Pastuszak AW, et al. J Clin Pharmacol. 2021;doi:10.1002/jcph.1939.

Pastuszak AW, et al. J Clin Pharmacol. 2021;doi:10.1002/jcph.1939.

Testosterone undecanoate injected at 8-week intervals for men with hypogonadism may reduce fluctuations and increase mean testosterone levels compared with a 10-week dose regimen, according to data from a modeling study.

“The currently approved 10-week dose regimen of testosterone undecanoate maintains a mean testosterone concentration during a dosing interval within the normal range for most patients,” Alexander W. Pastuszak, MD, PhD, assistant professor in the division of urology, department of surgery at the University of Utah School of Medicine, and colleagues wrote in a study published in The Journal of Clinical Pharmacology. “However, individual patient characteristics may negatively impact testosterone levels and trough testosterone levels may decline in some patients by the end of a testosterone undecanoate 10-week dosing interval. This trough level may result in undesirable breakthrough clinical symptoms associated with low testosterone levels. Thus, treatment with a higher testosterone dose or introduction of a testosterone undecanoate regimen with a shorter dosing interval may be appropriate for some patients.”

Researchers developed a population pharmacokinetic simulation model to assess the impact of 750 mg of intramuscular testosterone undecanoate (Aveed, Endo Pharmaceuticals) for men with hypogonadism when given at 8-week vs. 10-week intervals. The model used data from a phase 3, single-arm, open-label study in which men with hypogonadism received 750 mg of testosterone undecanoate at baseline, 4 weeks, and then every 10 weeks for up to 84 weeks. Men weighing at least 65 kg without other testosterone therapy use and with at least four total testosterone concentration values were included. The final model used for the study was a one-compartment model with first-order elimination and first-order absorption of testosterone. The model factored in the time-dependence of testosterone suppression and recovery of testosterone during administration.

Researchers simulated 500 studies matching the size and demographics of 117 men in the original cohort. The model predicted an increase in testosterone exposure with an 8-week regimen compared with a 10-week regimen, with both the mean and last observed testosterone level increasing approximately 11% with the shorter duration. The maximized testosterone concentration increased 5% with the 8-week regimen compared with 10 weeks.

The estimated percentage of participants with a mean testosterone level between 300 ng/dL and 1,000 ng/dL increased from 97.4% with a 10-week regimen to 98.3% with the 8-week regimen. The proportion of men with a latest observed testosterone concentration of greater than 300 ng/mL increased from 66.7% with a 10-week regimen to 76.1% with an 8-week regimen. No significant change was observed in the percentage of those with a maximum testosterone level of greater than 2,500 ng/dL.

“This pharmacokinetic modeling study supports that more frequent administration of testosterone undecanoate may be beneficial for reducing fluctuations in serum testosterone levels and elevating testosterone concentrations at the end of each maintenance dosing interval while maintaining acceptable levels of overall testosterone exposure,” the researchers wrote. “Further clinical evaluation of a testosterone undecanoate 8-week dosing interval as a maintenance regimen will be needed to assess the clinical relevance of these predictions.”

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