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A Detailed Analysis of a Pharmacokinetic Model for Testopel® Implants

Received: 1 September 2022     Accepted: 12 October 2022     Published: 29 October 2022
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Abstract

A novel pharmacokinetic model used to titrate therapy for implantable testosterone pellets (Testopel®) in a clinical patient is presented. The model accurately reflects measurements by the Esoterix Laboratory’s serum testosterone assay. The difference between the model’s predictions and the measured levels were clinically insignificant (mean absolute % difference = 2.9%, mean % difference = 0.40%, SD = 4.6%, n = 9), during the early, development phase of the model, and remained small (mean absolute % difference = 5.2%, mean % difference = -1.3%, SD = 7.7%, n = 13) even when newer data points were included. The model was used to predict the peak (900-1100 ng/dL), trough (>300 ng/dL), and average total serum testosterone levels at steady state. Subsequently, the model was used to alter the treatment regimen to yield a specific average serum testosterone level (“area under the curve” ~600 ng/dL), to keep the serum peak under a target amount (<800 ng/dL), and to keep the serum trough above a certain amount (> 400 ng/dL). Targeted levels were reached by the next cycle of Testopel® therapy. This represents the first time such a close correlation between a predicted and a measured serum testosterone has been shown using any assay. Because of the accuracy of the model, the authors recommend using it to provide a quantitative approach to the initiation and maintenance of Testopel® therapy instead of the traditional, more qualitative trial-and-error technique. Clinicians can now target average, peak, and trough testosterone levels and we can reach those levels by the second cycle of therapy. It is likely the model can be extended to aid treatment with implantable testosterone pellets other than Testopel®. This paper presents a detailed analysis of our pharmacokinetic model and its usage as a clinical aid.

Published in International Journal of Clinical Urology (Volume 6, Issue 2)
DOI 10.11648/j.ijcu.20220602.16
Page(s) 95-113
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2022. Published by Science Publishing Group

Keywords

Testosterone Implant, Implantation, Testopel® Pharmacokinetic Model, Testosterone Supplementation, Total Serum Testosterone, Steady State Levels

