Pharmacokinetics of Jatenzo (Oral Testosterone Undecanoate)
Jatenzo is an oral testosterone formulation that uses a self-emulsifying drug delivery system with lymphatic absorption, achieving physiologic testosterone levels without evidence of hepatotoxicity. 1
Absorption and Bioavailability
- Jatenzo must be taken with food to optimize absorption through the lymphatic system, bypassing first-pass hepatic metabolism that historically made oral testosterone formulations hepatotoxic 1
- The self-emulsifying drug delivery system enables testosterone undecanoate to be absorbed via intestinal lymphatics rather than portal circulation 1
- Dose adjustments should be based on serum testosterone levels measured 4-6 hours after the morning dose, as this represents the peak concentration window 2
Distribution and Steady-State Kinetics
- Testosterone circulates bound to sex hormone-binding globulin (SHBG) and albumin, with approximately 2-3% existing as free (bioactive) testosterone 3
- Target testosterone levels should be in the mid-normal range (450-600 ng/dL) when monitoring patients on Jatenzo 2
- Unlike intramuscular testosterone injections that peak at 2-5 days and return to baseline by 10-14 days, oral formulations provide more stable day-to-day testosterone levels 2
Metabolism and Elimination
- Approximately 90% of testosterone is excreted in urine as glucuronic acid and sulfuric acid conjugates of testosterone and its metabolites 4
- About 6% is excreted in feces, mostly in unconjugated form 4
- Inactivation occurs primarily in the liver through conversion to inactive metabolites 4
- When Jatenzo is discontinued, serum testosterone concentrations return to approximately baseline within 48-72 hours after the last dose 4
Comparison to Other Formulations
- Transdermal testosterone gel produces more variable absorption with individual subjects exhibiting significant peaks at unpredictable times, whereas patches produce profiles that better mimic circadian patterns 5
- Intramuscular testosterone cypionate or enanthate peaks 2-5 days after injection with return to baseline by days 10-14, creating significant fluctuations in testosterone levels 2
- Oral formulations like Jatenzo avoid the supraphysiologic peaks and subtherapeutic troughs seen with injectable testosterone, potentially reducing cardiovascular risk associated with these fluctuations 2
Clinical Monitoring Requirements
- Testosterone levels should be measured 2-3 months after treatment initiation and after any dose change 2
- Once stable levels are confirmed, monitoring every 6-12 months is typically sufficient 2
- Hematocrit must be monitored regularly, withholding treatment if hematocrit exceeds 54% and considering phlebotomy in high-risk cases 2
- For men over 40 years, PSA levels should be monitored before initiating therapy and periodically during treatment 2
Contraindications Specific to Pharmacokinetic Considerations
- Jatenzo is absolutely contraindicated in men actively seeking fertility, as exogenous testosterone suppresses spermatogenesis regardless of formulation 2
- Hematocrit >54% is an absolute contraindication, as testosterone stimulates erythropoietin production 2
- Recent cardiovascular events within the past 3-6 months warrant delaying initiation due to potential fluid retention and cardiovascular effects 2