### Absorption 

When applied to the buccal mucosa, Striant® slowly releases testosterone, allowing for absorption of testosterone through gum and cheek surfaces that are in contact with the buccal system. Since venous drainage from the mouth is to the superior vena cava, trans-buccal delivery of testosterone circumvents first-pass (hepatic) metabolism. 

Following the initial application of Striant®, the serum testosterone concentration rises to a maximum within 10-12 hours. The mean maximum (C max ) and mean average serum total testosterone concentrations for the 12 hour dosing period (C avg(0-12) ) are within the normal physiologic range. 

Striant® is intended for twice daily dosing. Serum concentrations of testosterone reach steady-state levels after the second dose of twice daily Striant® dosing. Following removal of Striant®, the serum testosterone concentration decreases to a level below the normal range within 2-4 hours. 

With twice-daily repeated dosing, mean pharmacokinetic parameters at steady-state for total testosterone serum concentration were very similar between studies of 7-day and 12-week dosing durations. Mean C avg(0-24) across the studies ranged from 520 to 550 ng/dL and these mean values were within the physiologic range (see Table 1). 

Although no specific food effect study was conducted, pivotal Phase 3 study results showed that consumption of food and beverage did not significantly affect the absorption of testosterone from Striant®. 

The effects of toothbrushing, mouthwashing, chewing gum and alcoholic beverages on the use and absorption of Striant® were not investigated in controlled studies, however, Phase 3 clinical studies permitted patients to do these activities indicating the use of Striant® was not significantly affected by these activities. 

### Distribution

Circulating testosterone is chiefly bound in the serum to sex hormone-binding globulin (SHBG) and albumin. The albumin-bound fraction of testosterone easily dissociates from albumin and is presumed to be bioactive. The portion of testosterone bound to SHBG is not considered biologically active. The amount of SHBG in the serum and the total testosterone level will determine the distribution of bioactive and nonbioactive androgen. SHBG-binding capacity is high in prepubertal children, declines during puberty and adulthood, and increases again during the later decades of life. Approximately 40% of testosterone in plasma is bound to SHBG, 2% remains unbound (free) and the rest is bound to albumin and other proteins. 

### Metabolism

There is considerable variation in the half-life of testosterone as reported in the literature, ranging from ten to 100 minutes. Testosterone is metabolized to various 17-keto steroids through two different pathways, and the major active metabolites are estradiol and dihydrotestosterone (DHT). DHT binds with greater affinity to SHBG than does testosterone. In many tissues the activity of testosterone appears to depend on reduction to DHT, which binds to cytosol receptor proteins. The steroid-receptor complex is transported to the nucleus where it initiates transcription and cellular changes related to androgen action. In reproductive tissues, DHT is further metabolized to 3-alpha and 3-beta androstanediol. 

Mean DHT concentrations increase in parallel with testosterone concentrations during Striant® treatment. After 24 hours of treatment, mean DHT serum concentrations are within normal range. The mean steady-state T/DHT ratio during treatment with Striant® remained within normal limits as determined by the analytical laboratory involved with the clinical trials. These ratios ranged from approximately 9-12. 

### Excretion

About 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic and sulfuric acid conjugates of testosterone and its metabolites; about 6% of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver. 

### Special Populations

No formal studies were conducted comparing the pharmacokinetics of testosterone in different racial groups or in compromised patients with renal or hepatic insufficiencies.