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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone Basics & Questions
TLANDO & TLANDO XR - novel oral prodrugs of testosterone
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<blockquote data-quote="madman" data-source="post: 231958" data-attributes="member: 13851"><p>Dosed twice daily.....not a chance!</p><p></p><p>As I have stated in previous threads that title would go to the transdermal T-patch.</p><p></p><p><strong><em>*Only Androderm®, an evening PA transdermal patch, closely replicates the normal T circadian rhythmicity</em></strong></p><p></p><p></p><p></p><p><a href="https://www.excelmale.com/forum/threads/comparison-of-testosterone-blood-concentrations-from-different-trt-products-versus-normal-diurnal-variations.24117/" target="_blank">Comparison of Testosterone Blood Concentrations from Different TRT Products Versus Normal Diurnal Variations</a></p><p></p><p><strong></strong></p><p><strong>3. PK Profiles of Approved Exogenous T Formulations</strong></p><p><strong></strong></p><p><strong>3.4 Transdermal T patch</strong></p><p></p><p><em>The FDA originally approved ANDRODERM®, 51 a non-scrotal transdermal T patch, in 1995, with the 2.5 mg/day and 5.0 mg/day systems. This method of delivery allows T to be continually absorbed without dose accumulations for 24 hours. 52-56 In a 24-week, multicenter, randomized 1:1, parallel-group study comparing the PK, efficacy, and safety of a transdermal T system with IM TE injections in 66 men with TD, daily application of 2 transdermal T patches (5.0 mg/day total) resulted in morning T levels within the defined normal physiologic range (10.6–35.7 nmol/L, or 306–1,031 ng/dL) in 96% of patients over weeks 2 to 24. 54 At week 16, T Cavg was 17.9 ± 6.1 nmol/L (517 ± 176 ng/dL) compared with 1.9 ± 2.2 nmol/L (55.4 ± 62.8 ng/dL) at baseline. Peak T levels were reached approximately 8.2 hours after application, with a Cmax of 26.5 ± 9.6 nmol/L (765 ± 277 ng/dL). <strong>In 34 men from a multicenter, phase 3 study of a transdermal T patch system for TD, nightly applications of 2 patches (5.0 mg/day) resulted in <u>peak levels occurring in the morning after application and decreasing slowly until system removal, mimicking the circadian patterns reported in healthy, young men</u>.52</strong></em></p><p><em></em></p><p><em>A reduced dosing regimen for either 2.0 mg/day or 4.0 mg/day systems applied nightly was evaluated in an interventional study enrolling 40 men with TD for 4 weeks (Clinicaltrials.gov identifier: NCT01104246). This reduced dosing regimen was approved in 2011, and manufacturer data show that following 28 days of transdermal T application, 97% (34/35) men with TD were able to achieve Cavg within 10.4 to 35.7 nmol/L (300–1,030 ng/dL). 51 Mean Cmax values with 2.0 mg/day and 4.0 mg/day treatment were 22.5 ± 5.0 nmol/L (648 ± 145 ng/dL) and 24.1 ± 5.5 nmol/L (696 ± 158 ng/dL), respectively. <strong>Similar to the 2.5 mg/day and 5.0 mg/day systems, peak T levels occurred 8 hours post-application, mimicking diurnal variation when the patch is applied at night.</strong></em></p><p></p><p></p><p></p><p></p><p><strong>3.8 Oral testosterone undecanoate (TU)</strong></p><p></p><p><em>Historically, oral TTh with non-esterified T has been unsuccessful in delivering physiological T due to first-pass hepatic metabolism; to overcome this, high doses were needed to achieve measurable serum T levels.86 A new, oral TU formulation delivered via a self-emulsifying drug delivery system was developed to promote solubilization and absorption of the lipophilic TU in the gastrointestinal tract, and in March 2019, became the first oral TTh approved by the FDA. In a phase 2 study, 200 mg oral TU administered twice a day resulted in 87% of men achieving average serum T levels within the physiological range (10.4–34.7 nmol/L, or 300–1,000 ng/dL), and none of the men had serum T levels >52 nmol/L (1,500 ng/dL). 87<strong> Peak T levels were reached 4 to 5 hours after administration, and levels steadily decreased to baseline at approximately 12 hours unless a second dose was administered.</strong> As oral TU capsules are recommended to be taken with a meal, serum T levels appear to be modulated by dietary fat content. 88 Cavg and mean Cmax serum T levels were approximately 2-fold higher when 200 mg oral TU was administered with food compared with fasting. 87 Dietary fat was found to affect mean serum T levels achieved with oral TU; meals with higher fat content increased serum T concentrations. In a phase 3 study comparing the efficacy and safety of 237 mg oral TU given twice daily with a once-daily 60 mg topical T solution, 87% (145/166) of men with TD treated with oral TU were able to achieve a mean Cavg within 8.7 to 31.4 nmol/L (252–907 ng/dL), meeting the primary objective.89 At the final study visit on day 105, the mean Cavg was 14.0 nmol/L (403 ng/dL) and Cmax was 34.9 nmol/L (1,008 ng/dL).<strong> As oral TU is given twice daily, there were 2 serum T peaks between 20.8 and 24.3 nmol/L (600 and 700 ng/dL) approximately 4 hours after administration, and 2 sub-therapeutic troughs (<6.9 nmol/L or <200 ng/dL) 12 hours after administration, and a peak-to-trough ratio approaching 4.</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*Daily transdermal gels and solutions, and nasal and oral T products, provide a consistent serum T level within the physiologic range in most patients. The daily dosing frequency of the topical gel products results in a PK profile with a resemblance to that of endogenous T in younger males</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*Men using nasal and oral T products are able to achieve mean serum T levels that are within the normal range, <u>but they experience several T peaks and troughs throughout the day because of the multiple daily dosing regimens required (2 or 3 times/day)</u>. <u>This results in a PK profile that significantly deviates from the endogenous PK profiles of both younger and older patients</u></strong></em></p></blockquote><p></p>
[QUOTE="madman, post: 231958, member: 13851"] Dosed twice daily.....not a chance! As I have stated in previous threads that title would go to the transdermal T-patch. [B][I]*Only Androderm®, an evening PA transdermal patch, closely replicates the normal T circadian rhythmicity[/I][/B] [URL="https://www.excelmale.com/forum/threads/comparison-of-testosterone-blood-concentrations-from-different-trt-products-versus-normal-diurnal-variations.24117/"]Comparison of Testosterone Blood Concentrations from Different TRT Products Versus Normal Diurnal Variations[/URL] [B] 3. PK Profiles of Approved Exogenous T Formulations 3.4 Transdermal T patch[/B] [I]The FDA originally approved ANDRODERM®, 51 a non-scrotal transdermal T patch, in 1995, with the 2.5 mg/day and 5.0 mg/day systems. This method of delivery allows T to be continually absorbed without dose accumulations for 24 hours. 52-56 In a 24-week, multicenter, randomized 1:1, parallel-group study comparing the PK, efficacy, and safety of a transdermal T system with IM TE injections in 66 men with TD, daily application of 2 transdermal T patches (5.0 mg/day total) resulted in morning T levels within the defined normal physiologic range (10.6–35.7 nmol/L, or 306–1,031 ng/dL) in 96% of patients over weeks 2 to 24. 