><p>If anything I would say negligible.</p><p></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/trt-with-subcutaneous-testosterone-injections-a-safe-practical-and-reasonable-option.24297/#post-210977[/URL]</p><p></p><p><strong>Subcutaneous vs Intramuscular Routes</strong></p><p></p><p><em>The IM and SC routes present a defined phase of absorption, in which the serum concentration of the drug administered progressively increases to a maximum (Cmax) and then decreases according to its elimination half-life. <strong>For testosterone esters, the time corresponding from administration to the Cmax, i.e., time of maximum concentration (tmax), is determined by the rate at which absorption occurs, since systemic elimination of testosterone is the same regardless of the route of administration. Therefore, the formulation and the injection site influence the speed and magnitude of absorption.</strong></em></p><p><em><strong></strong></em></p><p><em><strong>After IM or SC administration of a testosterone ester, absorption occurs first by diffusion from the depot into the interstitium (Figure 2B). </strong>The physiology of the IM and SC milieu determines the patterns of absorption after administration. Molecules smaller than 1 kDa, such as testosterone, are preferentially absorbed by the blood capillaries due to the high rate of filtration and reabsorption of fluid across vascular capillaries (39). <strong>However, the <u>hydrolysis of testosterone esters by tissue esterases is a slow process due to their high lipophilicity, with negligible spontaneous hydrolysis in water</u> (40). This results in some of the esterified testosterone to enter the lymphatics, thus prolonging the secondary absorption phase.</strong></em></p><p><em></em></p><p><em>The interstitial fluid consists of plasma ultrafiltrate and proteins derived from tissue metabolism, and is drained by the lymphatics (41).<strong> Because of their lipophilicity, testosterone esters are unlikely to have significant diffusion into the tissues; they <u>likely associate with small proteins and are drained via the lymphatics into the central circulation, with hydrolysis of these esters likely occurring in the central circulation</u> (40).</strong> Therefore, pharmacokinetics of testosterone esters administered via IM versus SC route will vary according to the lymphatic circulation of the tissue. Lymphatic drainage is dependent on intrinsic and extrinsic pumping. Intrinsic pumping is dependent on the contraction of lymphangions (muscular unit of the lymphatics with unidirectional valves) that transport lymph by mechanisms analogous to that occurring in the cardiac chambers (42). Extrinsic pumping results from intermittent external pressure exerted by skeletal muscle contractions on the lymphatics (42). As the lymphatic drainage from SC tissue is largely dependent on intrinsic pumping, while IM lymphatic flow is also substantially influenced by extrinsic pumping during physical activity (43), these drainage patterns suggest that testosterone esters administered SC likely have more stable absorption kinetics compared to IM administration.</em></p><p><em></em></p><p><em>Similar to lymphatics, the hemorheological differences of the vascular compartments of the SC and IM tissues play a role in the pharmacokinetics of testosterone esters. As different muscle groups have variable blood flow (e.g. the blood flow to the deltoids is higher than the glutei) (44), which further varies with physical activity (45), serum on-treatment testosterone concentrations after IM injections are dependent on these characteristics. To the contrary, after SC administration, the drug is delivered to the hypodermis (adipose tissue underlying the dermis), which is not only less vascularized compared to skeletal muscles, but the flow in this region does not increase significantly with physical activity. Since the blood flow at the site of drug administration influences the pharmacokinetics of the administered drug, SC injections display a more stable vascular absorption patterns compared to IM injection</em></p></blockquote><p></p>
[QUOTE="madman, post: 278224, member: 13851"] I would say the schematic illustration (post #16/Figure 2B) from the Testosterone Therapy with Subcutaneous Injections: A Safe, Practical and Reasonable Option paper is not an accurate representation. If anything I would say negligible. [URL unfurl="true"]https://www.excelmale.com/threads/trt-with-subcutaneous-testosterone-injections-a-safe-practical-and-reasonable-option.24297/#post-210977[/URL] [B]Subcutaneous vs Intramuscular Routes[/B] [I]The IM and SC routes present a defined phase of absorption, in which the serum concentration of the drug administered progressively increases to a maximum (Cmax) and then decreases according to its elimination half-life. [B]For testosterone esters, the time corresponding from administration to the Cmax, i.e., time of maximum concentration (tmax), is determined by the rate at which absorption occurs, since systemic elimination of testosterone is the same regardless of the route of administration. Therefore, the formulation and the injection site influence the speed and magnitude of absorption. After IM or SC administration of a testosterone ester, absorption occurs first by diffusion from the depot into the interstitium (Figure 2B). [/B]The physiology of the IM and SC milieu determines the patterns of absorption after administration. Molecules smaller than 1 kDa, such as testosterone, are preferentially absorbed by the blood capillaries due to the high rate of filtration and reabsorption of fluid across vascular capillaries (39). [B]However, the [U]hydrolysis of testosterone esters by tissue esterases is a slow process due to their high lipophilicity, with negligible spontaneous hydrolysis in water[/U] (40). This results in some of the esterified testosterone to enter the lymphatics, thus prolonging the secondary absorption phase.[/B] The interstitial fluid consists of plasma ultrafiltrate and proteins derived from tissue metabolism, and is drained by the lymphatics (41).[B] Because of their lipophilicity, testosterone esters are unlikely to have significant diffusion into the tissues; they [U]likely associate with small proteins and are drained via the lymphatics into the central circulation, with hydrolysis of these esters likely occurring in the central circulation[/U] (40).[/B] Therefore, pharmacokinetics of testosterone esters administered via IM versus SC route will vary according to the lymphatic circulation of the tissue. Lymphatic drainage is dependent on intrinsic and extrinsic pumping. Intrinsic pumping is dependent on the contraction of lymphangions (muscular unit of the lymphatics with unidirectional valves) that transport lymph by mechanisms analogous to that occurring in the cardiac chambers (42). Extrinsic pumping results from intermittent external pressure exerted by skeletal muscle contractions on the lymphatics (42). As the lymphatic drainage from SC tissue is largely dependent on intrinsic pumping, while IM lymphatic flow is also substantially influenced by extrinsic pumping during physical activity (43), these drainage patterns suggest that testosterone esters administered SC likely have more stable absorption kinetics compared to IM administration. Similar to lymphatics, the hemorheological differences of the vascular compartments of the SC and IM tissues play a role in the pharmacokinetics of testosterone esters. As different muscle groups have variable blood flow (e.g. the blood flow to the deltoids is higher than the glutei) (44), which further varies with physical activity (45), serum on-treatment testosterone concentrations after IM injections are dependent on these characteristics. To the contrary, after SC administration, the drug is delivered to the hypodermis (adipose tissue underlying the dermis), which is not only less vascularized compared to skeletal muscles, but the flow in this region does not increase significantly with physical activity. Since the blood flow at the site of drug administration influences the pharmacokinetics of the administered drug, SC injections display a more stable vascular absorption patterns compared to IM injection[/I] [/QUOTE]
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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone and Men's Health Articles
Where does hydrolysis of ND occur in the human body after release from an oil depot?
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