References
[1] Baillargeon J, Kuo YF, Westra JR, Urban R, Goodwin J (2018) Testosterone prescribing in the United States, 2002-2016, JAMA - Journal of the American Medical Association, vol. 320, no. 2, pp. 200-202. https://doi.org/10.1001/jama.2018.7999
[2] Araujo AB, Esche GR, Kupelian V, O’Donnell AB, Travison TG, Williams RE, Clark RV, McKinlay JB (2007) Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab.; 92: 4241–4247.
[3] CDC Laboratory/Manufacturer Hormone Standardization (HoSt) Program: Total Testosterone - Participant Protocol (report created December 2012, updated January 2013) https://www.cdc.gov/labstandards/pdf/hs/Testosterone_Protocol.pdf
[4] CDC HoSt Certified Total Testosterone Procedures (updated November 2018) https://www.cdc.gov/labstandards/pdf/hs/CDC_Certified_Testosterone_Procedures-508.pdf
[5] CDC Improving Steroid Hormone Measurements in Patient Care and Research Translation (updated July 6, 2017) https://www.cdc.gov/labstandards/hs_workshop.html
[6] Vesper HW, and Botelho JC (2012) Testosterone. An Overview of CDC’s Standardization Initiative, JUN. 1. 2012, Clinical Laboratory News
[7] McCullough, A. (2014) Curr Sex Health Rep 6: 265. https://doi.org/10.1007/s11930-014-0033-7
[8] Seitman D, Fallon J, Kimmel B (2019) Testosterone therapy with Testopel® and the Esoterix Laboratory assay: a CASE study. Urology case reports. https://doi.org/10.1016/j.eucr.2021.101714
[9] Greenblatt, DJ, Koch-Weser, J (1975) The New England Journal of Medicine, Oct 22, 293:7023-705.
[10] Kaminetsky JC, Moclair B, Hemani M, Sand M (2011) A Phase IV Prospective Evaluation of the Safety and Efficacy of Extended Release Testosterone Pellets for the Treatment of Male Hypogonadism. April Journal of Sexual Medicine 8 (4): 1186-96(ISSN: 1743-6109). DOI:10.1111/j.1743-6109.2010.02196.xs
[11] McCullough AR, Khera M, Goldstein I, Hellstrom WJ, Morgentaler A, Levine LA (2012) A multi-institutional observational study of testosterone levels after testosterone pellet (Testopel®) insertion. J Sex Med. 9 (2): 594-601 (ISSN: 1743-6109)DOI: https://doi.org/10.1111/j.1743-6109.2011.02570.x
[12] Pastuszak AW, Mittakanti H, Liu JS, Khera M (2012) Pharmacokinetic Evaluation and Dosing of Subcutaneous Testosterone Pellets. Journal of Andrology, March 33 (5): 927-37 (ISSN: 1939-4640), DOI: 10.2164/jandrol.111.016295
[13] McMahon CG, Shusterman N, Cohen B. (2017) Pharmacokinetics, Clinical Efficacy, Safety Profile, and Patient-Reported Outcomes in Patients Receiving Subcutaneous Testosterone Pellets 900 mg for Treatment of Symptoms Associated With Androgen Deficiency. J Sex Med 14:883e890 DOI: https://doi.org/10.1016/j.jsxm.2017.04.734
[14] Handelsman DJ, Conway AJ, Boylan LM. (1990) Pharmacokinetics and pharmacodynamics of testosterone pellets in man. J Clin Endocrinol Metab 71: 216–222.
[15] Jockenhövel F, Vogel E, Kreutzer M, Reinhardt W, Lederbogen S, Reinwein D. (1996) Pharmacokinetics and pharmacodynamics of subcutaneous testosterone implants in hypogonadal men. Clin Endocrinol (Oxf) 45: 61–71.
[16] Kelleher S, Turner L, Howe C, Conway AJ, Handelsman DJ. (2004) Testosterone release rate and duration of action of testosterone pellet implants, Clinical Endocrinology, 27 February, https://doi.org/10.1111/j.1365-2265.2004.01994.x
[17] Seftel A. (2007) Testosterone Replacement Therapy for Male Hypogonadism: Part III. Pharmacologic and Clinical Profiles, Monitoring, Safety Issues, and Potential Future Agents. Int J Impot Res. 19 (1): 2-24.
[18] Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, Snyder PJ, Swerdloff RS, Wu FC, Yialamas MA. (2018) Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 103, Issue 5, 1 May, Pages 1715–1744, https://doi.org/10.1210/jc.2018-00229
[19] Jones H (ed) (2008) Testosterone Deficiency in Men, edited by Hugh Jones, Oxford University Press.. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/alliant/detail.action?docID=975596.
[20] Lehtihet M, Arver S, Bartuseviciene I, Pousette Å. (2012) S-testosterone decrease after a mixed meal in healthy men independent of SHBG and gonadotrophin levels. Andrologia. 23 April https://doi.org/10.1111/j.1439-0272.2012.01296.x
[21] Matsumoto AM, Bremner WJ (2004) Serum testosterone assays — accuracy matters, J Clin Endocrinol Metab (89): 520–524.
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[23] Clinical Lab Navigator. (2021) www.clinlabnavigator.com/precision.html
Cite This Article
  • APA Style

    David T. Seitman M. S. BME, M. D., Joe J. Fallon M. D. (2022). A Detailed Analysis of a Pharmacokinetic Model for Testopel® Implants. International Journal of Clinical Urology, 6(2), 95-113. https://doi.org/10.11648/j.ijcu.20220602.16

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    ACS Style

    David T. Seitman M. S. BME; M. D.; Joe J. Fallon M. D. A Detailed Analysis of a Pharmacokinetic Model for Testopel® Implants. Int. J. Clin. Urol. 2022, 6(2), 95-113. doi: 10.11648/j.ijcu.20220602.16

