Pharmacokinetic comparison of three delivery systems for subcutaneous testosterone administration in female mice.

Autor: Hashim PH; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48109, USA., Kinnear HM; Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI 48109, USA; Medical Scientist Training Program, University of Michigan, Ann Arbor, MI 48109, USA., Cruz CD; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48109, USA., Padmanabhan V; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI 48109, USA., Moravek MB; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48109, USA; Division of Reproductive Endocrinology and Infertility, University of Michigan, Ann Arbor, MI 48109, USA; Department of Urology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: mpenderg@umich.edu., Shikanov A; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48109, USA; Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: shikanov@umich.edu.
Jazyk: angličtina
Zdroj: General and comparative endocrinology [Gen Comp Endocrinol] 2022 Oct 01; Vol. 327, pp. 114090. Date of Electronic Publication: 2022 Jun 24.
DOI: 10.1016/j.ygcen.2022.114090
Abstrakt: Transmasculine individuals are often prescribed testosterone (T) for masculinizing hormone therapy. Mouse models mimicking transmasculine T therapy require reliable long-term T administration. The objectives of this study were three-fold, namely, to compare: 1) the release dynamics of three different subcutaneous delivery systems of T enanthate administration (subcutaneous injections, commercially available pellets, and silastic implants) over a 6-week period in postpubertal C57BL/6N mice, 2) to compare the timing for T levels in plasma to return to baseline and cyclicity to resume after cessation of T between injections and pellets, 3) to utilize silastic implants to achieve sustainable increase in T levels utilizing T enanthate and crystalline T. All three modes of T administration resulted in an increase in T levels in plasma. Pharmacokinetic analyses showed a similar overall exposure to T enanthate over 6 weeks (integrated area) for, subcutaneous injection (0.45 mg two times per week and 0.90 mg one time per week), pellet (5 mg 60-day release), and silastic implant (5 mg 21 week) groups. Crystalline T had lower solubility and a decreased integrated area compared to T enanthate, even when implanted at a higher dosage, indicating different pharmacokinetic profiles based on type of T formulation when utilizing the same silastic delivery method. Surgical removal of pellets and silastic tubing led to a quick drop in T levels and resumption of estrous cyclicity, while cessation of injections required a long washout period for T levels to drop and estrous cycles to resume. Sustained elevation in T levels was achieved for at least 21 weeks with silastic implants. As all three delivery methods are able to elevate T levels in female mice for at least 6 weeks, choice of T administration method should be based on outcomes of interest and study design.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: