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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone Basics & Questions
Official Natesto Thread
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<blockquote data-quote="madman" data-source="post: 217754" data-attributes="member: 13851"><p>[URL unfurl="true"]https://www.excelmale.com/forum/threads/pk-of-tth-and-diurnal-variation-of-testosterone.24117/[/URL]</p><p></p><p></p><p><strong>3.6 Nasal administration</strong></p><p></p><p><em>Approved by the FDA in May 2014, the nasal gel formulation of TTh (NATESTO® ) is a product using a metered-dose pump delivering 5.5 mg of T per pump actuation, with the recommended dosing of 2 pumps (11 mg; 1 actuation/nostril) administered intranasally 3 times daily (total 33 mg/day) 6 to 8 hours apart.77 Absorption occurs through the nasal mucosa, thereby avoiding hepatic first-pass metabolism, with approximately 75% of administered T entering the blood.78 <strong>Peak serum T levels were reached approximately 60 minutes post-application and declined to near baseline before the next dose. 79,80</strong> In a randomized, dose-ranging, open-label phase 3 study of 306 men with TD (ClinicalTrials.gov NCT01446042), 11 mg nasal T dosed two times or three times daily resulted in between 71% and 91% of patients achieving serum TT concentrations within the defined range (10.4– 36.4 nmol/L; 300–1,050 ng/dL). At day 90, mean TT Cavg values were 13.0 and 14.6 nmol/L (375 and 421 ng/dL) for 11 mg dosed two or three times daily, respectively. 79<strong> Compared with other routes of T delivery, nasal T gel administration results in rather low Cavg and Cmax TT levels, as well as DHT and DHT: T ratios, even with administering 11 mg three times daily. </strong>While patients experience 3 Cmax peaks in one day because of the required 3 daily doses, only 3.3% of patients had a Cmax between 62.4 and 86.7 nmol/L (1,800–2,500 ng/dL). At day 90, the Cmax and Cmin were 32.4 nmol/L (934.9 ng/dL) and 7.0 nmol/L (200.9 ng/dL), respectively, with a peak-to-trough ratio of 4.7. <strong>Furthermore, an ongoing phase 4 clinical trial suggests that not only can T nasal gel increases serum T over time, but it can also maintain FSH, LH, and semen parameters. 81</strong></em></p><p></p><p></p><p></p><p></p><p><strong>Figure 1. <u>Extrapolated mean steady-state serum total testosterone concentrations</u>. Estimated diurnal T in <u>young men</u> (<u>blue</u>, age range: 23-28 years) and <u>older men</u> (<u>yellow</u>, age range 58- 82 years). <u>Red arrows</u> indicate the time of T administration. <u>Dotted lines</u> indicate Cavg over the dosing interval of 168 hours. <u>Black lines</u> in each panel represent mean steady-state T profiles of </strong><u>A</u>) weekly SC TE administration;<u> B</u>) average mean T profiles for IM TC, TE, and TU over 2 weeks; <u>C</u>) 900 mg subdermal T pellets; D) 4.0 mg daily transdermal patch; E) average mean T profiles of 100 mg TESTIM® /VOGELXO®, 40 mg FORTESTA®, 1.62% AndroGel®, and 2% AXIRON®; <strong>F) nasal gel T at day 90 three times daily; </strong>G) 30 mg buccal mucoadhesives applied twice daily, and H) twice daily 200 mg oral TU capsules.</p><p></p><p><strong>*For products with ≥1 daily dose, we extrapolated data over 1 week to compare all PK profiles consistently. For products with dosing regimens of longer than a week (eg, IM injections and T pellet implantation), only the PK profile in the first week following dosing is presented; these data do not reflect average concentrations throughout the entire dosing interval.</strong></p><p><strong></strong></p><p><strong>IM, intramuscular; SC, subcutaneous; T, testosterone; TC, testosterone cypionate; TE, testosterone enanthate; TU, testosterone undecanoate.</strong></p><p><strong></strong></p><p><strong></strong></p><p><strong>F. nasal gel</strong></p><p><em><strong>[ATTACH=full]19792[/ATTACH]</strong></em></p></blockquote><p></p>
[QUOTE="madman, post: 217754, member: 13851"] [URL unfurl="true"]https://www.excelmale.com/forum/threads/pk-of-tth-and-diurnal-variation-of-testosterone.24117/[/URL] [B]3.6 Nasal administration[/B] [I]Approved by the FDA in May 2014, the nasal gel formulation of TTh (NATESTO® ) is a product using a metered-dose pump delivering 5.5 mg of T per pump actuation, with the recommended dosing of 2 pumps (11 mg; 1 actuation/nostril) administered intranasally 3 times daily (total 33 mg/day) 6 to 8 hours apart.77 Absorption occurs through the nasal mucosa, thereby avoiding hepatic first-pass metabolism, with approximately 75% of administered T entering the blood.78 [B]Peak serum T levels were reached approximately 60 minutes post-application and declined to near baseline before the next dose. 79,80[/B] In a randomized, dose-ranging, open-label phase 3 study of 306 men with TD (ClinicalTrials.gov NCT01446042), 11 mg nasal T dosed two times or three times daily resulted in between 71% and 91% of patients achieving serum TT concentrations within the defined range (10.4– 36.4 nmol/L; 300–1,050 ng/dL). At day 90, mean TT Cavg values were 13.0 and 14.6 nmol/L (375 and 421 ng/dL) for 11 mg dosed two or three times daily, respectively. 79[B] Compared with other routes of T delivery, nasal T gel administration results in rather low Cavg and Cmax TT levels, as well as DHT and DHT: T ratios, even with administering 11 mg three times daily. [/B]While patients experience 3 Cmax peaks in one day because of the required 3 daily doses, only 3.3% of patients had a Cmax between 62.4 and 86.7 nmol/L (1,800–2,500 ng/dL). At day 90, the Cmax and Cmin were 32.4 nmol/L (934.9 ng/dL) and 7.0 nmol/L (200.9 ng/dL), respectively, with a peak-to-trough ratio of 4.7. [B]Furthermore, an ongoing phase 4 clinical trial suggests that not only can T nasal gel increases serum T over time, but it can also maintain FSH, LH, and semen parameters. 81[/B][/I] [B]Figure 1. [U]Extrapolated mean steady-state serum total testosterone concentrations[/U]. Estimated diurnal T in [U]young men[/U] ([U]blue[/U], age range: 23-28 years) and [U]older men[/U] ([U]yellow[/U], age range 58- 82 years). [U]Red arrows[/U] indicate the time of T administration. [U]Dotted lines[/U] indicate Cavg over the dosing interval of 168 hours. [U]Black lines[/U] in each panel represent mean steady-state T profiles of [/B][U]A[/U]) weekly SC TE administration;[U] B[/U]) average mean T profiles for IM TC, TE, and TU over 2 weeks; [U]C[/U]) 900 mg subdermal T pellets; D) 4.0 mg daily transdermal patch; E) average mean T profiles of 100 mg TESTIM® /VOGELXO®, 40 mg FORTESTA®, 1.62% AndroGel®, and 2% AXIRON®; [B]F) nasal gel T at day 90 three times daily; [/B]G) 30 mg buccal mucoadhesives applied twice daily, and H) twice daily 200 mg oral TU capsules. [B]*For products with ≥1 daily dose, we extrapolated data over 1 week to compare all PK profiles consistently. For products with dosing regimens of longer than a week (eg, IM injections and T pellet implantation), only the PK profile in the first week following dosing is presented; these data do not reflect average concentrations throughout the entire dosing interval. IM, intramuscular; SC, subcutaneous; T, testosterone; TC, testosterone cypionate; TE, testosterone enanthate; TU, testosterone undecanoate. F. nasal gel[/B] [I][B][ATTACH type="full" alt="Screenshot (10993).png"]19792[/ATTACH][/B][/I] [/QUOTE]
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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone Basics & Questions
Official Natesto Thread
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