FIRST-Testosterone

I Brand Name(s) Androderm, AndroGel, Delatestryl, Depandro 100, Depo-Testoster-one, FIRST Testosterone, FIRST-Testosterone MC, Striant, Testim, Testoderm, Testo-derm TTS, Testopel, Testro AQ, Testro-LA. 

Testosterone is metaboHzed by two pathways. One involves oxidation at the 17 position, and the other involves reduction of the A ring double bond and the 3-ketone. Metabohsm by the first pathway occurs in many tissues, including liver, and produces 17-ketosteroids that... 

Oral testosterone products are also available for supplementation. Unfortunately, testosterone has poor oral bioavailability and undergoes extensive first-pass metabolism. Alkylated derivatives such as methyltestosterone and fluoxymesterone have been formulated to compensate for these problems, but this modification makes them considerably more hepatotoxic. This adverse effect makes oral replacement undesirable and this route of administration should not be used. 

An alternative to the oral route is the buccal mucoadhesive system. The Striant buccal system adheres to the inside of the mouth and the testosterone is absorbed through the oral mucosa and delivered to the systemic circulation. There is no first-pass effect, as the liver is bypassed by this route of administration. Patients apply a 30-mg tablet to the upper gum twice daily. The cost is similar to that of the patch or gel. Side effects unique to this dosage form include oral irritation, bitter taste, and gum edema. 

Poly(D,L-lactic acid) (PLA) nanospheres containing testosterone, with a particle size of 450 nm, were first produced by Vanderhoff et al. [83]. Microfluidization produced spherical particles of less than 200 nm with a narrow size distribution [84]. Krause et al. [85] produced PLA nanoparticles of 500 nm using sonication. The polymer and drug, triamcinolone acetonide, were dissolved in chloroform and emulsified, with sonication, for 45 minutes at 15 °C in a gelatin solution. The solvent was evaporated by heating to 40 °C for 45 minutes under continuous stirring. TEM... 

All the stimulating primer effects in mammals analyzed so far share a common hormonal pathway the first measurable event is stimulation of LH-releasing hormone (LHRH) release. This, in turn, stimulates LH levels and leads to increases of estrogens in females and testosterone in males. In females, changes in size and function of uterus and ovaries follow, while males respond... 

Determination of dose-The number of pellets to be implanted depends upon the minimal daily requirement of testosterone propionate determined by a gradual reduction of the amount administered parenterally. The usual ratio is as follows Implant two 75 mg pellets for each 25 mg testosterone propionate required weekly. It has been found that approximately 33% of the material is absorbed in the first month, 25% in the second month, and 17% in the third month. Adequate effect of the pellets ordinarily continues for 3 to 4 months, sometimes as long as 6 months. 

Oral Testosterone is metabolized by the gut and 44% is cleared by the liver in the first pass. The synthetic androgens are less extensively metabolized by the liver and have longer half-lives and are more suitable than testosterone for oral administration. 

Topical gel Absorption of testosterone into the blood continues for the entire 24-hour dosing interval. Serum concentrations approximate the steady-state level by the end of the first 24 hours and are at steady state by... 

Leuprolide is a potent LH-RH agonist for the first several days to a few weeks after initiation of therapy, and therefore, it initially stimulates testicular and ovarian steroidogenesis. Because of this initial stimulation of testosterone production, it is recommended that patients with prostatic cancer be treated concurrently with leuprolide and the antiandrogen flutamide (discussed earlier). Leuprolide is generally well tolerated, with hot flashes being the most common side effect. 

The concomitant intake of grapefruit juice increases the concentration of many drugs (e.g., testosterone, sildenafil) in humans. Such actions appear to be mediated mainly by the suppression of the cytochrome P450 enzyme CYP3A4 in the small intestine. The resultant diminished first-pass metabolism and increased bioavailability can lead to increased drug levels in the blood. Because sildenafil is metabolized by CYP3A and to a... 

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