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    AMA Style

    David T. Seitman M. S. BME, M. D., Joe J. Fallon M. D. A Detailed Analysis of a Pharmacokinetic Model for Testopel® Implants. Int J Clin Urol. 2022;6(2):95-113. doi: 10.11648/j.ijcu.20220602.16

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  • @article{10.11648/j.ijcu.20220602.16,
      author = {David T. Seitman M. S. BME and M. D. and Joe J. Fallon M. D.},
      title = {A Detailed Analysis of a Pharmacokinetic Model for Testopel® Implants},
      journal = {International Journal of Clinical Urology},
      volume = {6},
      number = {2},
      pages = {95-113},
      doi = {10.11648/j.ijcu.20220602.16},
      url = {https://doi.org/10.11648/j.ijcu.20220602.16},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcu.20220602.16},
      abstract = {A novel pharmacokinetic model used to titrate therapy for implantable testosterone pellets (Testopel®) in a clinical patient is presented. The model accurately reflects measurements by the Esoterix Laboratory’s serum testosterone assay. The difference between the model’s predictions and the measured levels were clinically insignificant (mean absolute % difference = 2.9%, mean % difference = 0.40%, SD = 4.6%, n = 9), during the early, development phase of the model, and remained small (mean absolute % difference = 5.2%, mean % difference = -1.3%, SD = 7.7%, n = 13) even when newer data points were included. The model was used to predict the peak (900-1100 ng/dL), trough (>300 ng/dL), and average total serum testosterone levels at steady state. Subsequently, the model was used to alter the treatment regimen to yield a specific average serum testosterone level (“area under the curve” ~600 ng/dL), to keep the serum peak under a target amount ( 400 ng/dL). Targeted levels were reached by the next cycle of Testopel® therapy. This represents the first time such a close correlation between a predicted and a measured serum testosterone has been shown using any assay. Because of the accuracy of the model, the authors recommend using it to provide a quantitative approach to the initiation and maintenance of Testopel® therapy instead of the traditional, more qualitative trial-and-error technique. Clinicians can now target average, peak, and trough testosterone levels and we can reach those levels by the second cycle of therapy. It is likely the model can be extended to aid treatment with implantable testosterone pellets other than Testopel®. This paper presents a detailed analysis of our pharmacokinetic model and its usage as a clinical aid.},
     year = {2022}
    }
    

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    AB  - A novel pharmacokinetic model used to titrate therapy for implantable testosterone pellets (Testopel®) in a clinical patient is presented. The model accurately reflects measurements by the Esoterix Laboratory’s serum testosterone assay. The difference between the model’s predictions and the measured levels were clinically insignificant (mean absolute % difference = 2.9%, mean % difference = 0.40%, SD = 4.6%, n = 9), during the early, development phase of the model, and remained small (mean absolute % difference = 5.2%, mean % difference = -1.3%, SD = 7.7%, n = 13) even when newer data points were included. The model was used to predict the peak (900-1100 ng/dL), trough (>300 ng/dL), and average total serum testosterone levels at steady state. Subsequently, the model was used to alter the treatment regimen to yield a specific average serum testosterone level (“area under the curve” ~600 ng/dL), to keep the serum peak under a target amount ( 400 ng/dL). Targeted levels were reached by the next cycle of Testopel® therapy. This represents the first time such a close correlation between a predicted and a measured serum testosterone has been shown using any assay. Because of the accuracy of the model, the authors recommend using it to provide a quantitative approach to the initiation and maintenance of Testopel® therapy instead of the traditional, more qualitative trial-and-error technique. Clinicians can now target average, peak, and trough testosterone levels and we can reach those levels by the second cycle of therapy. It is likely the model can be extended to aid treatment with implantable testosterone pellets other than Testopel®. This paper presents a detailed analysis of our pharmacokinetic model and its usage as a clinical aid.
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Author Information
  • Department of Medicine, Rowan University, Stratford, NJ, United States

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