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Testosterone Replacement, Low T, HCG, & Beyond
Blood Test Discussion
SubQ might not doing it for me
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<blockquote data-quote="madman" data-source="post: 142955" data-attributes="member: 13851"><p><strong>NEW INSIGHTS INTO DRUG ABSORPTION FROM OIL DEPOTS </strong></p><p></p><p>This dissertation provides new insights into drug absorption from oil depots. Figure 7.1, which was the assumed model before these new findings, is adapted to Figure 7.2.<strong> Here, it is shown that the released prodrug (ND) is not hydrolysed locally (Chapter 6), but remains unchanged in interstitial fluid. <span style="color: rgb(184, 49, 47)">Here, it is logical to assume that the lipophilic prodrug adheres to small proteins (<40 kDa) and subsequently drained with the interstitial fluid into the lymph vessels</span></strong>. <strong>Alternatively, it cannot be excluded that <span style="color: rgb(184, 49, 47)">small oil droplets might be detached from the main oil depot (Chapter 4) and cleared through the lymph. </span></strong>In both ways, <strong>ND will end up in the final lymph node to enter the vena cava superior to meet blood cells in the central compartment.</strong> <strong><span style="color: rgb(184, 49, 47)">These blood cells will finally </span></strong><span style="color: rgb(0, 0, 0)"><strong>hydrolyse the prodrug compound </strong></span><strong><span style="color: rgb(184, 49, 47)">to nandrolone </span></strong></p><p></p><p>------------------------------------------------------------------------------------------------------</p><p></p><p>[ATTACH=full]7100[/ATTACH]</p><p></p><p></p><p></p><p></p><p></p><p></p><p></p><p></p><p><strong>FUTURE PERSPECTIVES </strong></p><p></p><p>The open ends of the current research have been indicated above. <strong><span style="color: rgb(184, 49, 47)">Both the fate of the oil and the role of the immune system towards drug absorption are still not fully understood. </span>In future research, an option to examine drug release and absorption from an oil depot can be performed with a traceability in vivo study. Ideally, 3 tracers would be integrated in the drug product: 1 in the triglyceride structure of the oil components, 1 in the nandrolone molecule and 1 in the decanoic acid moiety. The distinctiveness between these three tracers and between the tissues must obviously be sufficient enough to determine the three compounds separately.</strong> <strong><span style="color: rgb(184, 49, 47)">The whole process of drug release, hydrolysis and oil digestion could then be followed.</span></strong> Nowadays, traceability studies can be performed for instance with Single-photon emission computed tomography (SPECT) or PET/MRI-scanners. These imaging techniques use respectively isotopes or fluoride-atoms to visualise compounds in situ. Unfortunately, these labeling materials are unsuitable to use in the suggested traceability study, because these materials will alter the physical-chemical properties of either the oil formulation or the prodrug compound. This may change the oil viscosity, drug partition coefficient, spatial distribution in administered tissue or immune response, which may consequently influence the biopharmaceutical aspects of drug absorption from oil depots when these materials are not applied.</p><p></p><p></p><p></p><p></p><p></p><p></p><p></p><p></p><p><strong>CONCLUSIONS </strong></p><p></p><p><strong><span style="color: rgb(184, 49, 47)">It is interesting to realize that drug absorption from an oil depot cannot entirely be described by a simple two phase mass transfer model where concentration gradients, diffusion and partition coefficients would enable the calculation of </span><span style="color: rgb(40, 50, 78)">the expected absorption. </span></strong>It is demonstrated in this dissertation that there is a role of the excipient BOH in yielding an initially high absorption. <strong>The oil depot forms a continuous phase after injection, but will be dispersed and encapsulated at the injection site after some days. <span style="color: rgb(184, 49, 47)">This in turn largely influence the way the prodrug becomes available; after release from the oil depot, it is present in the interstitial fluid which is drained through the lymph into the systemic circulation. </span>Subsequently, the prodrug permeates through the wall of blood cells and is <span style="color: rgb(184, 49, 47)">hydrolysed.</span> </strong>Both the lymph transport and the cell wall permeation take time which is expressed in a lag time. <strong>This lag time is different for each injection site:</strong> <strong><span style="color: rgb(184, 49, 47)">a subcutaneously administered prodrug will enter the systemic circulation via a short path and at a low drainage flow. This results in a short lag time and a slow absorption rate constant of the prodrug.</span></strong> <strong>Deeper administered prodrugs (i.e. intramuscular injections) are suggested to be absorbed via a longer path, but at a higher flow, which results in a longer lag time but a higher absorption rate constant of the prodrug.</strong></p><p></p><p></p><p></p><p></p><p>[ATTACH=full]7098[/ATTACH]</p></blockquote><p></p>