54 At week 16, T Cavg was 17.9 ± 6.1 nmol/L (517 ± 176 ng/dL) compared with 1.9 ± 2.2 nmol/L (55.4 ± 62.8 ng/dL) at baseline. Peak T levels were reached approximately 8.2 hours after application, with a Cmax of 26.5 ± 9.6 nmol/L (765 ± 277 ng/dL). [B]In 34 men from a multicenter, phase 3 study of a transdermal T patch system for TD, nightly applications of 2 patches (5.0 mg/day) resulted in [U]peak levels occurring in the morning after application and decreasing slowly until system removal, mimicking the circadian patterns reported in healthy, young men[/U].52[/B] A reduced dosing regimen for either 2.0 mg/day or 4.0 mg/day systems applied nightly was evaluated in an interventional study enrolling 40 men with TD for 4 weeks (Clinicaltrials.gov identifier: NCT01104246). This reduced dosing regimen was approved in 2011, and manufacturer data show that following 28 days of transdermal T application, 97% (34/35) men with TD were able to achieve Cavg within 10.4 to 35.7 nmol/L (300–1,030 ng/dL). 51 Mean Cmax values with 2.0 mg/day and 4.0 mg/day treatment were 22.5 ± 5.0 nmol/L (648 ± 145 ng/dL) and 24.1 ± 5.5 nmol/L (696 ± 158 ng/dL), respectively. [B]Similar to the 2.5 mg/day and 5.0 mg/day systems, peak T levels occurred 8 hours post-application, mimicking diurnal variation when the patch is applied at night.[/B][/I] [B]3.8 Oral testosterone undecanoate (TU)[/B] [I]Historically, oral TTh with non-esterified T has been unsuccessful in delivering physiological T due to first-pass hepatic metabolism; to overcome this, high doses were needed to achieve measurable serum T levels.86 A new, oral TU formulation delivered via a self-emulsifying drug delivery system was developed to promote solubilization and absorption of the lipophilic TU in the gastrointestinal tract, and in March 2019, became the first oral TTh approved by the FDA. In a phase 2 study, 200 mg oral TU administered twice a day resulted in 87% of men achieving average serum T levels within the physiological range (10.4–34.7 nmol/L, or 300–1,000 ng/dL), and none of the men had serum T levels >52 nmol/L (1,500 ng/dL). 87[B] Peak T levels were reached 4 to 5 hours after administration, and levels steadily decreased to baseline at approximately 12 hours unless a second dose was administered.[/B] As oral TU capsules are recommended to be taken with a meal, serum T levels appear to be modulated by dietary fat content. 88 Cavg and mean Cmax serum T levels were approximately 2-fold higher when 200 mg oral TU was administered with food compared with fasting. 87 Dietary fat was found to affect mean serum T levels achieved with oral TU; meals with higher fat content increased serum T concentrations. In a phase 3 study comparing the efficacy and safety of 237 mg oral TU given twice daily with a once-daily 60 mg topical T solution, 87% (145/166) of men with TD treated with oral TU were able to achieve a mean Cavg within 8.7 to 31.4 nmol/L (252–907 ng/dL), meeting the primary objective.89 At the final study visit on day 105, the mean Cavg was 14.0 nmol/L (403 ng/dL) and Cmax was 34.9 nmol/L (1,008 ng/dL).[B] As oral TU is given twice daily, there were 2 serum T peaks between 20.8 and 24.3 nmol/L (600 and 700 ng/dL) approximately 4 hours after administration, and 2 sub-therapeutic troughs (<6.9 nmol/L or <200 ng/dL) 12 hours after administration, and a peak-to-trough ratio approaching 4. *Daily transdermal gels and solutions, and nasal and oral T products, provide a consistent serum T level within the physiologic range in most patients. The daily dosing frequency of the topical gel products results in a PK profile with a resemblance to that of endogenous T in younger males *Men using nasal and oral T products are able to achieve mean serum T levels that are within the normal range, [U]but they experience several T peaks and troughs throughout the day because of the multiple daily dosing regimens required (2 or 3 times/day)[/U]. [U]This results in a PK profile that significantly deviates from the endogenous PK profiles of both younger and older patients[/U][/B][/I] [/QUOTE]
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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone Basics & Questions
TLANDO & TLANDO XR - novel oral prodrugs of testosterone
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