[QUOTE="madman, post: 142955, member: 13851"] [B]NEW INSIGHTS INTO DRUG ABSORPTION FROM OIL DEPOTS [/B] This dissertation provides new insights into drug absorption from oil depots. Figure 7.1, which was the assumed model before these new findings, is adapted to Figure 7.2.[B] Here, it is shown that the released prodrug (ND) is not hydrolysed locally (Chapter 6), but remains unchanged in interstitial fluid. [COLOR=rgb(184, 49, 47)]Here, it is logical to assume that the lipophilic prodrug adheres to small proteins (<40 kDa) and subsequently drained with the interstitial fluid into the lymph vessels[/COLOR][/B]. [B]Alternatively, it cannot be excluded that [COLOR=rgb(184, 49, 47)]small oil droplets might be detached from the main oil depot (Chapter 4) and cleared through the lymph. [/COLOR][/B]In both ways, [B]ND will end up in the final lymph node to enter the vena cava superior to meet blood cells in the central compartment.[/B] [B][COLOR=rgb(184, 49, 47)]These blood cells will finally [/COLOR][/B][COLOR=rgb(0, 0, 0)][B]hydrolyse the prodrug compound [/B][/COLOR][B][COLOR=rgb(184, 49, 47)]to nandrolone [/COLOR][/B] ------------------------------------------------------------------------------------------------------ [ATTACH=full]7100[/ATTACH] [B]FUTURE PERSPECTIVES [/B] The open ends of the current research have been indicated above. [B][COLOR=rgb(184, 49, 47)]Both the fate of the oil and the role of the immune system towards drug absorption are still not fully understood. [/COLOR]In future research, an option to examine drug release and absorption from an oil depot can be performed with a traceability in vivo study. Ideally, 3 tracers would be integrated in the drug product: 1 in the triglyceride structure of the oil components, 1 in the nandrolone molecule and 1 in the decanoic acid moiety. The distinctiveness between these three tracers and between the tissues must obviously be sufficient enough to determine the three compounds separately.[/B] [B][COLOR=rgb(184, 49, 47)]The whole process of drug release, hydrolysis and oil digestion could then be followed.[/COLOR][/B] Nowadays, traceability studies can be performed for instance with Single-photon emission computed tomography (SPECT) or PET/MRI-scanners. These imaging techniques use respectively isotopes or fluoride-atoms to visualise compounds in situ. Unfortunately, these labeling materials are unsuitable to use in the suggested traceability study, because these materials will alter the physical-chemical properties of either the oil formulation or the prodrug compound. This may change the oil viscosity, drug partition coefficient, spatial distribution in administered tissue or immune response, which may consequently influence the biopharmaceutical aspects of drug absorption from oil depots when these materials are not applied. [B]CONCLUSIONS [/B] [B][COLOR=rgb(184, 49, 47)]It is interesting to realize that drug absorption from an oil depot cannot entirely be described by a simple two phase mass transfer model where concentration gradients, diffusion and partition coefficients would enable the calculation of [/COLOR][COLOR=rgb(40, 50, 78)]the expected absorption. [/COLOR][/B]It is demonstrated in this dissertation that there is a role of the excipient BOH in yielding an initially high absorption. [B]The oil depot forms a continuous phase after injection, but will be dispersed and encapsulated at the injection site after some days. [COLOR=rgb(184, 49, 47)]This in turn largely influence the way the prodrug becomes available; after release from the oil depot, it is present in the interstitial fluid which is drained through the lymph into the systemic circulation. [/COLOR]Subsequently, the prodrug permeates through the wall of blood cells and is [COLOR=rgb(184, 49, 47)]hydrolysed.[/COLOR] [/B]Both the lymph transport and the cell wall permeation take time which is expressed in a lag time. [B]This lag time is different for each injection site:[/B] [B][COLOR=rgb(184, 49, 47)]a subcutaneously administered prodrug will enter the systemic circulation via a short path and at a low drainage flow. This results in a short lag time and a slow absorption rate constant of the prodrug.[/COLOR][/B] [B]Deeper administered prodrugs (i.e. intramuscular injections) are suggested to be absorbed via a longer path, but at a higher flow, which results in a longer lag time but a higher absorption rate constant of the prodrug.[/B] [ATTACH=full]7098[/ATTACH] [/QUOTE]
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Testosterone Replacement, Low T, HCG, & Beyond
Blood Test Discussion
SubQ might not doing it for me
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